Category Archives: Cell Medicine

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Basel, August 20, 2020 Novartis today announced that the US Food and Drug Administration (FDA) has approved Kesimpta (ofatumumab, formerly OMB157) as an injection for subcutaneous use for the treatment of relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Kesimpta is a targeted, precisely dosed and delivered B-cell therapy that has shown superior efficacy with a similar safety profile compared with teriflunomide and is a first-choice treatment option for RMS patients1. Kesimpta is the first B-cell therapy that can be self-administered once monthly at home via the Sensoready autoinjector pen3.

This approval is wonderful news for patients with relapsing multiple sclerosis. In the key clinical studies, this breakthrough treatment produced a profound reduction in new brain lesions, reducing relapses and slowing underlying disease progression1, said Professor Stephen L. Hauser, Director of the UCSF Weill Institute for Neurosciences and co-chair of the steering committee for the ASCLEPIOS I and II studies. Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center1.

One of the goals when managing RMS is to preserve neurological function to slow down the worsening of disability4. Despite the availability of several disease-modifying therapies (DMTs) for the treatment of RMS, the majority of individuals with RMS continue to experience disease activity5. Evidence suggests early initiation of high-efficacy treatment can improve long-term outcomes for patients with RMS6.

Multiple sclerosis (MS) is a complex disease, and response to disease modifying treatment will vary among individuals, said Bruce Bebo, PhD, Executive Vice President of Research at the National MS Society. This makes it important to have a range of treatments available with different mechanisms of action and routes of administration. We are pleased to have an additional option approved for the treatment of relapsing forms of MS.

Traditionally, B-cell treatments, which bind to and deplete B-cells associated with disease activity in MS, have predominantly been available in hospitals or infusion treatment centers, which can add costs to the healthcare system and present a lifestyle burden for some patients7,8. Kesimpta provides patients the flexibility of self-administering via once-monthly subcutaneous dosing requiring no premedication, eliminating the need to travel to an infusion center. The positive results from the APLIOS studyan open-label Phase II study to determine the bioequivalence of subcutaneous delivery of Kesimpta via a prefilled syringe and a Sensoready pen in patients with RMSand the ASCLEPIOS studies show Kesimpta to be a highly effective B-cell therapy that can be easily self-administered at home1,3.

At Novartis, we challenge treatment paradigms and strive to offer the best treatment choice for patients, said Marie-France Tschudin, President, Novartis Pharmaceuticals. When treating patients with RMS, Kesimpta is a meaningful treatment option that delivers both high efficacy and safety with the ability for patients to have more freedom in managing their disease. The development of Kesimpta is a great example of our commitment, knowledge and understanding of multiple sclerosis, which enabled us to identify a targeted treatment that can significantly improve patient outcomes and experience.

Ofatumumab was first approved by the FDA in 2009 for the treatment of chronic lymphocytic leukemia (CLL) as an intravenous infusion with a high dose, administered by a healthcare provider. Ofatumumab was then investigated in an entirely new development program in RMS, as B-cells are known to play a critical role in the development of autoimmune diseases, such as MS7. The clinical development program for ofatumumab in RMS took 10 years and has involved more than 2,300 patients around the world as part of rigorous studies that were reflective of the broad patient population. Kesimpta was found to work through a distinct mode of action, and the treatment regimen (dosing)which was specifically designed for RMSplays a critical role in the outcome9. This is a different dosing regimen and route of administration than was previously approved for the CLL indication.

The approval of Kesimpta is based on results from the Phase III ASCLEPIOS I and II studies, in which Kesimpta demonstrated superiority versus teriflunomide in significantly reducing the annualized relapse rate (ARR, primary endpoint), 3-month confirmed disability progression (CDP), and the number of gadolinium-enhancing (Gd+) T1 and new or enlarging T2 lesions1. Results from these two studies were recently published in the August 6, 2020 issue of The New England Journal of Medicine.

Kesimpta is expected to be available in the United States in early September.* Additional regulatory filings are currently underway across the world, and regulatory approval for Kesimpta in Europe is expected by Q2 2021.

*Time of availability may vary as healthcare providers integrate Kesimpta into their practices.

About ASCLEPIOS I and II studiesThe ASCLEPIOS I and II studies are twin, identical design, flexible duration (up to 30 months), double-blind, randomized, multi-center Phase III studies evaluating the safety and efficacy of Kesimpta 20 mg monthly subcutaneous injections versus teriflunomide 14 mg oral tablets taken once daily in adults with RMS. The ASCLEPIOS I and II studies enrolled 1,882 patients with MS, between the ages of 18 and 55 years, with an Expanded Disability Status Scale (EDSS) score between 0 and 5.51. The studies were conducted in over 350 sites in 37 countries10. Kesimpta demonstrated a significant reduction in ARR by 51% (0.11 vs 0.22) and 59% (0.10 vs 0.25) compared with teriflunomide (P<.001 in both studies) in ASCLEPIOS I and II, respectively (primary endpoint). Kesimpta also showed a relative risk reduction of 34.4% (P=.002) in 3-month CDP compared with teriflunomide in pre-specified meta-analysis, as defined in ASCLEPIOS1.

Kesimpta showed significant reduction of both Gd+ T1 lesions and new or enlarging T2 lesions. It significantly reduced the mean number of both Gd+ T1 lesions (98% and 94% relative reduction in ASCLEPIOS I and II, respectively, both P<.001) and new or enlarging T2 lesions (82% and 85% relative reduction in ASCLEPIOS I and II, respectively, both P<.001) vs teriflunomide1.

Kesimpta had a similar safety profile to teriflunomide, with the frequency of serious infections and malignancies also being similar across both treatment groups1. Upper respiratory tract infection, headache, injection-related reactions, and local injection site reactions were the most commonly observed adverse reactions with Kesimpta (incidence greater than 10%)1.

A separate post hoc analysis demonstrated Kesimpta may halt new disease activityin RMS patients. It showed the odds of achieving no evidence of disease activity (NEDA-3; no relapses, no MRI lesions, and no disability worsening combined) with ofatumumab versus teriflunomide were >3-fold higher at Months 012 (47.0% vs 24.5% of patients; P<.001) and >8-fold higher at Months 1224 (87.8% vs 48.2% of patients; P<.001)2.

Overall Kesimpta, an antibody targeting CD20 positive B-cells, delivered superior efficacy and demonstrated a safety profile with infection rates similar to teriflunomide1.

About APLIOS studyThe APLIOS study is a 12-week, open-label, Phase II bioequivalence study to determine the onset of B-cell depletion with Kesimpta subcutaneous monthly injections and the bioequivalence of subcutaneous administration of Kesimpta via a prefilled syringeas used in ASCLEPIOS I and IIand a Sensoready pen in patients with RMS. Patients were randomized according to injection device and site including the abdomen and the thigh. B-cell depletion was measured nine times over 12 weeks and Gd+ lesion counts were assessed at baseline and at Weeks 4, 8 and 12. Regardless of injection device or site, Kesimpta 20 mg subcutaneous monthly injections resulted in rapid, close to complete and sustained B-cell depletion; the proportion of patients with B-cell concentrations of <10 cells/L was >65% after the first injection by Day 7, 94% by Week 4, and sustained >95% at all following injections. Kesimpta treatment reduced the mean number of Gd+ lesions from baseline (1.5) to 0.8, 0.3 and 0.1 by Weeks 4, 8 and 12, respectively; the proportion of patients free from Gd+ lesions at the corresponding time points were 66.5%, 86.7% and 94.1%, respectively3.

About Kesimpta (ofatumumab, formerly OMB157)Kesimpta is a targeted, precisely dosed and delivered B-cell therapy that provides the flexibility of self-administration for adults with RMS. It is an anti-CD20 monoclonal antibody (mAb) self-administered by a once-monthly injection, delivered subcutaneously1,3. Initial loading doses of Kesimpta are given at Weeks 0, 1 and 2, with the first injection performed under the guidance of a healthcare professional. As shown in preclinical studies, Kesimpta is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion9. The selective mechanism of action and subcutaneous administration of Kesimpta allows precise delivery to the lymph nodes, where B-cell depletion in MS is needed, and preclinical studies have shown that it may preserve the B-cells in the spleen11. Once-monthly dosing of Kesimpta also allows faster repletion of B-cells and offers more flexibility12. Ofatumumab was originally developed by Genmab and licensed to GlaxoSmithKline. Novartis obtained rights for ofatumumab from GlaxoSmithKline in all indications, including RMS, in December 201513.

About Multiple Sclerosis Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by myelin destruction and axonal damage in the brain, optic nerves and spinal cord14. MS, which affects approximately 2.3 million people worldwide15, can be characterized into four main types of MS: clinically isolated syndrome (CIS), relapsing remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS)16. The various forms of MS can be distinguished based on whether a patient experiences relapses (clearly defined acute inflammatory attacks of worsening neurological function), and/or whether they experience progression of neurologic damage and disability from the onset of the disease14.

Novartis in NeuroscienceNovartis has a strong ongoing commitment to neuroscience and to bringing innovative treatments to patients suffering from neurological conditions where there is a high unmet need. We are committed to supporting patients and physicians in multiple disease areas, including MS, migraine, Alzheimer's disease, Parkinson's disease, epilepsy and attention deficit hyperactivity disorder, and have a promising pipeline in MS, Alzheimer's disease, spinal muscular atrophy and specialty neurology.

DisclaimerThis press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as potential, can, will, may, could, expected, committed, commitment, promising, pipeline, addressing, underway, to include, or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for Kesimpta, or regarding the timing of availability of Kesimpta in the United States, or regarding regulatory approval of Kesimpta in Europe, or regarding potential future revenues from Kesimpta. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that Kesimpta will be submitted or approved for sale or for any additional indications or labeling in Europe or in any other markets, or at any particular time. Neither can there be any guarantee that Kesimpta will be available in early September, or in any other time frame, in the United States. Nor can there be any guarantee that Kesimpta will be commercially successful in the future. In particular, our expectations regarding Kesimpta could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally, including European regulatory authorities not approving Kesimpta in the expected time frame, or at all; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AGs current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

Dr. Hausers statements reflect his professional opinion and not necessarily the views of The Regents of the University of California. Nothing in his statements shall be construed to imply any support or endorsement of Novartis, or any of its products, by The Regents of the University of California.

About NovartisNovartis is reimagining medicine to improve and extend peoples lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the worlds top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 109,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com.

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References1. Kesimpta Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corp; August 2020.2. Hauser S, Bar-Or A, Cohen J, et al. Ofatumumab versus teriflunomide in relapsing multiple sclerosis: analysis of no evidence of disease activity (NEDA-3) from ASCLEPIOS I and II trials. Eur J Neurol. 2020;27(S1).3. Bar-Or A, Fox E, Goodyear A, et al. Onset of B-cell depletion with subcutaneous administration of ofatumumab in relapsing multiple sclerosis: results from the APLIOS bioequivalence study. Poster presentation at: ACTRIMS; February 2020; West Palm Beach, FL.4. Winkelmann A, Loebermann M, Reisinger EC, Hartung HP, Zettl UK. Disease-modifying therapies and infectious risks in multiple sclerosis. Nat Rev Neurol. 2016;(4):217-33.5. The Multiple Sclerosis Coalition. The use of disease-modifying therapies in multiple sclerosis: principles and current evidence. Accessed August 12, 2020. http://ms-coalition.org/the-use-of-disease-modifying-therapies-in-multiple-sclerosis-updated/6. Cree BA, Mares J, Hartung HP. Current therapeutic landscape in multiple sclerosis: an evolving treatment paradigm. Curr Opin Neurol. 2019;32(3):365-377.7. Lehmann-Horn K, Kronsbein HC, Weber MS. Targeting B cells in the treatment of multiple sclerosis: recent advances and remaining challenges. Ther Adv Neurol Disord. 2013;6(3):161-173.8. Dieguez G, Engel T, Jacobson N. Site of service and cost dispersion of infused drugs. Accessed August 12, 2020. https://www.milliman.com/insight/2019/Site-of-Service-and-Cost-Dispersion-of-Infused-Drugs/9. Smith P, Kakarieka A, Wallstroem E. Ofatumumab is a fully human anti-CD20 antibody achieving potent B-cell depletion through binding a distinct epitope. Poster presentation at: ECTRIMS; September 2016; London, UK.10. Kappos L, Bar-Or A, Cohen J, et al. Ofatumumab versus teriflunomide in relapsing multiple sclerosis: baseline characteristics of two pivotal phase 3 trials (ASCLEPIOS I and ASCLEPIOS II). Poster presentation at: ECTRIMS; October 2018; Berlin, Germany.11. Smith P, Huck C, Wegert V, et al. Low-dose, subcutaneous anti-CD20 therapy effectively depletes B-cells and ameliorates CNS autoimmunity. Poster presentation at: ECTRIMS; September 2016; London, UK.12. Savelieva M, Kahn J, Bagger M, et al. Comparison of the B-cell recovery time following discontinuation of anti-CD20 therapies. ePoster presentation at: ECTRIMS; October 2017; Paris, FR.13. Genmab Press Release: Genmab announces completion of agreement to transfer remaining ofatumumab rights. December 21, 2015. Accessed August 12, 2020. https://ir.genmab.com/static-files/9d491b72-bb0b-4e46-a792-dee6c29aaf7d14. Guthrie E. Multiple sclerosis: a primer and update. Adv Studies Pharm. 2007;4(11):313-317.15. Multiple Sclerosis International Federation. Atlas of MS 2013-Mapping Multiple Sclerosis Around the World. Accessed August 12, 2020. http://www.msif.org/wp-content/uploads/2014/09/Atlas-of-MS.pdf 16. National MS Society. Types of MS. Accessed August 12, 2020. https://www.nationalmssociety.org/What-is-MS/Types-of-MS

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FDA approves Novartis Kesimpta (ofatumumab), the first and only self-administered, targeted B-cell therapy for patients with relapsing multiple...

In an interview with Medical News Today, James Hindley, Ph.D., from Indoor Biotechnologies explains how his company is developing a new T cell test during the COVID-19 pandemic. He also reveals why this test is a much-needed tool for those designing new vaccines and studying immune responses to the new coronavirus.

Since the COVID-19 pandemic began, scientists across disciplines and geographical locations have collaborated in unprecedented ways.

The speed at which diagnostic tests went from conception to reality was astounding, as were the global efforts to test new and repurposed drugs to find treatments for those with the disease.

However, effective treatments are only tentatively emerging. Diagnostic testing capabilities have been slow to ramp up to the scales needed to keep the pandemic at bay.

Many questions remain about how the virus causes catastrophic deterioration in some but leaves many others relatively unscathed.

Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.

Undeterred, investigators continue to research and develop new arsenals in this global fight.

Medical News Today spoke to one such scientist, who recently began a new project with a grant from the British governments Innovate UK fund.

James Hindley, Ph.D., is the Executive Director at Indoor Biotechnologies in Cardiff in Wales, and the work is underway in collaboration with Martin Scurr, Ph.D., a research associate at Cardiff Universitys School of Medicine.

Working with the team at Indoor Biotechnologies, Dr. Hindley and Dr. Scurr are developing a new type of test that can show if someone has developed specific T cells to SARS-CoV-2.

T cells are a type of white blood cell. They play a key role in how our bodies fight off viral pathogens, such as SARS-CoV-2, the new coronavirus.

MNT: Why is there a need to develop a new T cell test?

Dr. James Hindley: The current focus for testing immunity to the SARS-CoV-2 virus is based on the assessment of antibodies.

These are an undoubtedly important part of our memory immune response to viruses. However, another critical component of our immune response to viruses is the T cell. These also provide memory immune responses and may even be more sensitive than antibodies.

The challenge with T cells is that, unlike antibodies, measuring them is not simple.

As such, there is a need for a simple T cell test, that could enable testing for virus-specific T cells to be done routinely.

MNT: What will the test results show?

Dr. Hindley: The test we have developed can provide quantitative results measuring the magnitude of an individuals T cell response to the SARS-CoV-2 virus.

We can also run in parallel the same test for other human coronaviruses and viruses, such as influenza. This allows us to establish a persons immune status. Like antibodies, whether a positive T cell test is protective against future infection remains to be determined.

MNT: Who will benefit from your test, and who can administer it?

Dr. Hindley: At first, we believe the primary use of this test will be for vaccine development, to determine whether a T cell response to the vaccine has been generated and whether that is adequate to be protective from infection.

Such testing would be done in laboratories, alongside other tests needed for the vaccine trial.

We also believe this test will enable public health bodies to perform much wider screenings of the population. Again, this would be carried out by laboratories in conjunction with antibody testing to determine what constitutes protective immunity.

Once this is proven, the assessment could then be made available to the wider public, but it is likely to remain as a test performed in a laboratory.

MNT: Are there other tests available, and how is yours different from these?

Dr. Hindley: At present, there are no tests for measuring T cells to SARS-CoV-2 in a high throughput manner.

Any T cell testing for SARS-CoV-2 has been performed as part of a research study in a handful of specialist laboratories. These laboratories use specialist techniques, most commonly techniques called flow cytometry or ELISpot, which require highly trained staff and relatively expensive equipment.

The main drawbacks of these techniques are that they are relatively long, laborious, and therefore do not have high throughput. They are also difficult to standardize.

Where we were innovative was looking at the minimum requirements to perform this test, to get the necessary data to answer the question of whether a person has specific T cell responses.

By providing just these elements without the added complexity, we made this test much easier to perform in almost any lab, using routine laboratory equipment. Our test also uses whole blood, rather than a population of precursor cells, which require an additional step to purify.

The test uses specific parts of the virus to stimulate virus-specific memory T cells within the blood to release cytokines. Were able to detect these cytokines within hours of them after production.

MNT: Given that we are currently in a pandemic, how has the way you develop your technology changed compared to how you would normally design a new test?

Dr. Hindley: The main change has been the speed at which we have operated, both internally and externally.

The initial funding from Innovate UK was turned around within 30 days. We were given fast-track approval for our research and ethics committee application. In addition, participants have been keen to make themselves available for testing.

It feels like everyone is coming together and working around the clock to try to tackle this pandemic.

MNT: How did your collaboration come about?

Dr. Hindley: Martin and I did our Ph.Ds. at the same institute and are longstanding colleagues and friends.

The collaboration on this project came about as we were in close contact throughout the start of the pandemic, primarily watching from afar and debating the science.

Then when we heard about the call for funding from Innovate UK to support the development of innovations for tackling COVID-19, we put in an application as we felt like we had a great idea which could genuinely help in the fight against this virus.

For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.

Continue reading here:
COVID-19: How a new blood test could help speed up vaccine development and population screening - Medical News Today

Large processes sometimes occur on a small scale. "Microfluidics is the world in which entire processes conducted in the laboratory are miniaturized into tiny containers," explains Prof. Doron Gerber. In chemistry, biology and other fields, the processes take place in a liquid environment, even when working with miniature dimensions, hence the name 'microfluidics.'

'Laboratory-on-a-chip,' that is based on microfluidics, enables us to simultaneously conduct multiple and complex sets of experiments that generate a high data output such as a survey of biochemical, physical and cell data, with a tremendous saving in the number of samples required and the duration of the experiment.

Prof. Doron Gerber is a researcher in the Nanotechnology Center and Faculty of Life Sciences at Bar Ilan University. "My background is in biology," he says. "After a doctorate that examined membranal proteins, I decided to do something of a more technological nature. I completed a post doctorate with Prof. Stephen Quake at Stanford a researcher who introduced me to the whole field of controlled microfluidics. Prof. Quake invented a new type of microfluidics that enables us to conduct extremely complex experiments and to develop applications in the fields of biology, chemistry, and physics by using flexible switches that enable complete control of whatever happens inside the chip. In other words, the technology allows smart management of small nano-liter quantities of fluids.

"How does it all work? Let's say that we want to conduct 1,000 simultaneous experiments. First, we need a sample of the substance we are studying such as, a drop of blood. In regular experiments, we only have a limited number of available samples, either because they are taken from a single person or because they are very expensive.

"Microfluidics allows us to perform complex procedures with tiny amounts of samples. Let's imagine that I had an endless quantity of blood to examine: I would take 1,000 test tubes and attempt to perform one experiment using different substances on a blood sample in each one according to the parameter I wanted to test.

"Here, we miniaturize the experiment set so that we have 64 micro-cavities instead of test tubes. Each of these cavities contains only one-thousandth of a drop of the patient's blood. Each cavity is one quarter of a square millimeter and is 20 microns high, so its volume is only a few nano-liters (1 nano-liter is one millionth of a liter). The passages between the micro-cavities are canals, each up to a hairbreadth wide, through which the substances required for the different experiments move. Multiply this set by 64 levels and you can conduct thousands of experiments at the same time.

"To make it work, we need each experiment to remain separate from the others, so we created a 'door' that in addition to separation also allows us to insert and extract things. This door is an elastic switch that opens and closes according to instructions given from a computer software.

"In other words, our microfluidic chips are set of extremely small cavities and a system of fully controlled switches ('doors') capable of timed insertion and extraction of substances from the cavities. An experiment set like this can be used in a wide range of scientific experiments such as searching for substances in the blood like antibodies, pieces of DNA or RNA from a viral source, indicators of cancer etc. A small volume of a patient's blood can be used as a sample, inserted into the chip so that each of the chip's many cavities contains a small drop of blood and can 'host' a test to locate the substance under examination, enable its quantification, or a qualitative analysis that indicates its presence in the blood.

"In other experiments, such as those that check the connection between proteins of different viruses and human proteins, we can start from the level of the genetic material of a person or a virus, translate it into proteins that are given fluorescent markers (fluorophores) in the chip's cavities, and evaluate the degree and strength of the connection created between these proteins. Information such as this is extremely valuable in studying viruses' operating mechanisms and the way they influence human cells. Finding a strong connection between a viral protein and a human protein hints to the involvement of these proteins in the way the virus infects or spreads and can therefore constitute a target site for the development of a treatment for that virus.

"In addition to working with different molecules, the microfluidic platform also enables us to work with whole cells.

"In the field of cancer research, there is a good correlation between the results of the laboratory experiment and clinical results. Nevertheless, the main problem is that a sample taken from a cancer patient contains many cancer cells and there is no way to cultivate them in such a way as to be able to conduct dozens of experiments and analyze their influence on a range of possible treatments. In an attempt to overcome this obstacle, scientists are trying to grow the tumor cells in the lab and increase their number and only then expose them to different treatments, but this is a race against time.

"We have developed a microfluidic chip for culturing the cells. Each of the chip's cavities can accommodate a tiny quantity of cancer cells taken from a specific patient and allows us to expose each group of cells to a different pharmaceutical treatment and check their reaction to it. This method enables us to know which treatment the cancer cells are resistant or sensitive to and how they respond, all within just a couple of days.

"Although there are currently many drugs for treating cancer, it's not clear how each patient will respond to each of them. A specific drug may cause harsh side effects and be ineffective in treating the disease so the window of opportunity for treating these patients is extremely limited. The results of an experiment using our chip can help direct the patient's physician to choose the most efficient treatment for him, thereby saving precious time and unnecessary suffering.

"A year ago, we published an initial paper in which we proved the theory and presented the system's capabilities. We have now begun checking patient samples. The paper gained considerable interest, and many have expressed a wish to examine samples using our system.

"We recently began collaborating with Dr. Amir Onn, Head of the Institute of Pulmonary Oncology at the Sheba Medical Center and Dr. Limor Broday from Tel Aviv University. The time limit with lung cancer is especially short. From the moment the patient stops responding to treatment, a doctor needs to receive the relevant knowledge and make a very quick informed decision regarding alternative treatment. In our joint study, we attempt to assess whether our method can facilitate a swift and accurate decision, thereby enhancing the results of the treatment administered to the patient.

"There is a tremendous need in this field, and we are attempting to get financing from scientific grants that will enable us to survey about 300 patients over the next two years. This will, in turn, allow us to characterize the system in relation to a set of lung cancer medications while simultaneously upgrading the system that checks the vitality and mortality data following exposure to the medication. In the future, we hope to add a further capability to the system that will facilitate the measurement of metabolic indices which report on processes within the cells such as glucose and energy levels, and that provide more in-depth information.

"The device's complexity means that the need for large-scale investment is a fundamental issue in the chips' production processes. Our dream is to enable biologists to take an idea and bring it to engineering implementation: lab production of a chip. This for me is the essence of Bio-convergence a biologist using sophisticated engineering to create innovative solutions.

"We built a factory at Bar Ilan University for producing microfluidic chips, not only for my laboratory but also for additional labs at Bar Ilan and other institutions as well as for Israeli industry, but we belong to academia and it's only a small factory with limited human and financial resources. As of now, our largest challenge is to enable industry to utilize the potential of the infrastructure we have constructed, he said.

Prof. Gerber predicts a rosy future for the tiny chips: "It's happening all around the world microfluidics is entering the world of diagnostics and the field of developing tools for scanning medications and substance synthesis e.g., therapeutic antibodies or antibodies for genetic engineering of viruses etc.

"The industry needs microfluidic chips to produce therapeutic antibodies and to market them as drugs and increasingly more microfluidic tools are appearing in manufacturing or development processes. As of now, this kind of research only exists on a small scale in Israel, primarily in academia, with large-scale microfluidic centers needed to integrate the technology into the industry. If, for instance, we assume that a startup company receiving a limited initial sum of money wants to use a microfluidic tool, its chances of success are slight. Among the reasons for this is the lack of appropriate infrastructures production of a simple microfluidic chip requires a manufacturing plant with clean rooms, equipment for creating molds by lithographic processes, equipment for coating molds, and equipment for producing the chips.

"Today, when it is obvious to everyone that there is a need to connect biology and high-tech, it is also clear that most of the major tools for doing so actually exist in academia far more than in industry. On the other hand, academia lacks the large-scale infrastructures required to transform technology into an off-the-shelf product like production of a chip prototype. Since entering academia, I have established, and am still establishing, a microfluidic chip center capable of producing different kinds of chips and providing support to new researchers seeking to make use of microfluidic technology, all subject to the limitations of the existing support in academia.

"There is no doubt that large-scale investment and significant financial incentives directed at the development of basic infrastructures are required for the field of microfluidics to transcend the walls of academia and penetrate industrial realms. In contrast to biology for example, where you can buy a robot to perform large quantity tasks, microfluidics is characterized by a scarcity of companies that develop these tools for others. Investment in this infrastructure will enable companies to make use of off-the-shelf products and to integrate these innovative technologies into their applications. Young industry must also be connected to academic capabilities.

"Many companies who come to our nanotechnology center for example, use our equipment and at the same time, receive good counseling. But this happens at an academic pace. We must invest a little more in this infrastructure so that it serves industry better, for example, in the establishment of a consortium which we aspire to be a member of."

Dr. Itai Kela, Scientific Director of the Bio-Convergence Program:

"The integration of microfluidics used for discovering new medicines and 'lab-on-a-chip' systems creates an amazing technology that enables to dramatically reduce the use of lab animals when developing drugs and constitutes an engineering technological platform for the scanning and more rapid and efficient detection of new medicines and treatments."

The Sensors that Discover Why Medications Fail

When discussing Bio-convergence and the combination of industry and academia, it is important to learn about the work of Prof. Yaakov "Koby" Nahmias. Prof. Nahmias, Founding Director of the Bioengineering Center at the Hebrew University in Jerusalem, is a serial entrepreneur and Chief Scientist of the Tissue Dynamics corporation which he founded a year ago.

"Bio-convergence the structured combination of engineering biology and medicine is a very important part of projects' technological maturity and enables amazing breakthroughs," he says. "In practice, one of the main reasons behind the establishment of the Bioengineering Center at the Hebrew University was the desire to provide an academic response to the growing need for engineers who understand biology and vice versa."

As an example of the importance of Bio-convergence, Prof. Nahmias relates to the coronavirus: "When the 'Hepatitis C' virus was discovered in the year 2000, it took 3-4 years to sequence it and then an entire year to grow it. The first medication arrived only several years later. In other words, it took about a decade to develop molecules capable of contending with 'Hepatitis C'.

"In contrast, the new coronavirus was only discovered in November and was more or less sequenced already in December. Its first tissue cultures were ready in January-February with the first molecules being introduced to clinical research around March. What took years with 'Hepatitis C' is being done in just weeks and a few short months with Covid-19. This is much more than an exponential increase it's a quantum leap.

"Today's world moves extremely fast and investors need to take into account that the pharma industry is going to reverse itself. The 1970s and 1980s were characterized by a lot of mediocre pharma companies, most of which were swallowed up by a small number of pharma giants that are the only ones with the massive resources necessary to bring a new drug to the market. The next technological revolution will enable an entire community of small pharma companies to compete with the giants.

"I am a member of the Innovation Authority's Bio-convergence Committee that will lead a dramatic breakthrough in Israel's technological capabilities. The Authority helps the academic world penetrate industry, receive necessary resources, and transform theoretical solutions into practical applications. If until 15 years ago the world of academia was extremely theoretical and did not view the connection with industry as something positive, I believe that this view has changed over the last decade. Today, both the universities and their academic staff are very interested in industry and are working closely with the Authority. The attitude has changed even more in recent years during which young faculty members are themselves beginning to lead startup companies to the market and I hope that this trend will continue, he said.

Tissue Dynamics operates in the 'organ-on-a-chip' field and seeks to change the world of pharma development.

"Drug development is a long and high-risk process," Prof. Nahmias explains. "2.6 billion dollars and 10-12 years are required to bring a new drug to the market. For each molecule that reaches the medical market, there are 90 others that fail despite the huge resources invested in them. Every molecule that fails at the animal testing stage or in clinical trials costs hundreds of millions of dollars. Drugs sometimes fail even after FDA approval, release to the market, or administration to patients.

"This is the reason that although there are hundreds of companies developing pharmaceuticals in Israel, none of them has the resources to reach the market. These companies will eventually be sold to a pharma giant which will then conduct the final clinical trials. This reality limits Israel's ability to compete with other countries.

"One of the main reasons that drugs fail is that we develop them on animals. We have drugs that work well in mice but not in humans. Another problem is that we don't understand precisely why a drug fails clinical trials. It's a kind of black box that means we can't just change the molecule and move forward we have to start again from the beginning. That's why pharmaceutical development is such a Sisyphean, costly and long process.

"The 'organ-on-a-chip' story began more than a decade ago when an entrepreneur approached my lab at Harvard to ask for help with developing the technology. The idea is to take human cells with human genetics and metabolism and place them on a microfluidic chip that simulates human physiology in order to grow tissues of different organs. The microfluidic chip is made of plastic and is about the size of a 5-shekel coin. Instead of conducting an experiment on a rat or a mouse, we use a microfluidic chip containing tiny tissues of human organs.

"I am very interested in this field and I developed the first 'organ-on-a-chip' technology that was commercialized for an American company called HuREL. Although the technology met the need for human trials, it didn't solve the second problem attaining a clear understanding of why a drug doesn't work.

"When I returned to Israel to set up the bioengineering center, I focused on the attempt to solve both problems simultaneously. For five years, we developed a technology that enables us to take human cells, use them to create human liver, heart, brain and kidney tissues, and to insert into them sensors that allow us to measure the tissues' activity in real time. This in turn gives us the ability to discover what happens to human tissue when we give it a drug or during a disease.

"The sensors operate exactly as they do in a motor vehicle: if the vehicle shuts down, the oil warning light flashes and we understand the problem. When I administer a drug to healthy tissue that suddenly stops working, I know precisely where that molecule has hit. If I insert a molecule into a heart in which I identify a disease and it restores the regular heartbeat, the sensors show me why it works.

"This technology enables us to completely alter the world of pharmaceuticals. It can reduce development costs up to 80% which means that it will be possible to develop a drug from scratch and bring it to the market for the cost of a few hundred million dollars. This has tremendous significance for the Israeli economy. Hundreds of Israeli pharma companies may not be sold but rather, reach the market by themselves."

The Road to Decentralizing Drug Development

Tissue Dynamics was founded two years ago. As Prof. Nahmias explains: "we started out as a small company, without any external funding. We gave giant companies like L'Oral, Merck, and Teva access to our technology so that they would understand its potential. Several months ago, just before the Corona crisis, we embarked on a funding round for initial investments.

"We are currently at the stage of slowly moving out of the university. We have independently developed new molecules for treating arthritis and cancer and are now taking our platform in the direction of a new model of drug development. This is Tissue Dynamics' second and more mature corporate stage.

"Our overall vision is of a decentralized drug development structure: a cloud-based smart learning program that has access to several Tissue Dynamics systems distributed between leading labs around the world. The primary platform is situated at our company where we are developing new biological and molecular models but also forging contacts with leading labs worldwide and assimilating our technologies there. These contacts allow us to create biological and chemical data and information that are not just ours, and to include information from other groups worldwide. Our first collaboration in the US is with ATCC (American Type Culture Collection), the world's largest cell and tissue database. ATCC has about 4,500 human tissues from healthy and sick people and access to such information allows us a much deeper understanding of the different mechanisms.

"Six months ago, we developed a new model of the human kidney that enables us to observe a drug's activity and toxicity in the kidney. One of the drugs we examined is called cyclosporine and is given to patients who received organ transplants or who suffer from arthritis. Cyclosporine generates global sales revenues of approximately 4 billion dollars a year despite the known fact that it causes kidney damage.

"When we inserted the drug into a kidney, the sensors were activated and provided us with an energy map of how the drug behaves in a human kidney. Strangely, it turns out that it activates the same mechanism as that in a fatty liver. Nobody knew about this mechanism previously and it was impossible to see without our sensors. This breakthrough meant that we could perform a quick reformulation of the drug and reduce its toxicity. We believe that this constitutes a revolutionary breakthrough in drug development."

The article was written in collaboration with the Israel Innovation Authority, responsible for the countrys innovation policy. Its role is to nurture and develop Israeli innovation resources, while creating and strengthening the infrastructure and framework needed to support the entire knowledge industry.

See more here:
A quantum leap In the drug development world - CTech

Mutations in either protein CLN6 or CLN8 result in two forms of Batten disease with remarkably similar clinical features. It turns out, as recently shown by the laboratory of Dr. Marco Sardiello, that both proteins work together to equip lysosomes, the waste-disposal hubs of the cell, of the much needed enzymes that process cellular waste.

Batten disease is a family of 13 rare, genetically distinct conditions. Collectively, they are the most prevalent cause of neurodegenerative disease in children, affecting 1 in 12,500 live births in the U.S. One of the Batten disease genes is CLN6. How mutations in this gene lead to the disease has been a mystery, but a study led by researchers at Baylor College of Medicine and published in the Journal of Clinical Investigation reveals how defective CLN6 can result in Batten disease.

People with Batten disease have problems with their cells ability to clear cellular waste, which then accumulates to toxic levels, said first author Dr. Lakshya Bajaj, who was working on this project while a doctorate student in the Sardiello lab at Baylor. Bajaj is currently a post-doctoral associate at Harvard Medical School.

In cells, lysosomes process cellular waste. They are sacs containing enzymes, a type of proteins that break down waste products into its constituent components that the cell can recycle or discard. In Batten disease caused by mutations in CLN6, the lysosomes do not process waste effectively for unknown reasons. This results in waste accumulation. Batten disease is a type of lysosomal storage disorder. Although all types of cells can be affected by defects in lysosomal waste management, brain cells, neurons, are particularly susceptible.

Waste accumulation in neurons perturbs many cellular processes and eventually results in cell death. This leads to the progressive degeneration of motor, physical and intellectual abilities observed in Batten disease patients, Bajaj said.

The connection of CLN6 with Batten disease was a bit of a mystery. This protein is not found in lysosomes, but in the endoplasmic reticulum, a structure inside cells where proteins, including lysosomal enzymes, are made. The endoplasmic reticulum is separate from the lysosomes. So, how do defects in a protein located outside of the lysosomes interfere with lysosomal function?

The Sardiello lab had previously solved a similar mystery involving CLN8, another protein located in the endoplasmic reticulum and whose mutations also cause a type of Batten disease.

We showed that CNL8 assists on the exit of lysosomal enzymes from the endoplasmic reticulum en route to the lysosomes. When CLN8 is defective, the transport of enzymes from their place of synthesis to the final destination is deficient and the lysosomes end up having fewer enzymes to work with, said Sardiello, associate professor of molecular and human genetics at Baylor and corresponding author of this work.

The clinical manifestations of Batten disease caused by CLN8 mutations and those of Batten disease due to defective CLN6 are remarkably similar. This and other evidence led the researchers to suspect that CLN6 and CLN8 might be working together.

Their investigations revealed that CLN6 and CLN8 do interact with each other forming a molecular complex that collects lysosomal enzymes at the endoplasmic reticulum and mediates their trafficking towards the lysosomes.

We propose that CLN8 and CLN6 together herd the enzymes into a hub, a sort of bus stop. Then, CLN8 escorts the enzymes on the bus en route to the lysosomes, while CLN6 remains at the bus stop. CLN8 returns to the bus stop after delivering the enzymes, and they repeat the process, Bajaj said. When CLN6 is defective, the enzymes are not effectively herded into the bus stop and fewer are transported to the lysosomes.

The researchers are interested in finding whether other factors are involved in transporting enzymes to the lysosomes. For instance, whether there are other bus conductors or herders of lysosomal enzymes involved that, if defective, may also contribute to Batten disease.

Other contributors to this work include Jaiprakash Sharma, Alberto di Ronza, Pengcheng Zhang, Aiden Eblimit, Rituraj Pal, Dany Roman, John R. Collette, Clarissa Booth, Kevin T. Chang, Richard N. Sifers, Sung Y. Jung, Jill M. Weimer, Rui Chen and Randy W. Schekman. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine; Texas Childrens Hospital; University of California, Berkeley; Sanford Research, Sioux Falls, South Dakota; and Sanford School of Medicine at the University of South Dakota.

This work was supported by NIH grants NS079618 and GM127492 and grants from the Gwenyth Gray Foundation, Beyond Batten Disease Foundation and NCL-Stiftung. This project was supported in part by IDDRC grant number 1U54 HD083092 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Integrated Microscopy Core and the Proteomics Core at Baylor College of Medicine with funding from NIH (DK56338, and CA125123), CPRIT (RP150578, RP170719), the Dan L Duncan Comprehensive Cancer Center and the John S. Dunn Gulf Coast Consortium for Chemical Genomics.

By Ana Mara Rodrguez, Ph.D.

Read more:
Image of the Month: Locating molecular players in Batten disease - Baylor College of Medicine News

This report is 80% complete and can be delivered within three working days post order confirmation and will include the latest impact analysis of Covid-19 in 2020 and forecast. Global Regenerative Medicine Market By Therapy (Cell-Based Immunotherapy & Cell Therapy, Gene Therapy, Others), By Application (Musculoskeletal Disorders, Wound Care, Others), By Material (Synthetic Material, Biologically Derived Material, Others), By Cell (Autologous, Allogenic), By Product (Biologic, Cell -based Medical Devices, Others), By Technique (Microfracture, Mosaicplasty), By Distribution Channel (Hospitals, Clinics , Others), By Region, Forecast & Opportunities, 2025

New York, June 30, 2020 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Global Regenerative Medicine Market By Therapy, By Application, By Material, By Cell, By Product, By Technique, By Distribution Channel, By Region, Forecast & Opportunities, 2025" - https://www.reportlinker.com/p05916746/?utm_source=GNW

Global regenerative medicine market is expected to register a double digit CAGR through 2025 owing to their increasing use in repair, replacement or regeneration of cells, tissues and organs. Additionally, high prevalence of chronic & genetic dieses, emergence of stem cell technology and growing aging populations are some of the key factors driving the regenerative medicine market.

Regenerative medicines deal with process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function.They are also being used to create solutions for organs that become permanently damaged.

These medicines are also used in treatment of some uncurable dieses like arthritis and diabetes. Increasing number of cancer patients, neurodegenerative, orthopedic, and other aging-associated disorders is creating a significant demand for regenerative medicine market globally. Various countries like United States, China and Japan are investing in stem cell research, which indicates a bright future for regenerative medicine manufacturers.

The global regenerative medicine market also faces some restraints like high treatment costs, stringent government regulations and operative inefficiency. High investment required for developing the medicine might also limit the market growth.

The market is segmented based on therapy, application, material, cell, product, technique, distribution channel and region.The application segment comprises of musculoskeletal disorders, wound care, oncology, neurology, ocular disorders, diabetes, cardiology and others.

Out of them, the musculoskeletal segment is expected to dominate the market during the forecast years owing to growing use of regenerative medicines for treating musculoskeletal disorders and increasing number of orthopedic diseases.Based on material, the regenerative medicine market is segmented into synthetic material, biologically derived material, genetically engineered material and pharmaceutical.

The biologically derived material dominated the regenerative medicine market in 2019 and is expected to further hold its position in the coming years due to its unique properties. This type of material promotes cellular interactions, increases proliferation and controls the manipulation of cellular behavior. Major players operating in the global regenerative medicine market include Novartis AG, Vericel, Integra Lifesciences, Mimedx Group, Stryker, Wright Medical, Roche, Bristol-Myers Squibb, Allergan, Corline Biomedical, Cook Biotech, Pfizer, Baxter, Boehringer Ingelheim, Caladrius Biosciences, Takara Bio, Medtronic, Osiris Therapeutics, Kite Pharma, Organogenesis and others. Due to growing demand from Asia-Pacific region, the manufacturers are focusing on countries like India and China where geriatric population is increasing rapidly.

Years considered for this report:

Historical Years: 2015-2018 Base Year: 2019 Estimated Year: 2020 Forecast Period: 20212025

Objective of the Study:

To analyze and forecast the market size of global regenerative medicine market. To classify and forecast global regenerative medicine market based on therapy, application, material, cell, product, technique, distribution channel and regional distribution. To identify drivers and challenges for global regenerative medicine market. To examine competitive developments such as expansions, new product launches, mergers & acquisitions, etc., in global regenerative medicine market. To conduct pricing analysis for global regenerative medicine market. To identify and analyze the profile of leading players operating in global regenerative medicine market. The analyst performed both primary as well as exhaustive secondary research for this study.Initially, the analyst sourced a list of manufacturers across the globe.

Subsequently, the analyst conducted primary research surveys with the identified companies.While interviewing, the respondents were also enquired about their competitors.

Through this technique, the analyst could include the manufacturers which could not be identified due to the limitations of secondary research. The analyst examined the manufacturers, distribution channels and presence of all major players across the globe. The analyst calculated the market size of global regenerative medicine market using a bottom-up approach, wherein data for various end-user segments was recorded and forecast for the future years. The analyst sourced these values from the industry experts and company representatives and externally validated through analyzing historical data of these product types and applications for getting an appropriate, overall market size.

Various secondary sources such as company websites, news articles, press releases, company annual reports, investor presentations and financial reports were also studied by the analyst.

Key Target Audience:

Regenerative medicine manufacturers, suppliers, distributors and other stakeholders Government bodies such as regulating authorities and policy makers Organizations, forums and alliances related to regenerative medicines Market research and consulting firms The study is useful in providing answers to several critical questions that are important for the industry stakeholders such as manufacturers, suppliers, partners, end users, etc., besides allowing them in strategizing investments and capitalizing on market opportunities.

Report Scope:

In this report, global regenerative medicine market has been segmented into following categories, in addition to the industry trends which have also been detailed below: Market, By Therapy: o Cell-Based Immunotherapy & Cell Therapy o Gene Therapy o Tissue-Engineering o Immunomodulation Therapy o Blood Transfusion o Bone Marrow Transplantation o Plasma Rich Plasma Therapy o Prolotherapy o Others Market, By Application: o Musculoskeletal Disorders o Wound Care o Oncology o Neurology o Ocular Disorders o Diabetes o Cardiology o Others Market, By Material: o Synthetic Material - Biodegradable Synthetic Polymers - Scaffold - Artificial Vascular Graft Materials - Hydrogel Materials o Biologically Derived Material - Collagen - Xenogeneic Material o Genetically Engineered Material - Genetically Manipulated Cells - 3D Polymer Technology - Transgenic - Fibroblast - Neural Stem Cells - Gene-activated Matrices o Pharmaceutical - Small Molecules - Biologics Market, By Cell: o Autologous o Allogenic Market, By Product: o Biologic o Cell -based Medical Devices o Biopharmaceutical o Biomaterial Market, By Technique: o Microfracture o Mosaicplasty Market, By Distribution Channel: o Hospitals o Clinics o Online o Others Market, By Region: o North America - United States - Canada - Mexico o Europe - Germany - France - United Kingdom - Italy - Spain o Asia-Pacific - China - Japan - India - South Korea - Australia o Middle East & Africa - South Africa - Saudi Arabia - UAE o South America - Brazil - Argentina - Colombia

Competitive Landscape

Company Profiles: Detailed analysis of the major companies present in global regenerative medicine market.

Available Customizations:

With the given market data, we offers customizations according to a companys specific needs. The following customization options are available for the report:

Company Information

Detailed analysis and profiling of additional market players (up to five).

Read the full report: https://www.reportlinker.com/p05916746/?utm_source=GNW

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Global Regenerative Medicine Market By Therapy, By Application, By Material, By Cell, By Product, By Technique, By Distribution Channel, By Region,...

Batten disease is a family of 13 rare, genetically distinct conditions. Collectively, they are the most prevalent cause of neurodegenerative disease in children, affecting 1 in 12,500 live births in the U.S. One of the Batten disease genes is CLN6. How mutations in this gene lead to the disease has been a mystery, but a study led by researchers at Baylor College of Medicine and published in the Journal of Clinical Investigation reveals how defective CLN6 can result in Batten disease.

People with Batten disease have problems with their cells ability to clear cellular waste, which then accumulates to toxic levels, said first author Dr. Lakshya Bajaj, who was working on this project while a doctorate student in the laboratory of Dr. Marco Sardiello at Baylor. Bajaj is currently a post-doctoral associate at Harvard Medical School.

In cells, lysosomes process cellular waste. They are sacs containing enzymes, a type of proteins that break down waste products into its constituent components that the cell can recycle or discard. In Batten disease caused by mutations in CLN6, the lysosomes do not process waste effectively for unknown reasons. This results in waste accumulation. Batten disease is a type of lysosomal storage disorder. Although all types of cells can be affected by defects in lysosomal waste management, brain cells, neurons, are particularly susceptible.

Waste accumulation in neurons perturbs many cellular processes and eventually results in cell death. This leads to the progressive degeneration of motor, physical and intellectual abilities observed in Batten disease patients, Bajaj said.

CLN6: another piece of the Batten disease puzzle

The connection of CLN6 with Batten disease was a bit of a mystery. This protein is not found in lysosomes, but in the endoplasmic reticulum, a structure inside cells where proteins, including lysosomal enzymes, are made. The endoplasmic reticulum is separate from the lysosomes. So, how do defects in a protein located outside of the lysosomes interfere with lysosomal function?

The Sardiello lab had previously solved a similar mystery involving CLN8, another protein located in the endoplasmic reticulum and whose mutations also cause a type of Batten disease.

We showed that CNL8 assists on the exit of lysosomal enzymes from the endoplasmic reticulum en route to the lysosomes. When CLN8 is defective, the transport of enzymes from their place of synthesis to the final destination is deficient and the lysosomes end up having fewer enzymes to work with, said Sardiello, associate professor of molecular and human genetics at Baylor and corresponding author of this work.

CLN6 and CLN8 work together

The clinical manifestations of Batten disease caused by CLN8 mutations and those of Batten disease due to defective CLN6 are remarkably similar. This and other evidence led the researchers to suspect that CLN6 and CLN8 might be working together.

Their investigations revealed that CLN6 and CLN8 do interact with each other forming a molecular complex that collects lysosomal enzymes at the endoplasmic reticulum and mediates their trafficking towards the lysosomes.

We propose that CLN8 and CLN6 together herd the enzymes into a hub, a sort of bus stop. Then, CLN8 escorts the enzymes on the bus en route to the lysosomes, while CLN6 remains at the bus stop. CLN8 returns to the bus stop after delivering the enzymes, and they repeat the process, Bajaj said. When CLN6 is defective, the enzymes are not effectively herded into the bus stop and fewer are transported to the lysosomes.

The researchers are interested in finding whether other factors are involved in transporting enzymes to the lysosomes. For instance, whether there are other bus conductors or herders of lysosomal enzymes involved that, if defective, may also contribute to Batten disease.

Other contributors to this work include Jaiprakash Sharma, Alberto di Ronza, Pengcheng Zhang, Aiden Eblimit, Rituraj Pal, Dany Roman, John R. Collette, Clarissa Booth, Kevin T. Chang, Richard N. Sifers, Sung Y. Jung, Jill M. Weimer, Rui Chen and Randy W. Schekman. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine; Texas Childrens Hospital; University of California, Berkeley; Sanford Research, Sioux Falls, South Dakota; and Sanford School of Medicine at the University of South Dakota.

This work was supported by NIH grants NS079618 and GM127492 and grants from the Gwenyth Gray Foundation, Beyond Batten Disease Foundation and NCL-Stiftung. This project was supported in part by IDDRC grant number 1U54 HD083092 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Integrated Microscopy Core and the Proteomics Core at Baylor College of Medicine with funding from NIH (DK56338, and CA125123), CPRIT (RP150578, RP170719), the Dan L Duncan Comprehensive Cancer Center and the John S. Dunn Gulf Coast Consortium for Chemical Genomics.

Read the original:
Solving the CNL6 mystery in Batten disease - Milwaukee Community Journal

SAN CARLOS, Calif., July 01, 2020 (GLOBE NEWSWIRE) -- BioCardia, Inc. [NASDAQ:BCDA], a leader in the development of comprehensive solutions for cardiovascular regenerative therapies, today announced activation of a pivotal trial studying the Companys investigational CardiAMP cell therapy in the treatment of chronic myocardial ischemia (CMI), as well as completion of the first site initiation visit in the trial.

The CardiAMP CMI Trial is studyingCardiAMP cell therapy, an autologous cell therapy formulation designed to stimulate the bodys natural healing response for the treatment of refractory angina, estimated to impact between 600,000 and 1,800,000 patients in the United States.1 It has been reported that these patients suffer from poor perceived health status and psychological distress, have significant impairments in quality of life, and represent a burden to the health care system due to significant resource use.2

The study has been approved by the FDA to enroll up to 343 patients at up to 40 centers. The purpose of the study is to determine the safety and efficacy of CardiAMP cell therapy in the treatment of patients with refractory angina pectoris and CMI. The FDA has said that the trial qualifies as a pivotal trial to produce the primary data to support market registration for the CardiAMP cell therapy for this significant unmet clinical need.

The Center for Medicare and Medicaid Services (CMS) will reimburse investigational sites for patient screening, patient treatment, the investigational cell therapy product, and standard of care follow-up visits at a level similar to that being provided for the ongoing pivotal CardiAMP Heart Failure Trial.

The first site initiation visit took place last week at the University of Florida at Gainesville, under the leadership of R. David Anderson, MD. Patient recruitment is expected to begin shortly.

We are pleased to be activating a second pivotal trial for the CardiAMP cell therapy and expanding our relationship with the clinical research team at the University of Florida under the guidance of Dr. Anderson, who is also the site principal investigator of the ongoing CardiAMP Heart Failure Trial and a world class interventional cardiologist, said BioCardia Chief Executive Officer Peter Altman, Ph.D. We are also delighted to announce the experienced and distinguished executive steering committee for the trial, which includes Dr. Timothy Henry of The Christ Hospital, Dr. Carl Pepine of the University of Florida, Dr. Amish Raval of the University of Wisconsin, and Dr. Bernard Gersh of the Mayo Graduate School of Medicine.

Based on our experience with 75 patients randomized in the CardiAMP Heart Failure trial, the effective CD34+ cell dosage in the CardiAMP Chronic Myocardial Ischemia trial is likely to be greater than the effective CD34+ dosage advanced in previously published trials for selected CD34+ cells which demonstrated compelling clinical results, said BioCardia Chief Medical Officer Eric Duckers, M.D. 3 This is possible with patient selection, efficient delivery, and point of care cell processing, which are the pillars of the CardiAMP therapy.

For additional information, please visit http://www.clinicaltrials.gov.

About BioCardia:BioCardia, Inc., headquartered in San Carlos, CA, is developing regenerative biologic therapies to treat cardiovascular disease. CardiAMP autologous and NK1R+ allogenic cell therapies are the Companys biotherapeutic platforms in clinical development. The Company's products include theHelix biotherapeutic delivery system and its steerable guide and sheath catheter portfolio.BioCardia also partners with other biotherapeutic companies to provide its Helix system and clinical support to their programs studying therapies for the treatment of heart failure, chronic myocardial ischemia and acute myocardial infarction. For more information, visit http://www.BioCardia.com.

Forward Looking Statements:This press release contains forward-looking statements that are subject to many risks and uncertainties. Forward-looking statements include references to future enrollment and cell dosage in this second pivotal clinical trial and statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations. Such factors include, among others, the inherent uncertainties associated with developing new products or technologies and obtaining regulatory approvals. These forward-looking statements are made as of the date of this press release, and BioCardia assumes no obligation to update the forward-looking statements.

INVESTOR CONTACT:David McClung, Chief Financial Officerinvestors@BioCardia.com, (650) 226-0120

MEDIA CONTACT:Michelle McAdam, Chronic Communications, Inc.michelle@chronic-comm.com, (310) 902-1274

Original post:
BioCardia Announces Activation of Pivotal Trial Studying CardiAMP Cell Therapy Trial to Treat Chronic Myocardial Ischemia - GlobeNewswire

Global Stem Cell Banking Market: Overview

The demand within the global stem cell banking market is growing on account of advancements in the field of regenerative medicine. The medical fraternity has become extremely focused towards the development of artificial tissues that can infuse with the human body. Furthermore, medical analysis and testing has gathered momentum across biological laboratories and research institutes. Henceforth, it is integral to develop stem cell samples and repositories that hold relevance in modern-day research. The need for regenerative medicine emerges from the growing incidence of internal tissue rupture. Certain types of tissues do not recover for several years, and may even be damaged permanently. Therefore, the need for stem cell banking is expected to grow at a significant pace.

Download Brochure of This Market Report at https://www.tmrresearch.com/sample/sample?flag=B&rep_id=6111

In a custom report, TMR Research digs into the factors that have aided the growth of the global stem cell banking market. The global stem cell banking market can be segmented on the basis of bank size, application, and region. The commendable developments that have incepted across the US healthcare industry has given a thrust to the growth of the North America stem cell banking market.

Global Stem Cell Banking Market: Notable Developments

The need for improved regenerative medication and anatomy has played an integral role in driving fresh developments within the stem cell banking market.

Gallant has emerged as a notable market entity that has remained as the torchbearer of innovation within the global stem cell banking market. The company has recently launched stem cell banking for dogs, and has attracted the attention of the masses. As people become increasingly concerned about their pets, the new move by Gallant shall help the company in earning the trust of the consumers. Moreover, it can move several notches higher on the innovation index.

Cells4Life has also remained at the forefront of developments within the global stem cell banking market. After suffering backlash for its error in cord blood stem cell promotion, the company is expected to use effective public relation strategies to regain its value in the market.

Global Stem Cell Banking Market: Growth Drivers

Development of improved facilities for storage of stem cells has played an integral role in driving market demand. Furthermore, the unprecedented demand for improved analysis of regenerative medications has also created new opportunities within the global stem cell banking market. Medical research has attracted investments from global investors and stakeholders. The tremendous level of resilience shown by biological researchers to develop stem cell samples has aided market growth. Henceforth, the total volume of revenues within the global stem cell banking market is slated to multiply.

Commercialization of stem cell banks has emerged as matter of concern for the healthcare industry. However, this trend has also helped in easy storage and procurement of cells stored during the yester years of children. Presence of sound procedures to register at stem cell banks, and the safety offered by these entities, has generated fresh demand within the global market. New regional territories are opening to the idea of stem cell banking. Several factors are responsible for the growth of this trend. Primarily, improvements in stem cell banking can have favourable impact on the growth of the healthcare industry. Moreover, the opportunities for revenue generation associated with the development of functional stem cell banks has aided regional market growth.

The global stem cell banking market is segmented on the basis of:

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Stem Cell Banking Market Global Industry Analysis and Opportunity and Forecast 2018 to 2028 - Cole of Duty

The reports seemed to take doctors by surprise: The respiratory virus that causes Covid-19 made some patients nauseous. It left others unable to smell. In some, it caused acute kidney injury.

As the pandemic grew from an outbreak affecting thousands in Wuhan, China, to some 10 million cases and 500,000 deaths globally as of late June, the list of symptoms has also exploded. The Centers for Disease Control and Prevention constantly scrambled to update its list in an effort to help clinicians identify likely cases, a crucial diagnostic aid at a time when swab tests were in short supply and typically took (and still take) days to return results. The loss of a sense of smell made the list only in late April.

For many diseases, it can take years before we fully characterize the different ways that it affects people, said nephrologist Dan Negoianu of Penn Medicine. Even now, we are still very early in the process of understanding this disease.

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What they are understanding is that this coronavirus has such a diversity of effects on so many different organs, it keeps us up at night, said Thomas McGinn, deputy physician in chief at Northwell Health and director of the Feinstein Institutes for Medical Research. Its amazing how many different ways it affects the body.

One early hint that that would be the case came in late January, when scientists in China identified one of the two receptors by which the coronavirus, SARS-CoV-2, enters cells. It was the same gateway, called the ACE2 receptor, that the original SARS virus used. Studies going back some two decades had mapped the bodys ACE2 receptors, showing that theyre in cells that line the insides of blood vessels in what are called vascular endothelial cells in cells of the kidneys tubules, in the gastrointestinal tract, and even in the testes.

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Given that, its not clear why the new coronavirus ability to wreak havoc from head to toe came as a surprise to clinicians. Since ACE2 is also the receptor for SARS, its expression in other organs and cell types has been well-known, said Anirban Maitra of MD Anderson Cancer Center, who led a study mapping the receptor in cells of the GI tract. (Maitra is an expert in pancreatic cancer and, like many scientists this year, added Covid-19 to his research.)

Infecting cells is only the first way SARS-CoV-2 wreaks havoc. Patients with severe Covid-19 also suffer a runaway inflammatory response and, often, clot formation, said infectious disease physician Rochelle Walensky of Massachusetts General Hospital. That can cause symptoms as different as a lack of blood flow to the intestines and the red, inflamed Covid toe.

Weve had five cases of patients whove had to have their gut removed, Walensky said. You see these cases and you say, wait a minute; the virus is doing this, too? It has definitely been keeping us on our toes.

Venky Soundararajan had a hunch that the extent of ACE2 distribution throughout the body was lying in plain sight. The co-founder and chief scientific officer of nference, which uses artificial intelligence to mine existing knowledge, he and his colleagues turned their system into a hunt for ACE2 knowledge. Combing 100 million biomedical documents from published papers to genomic and other -omics databases, they uncovered multiple tissues and cell types with ACE2 receptors, they reported last month in the journal eLife.

They also calculated what percent of each cell type expresses reasonable amounts of ACE2, Soundararajan said. On average, about 40% of kidney tubule cells do, and in a surprise for a respiratory virus, cells in the GI tract were the strongest expressors of ACE2 receptors, he said.

The data mining found that ACE2 is also expressed in the noses olfactory cells. Thats not a new finding per se the nference system found it in existing databases, after all but it hadnt been appreciated by scientists or clinicians. It explains the loss or altered sense of smell that Covid-19 patients experience. Its importance became clear earlier this month, when scientists at the Mayo Clinic and nference reported that loss of a sense of smell is the earliest signature of Covid-19, appearing days before a positive swab test.

That study, using health records of 77,167 people tested for Covid-19, showed how the assumption that infection would first and foremost cause respiratory symptoms was misplaced. In the week before they were diagnosed, Covid-19 patients were 27 times more likely than people who tested negative for the virus to have lost their sense of smell. They were only 2.6 times more likely to have fever or chills, 2.2 times more likely to have trouble breathing or to be coughing, and twice as likely to have muscle aches. For months, government guidelines kept people not experiencing such typical signs of a respiratory infection from getting tested.

Faced with a disease the world had never seen before, physicians are learning as they go. By following the trail of ACE2 receptors, they are more and more prepared to look for, and treat, consequences of SARS-CoV-2 infection well beyond the obvious:

Gut: The coronavirus infects cells that line the inside of the large and small intestine, called gut enterocytes. That likely accounts for the diarrhea, nausea, and abdominal pain that about one-third of Covid-19 patients experience, said MD Andersons Maitra: The GI symptoms reflect physiological [dysfunction] of cells of the lower GI tract.

Why dont all patients have GI symptoms or indeed, the whole panoply of symptoms suggested by the near ubiquity of ACE2 receptors? For those with mild to moderate Covid-19, the infectious load in the GI tract may simply not be sufficient to cause symptoms, Maitra said.

Kidney: The cells lining the tubules that filter out toxic compounds from the blood are rife with ACE2 receptors. Last month, scientists studying 1,000 Covid-19 patients at a New York City hospital reported that 78% of those in intensive care developed acute kidney injury.

Smell: An analysis of 24 studies with data from 8,438 Covid-19 patients from 13 countries found this month that 41% had lost their sense of taste or smell, or both. That shouldnt be surprising, said Fabio Ferreli of Humanitas University in Milan: Perhaps the highest levels of ACE2 receptors are expressed in cells in the nasal epithelium. The sensory loss isnt due to nasal inflammation, swelling, or congestion, he said, but to direct damage to these epithelial cells. Loss of smell also impacts taste, but the virus may also have a direct effect on taste: The nference analysis found high levels of the ACE2 gene in tongue cells called keratinocytes, which contribute to the sense of taste.

There is another implication of the high expression of ACE2 in olfactory epithelium cells, scientists at Johns Hopkins concluded in a paper posted to the preprint site bioRxiv last month: ACE2 levels in the olfactory epithelium of the upper airways that are 200 to 700 times higher than in the lower airways might explain the viruss high transmissibility. It was weeks before experts recognized that the virus could spread from person to person.

Lungs: This is where a respiratory virus should strike, and SARS-CoV-2 does. The lungs type II alveolar cells among other jobs, they release a compound that allows the lungs to pass oxygen to the blood and take carbon dioxide from it are studded with ACE2 receptors. Once infected with the coronavirus, they become dysfunctional or die, and are so swarmed by immune cells that this inflammatory response can explode into the acute respiratory distress syndrome (ARDS) that strikes many patients with severe Covid-19, Walensky said.

There is new evidence that the virus also attacks platelet-producing cells, called megakaryocytes, in the lungs. In a study published on Thursday, pathologist Amy Rapkiewicz of NYU Winthrop Hospital found something she had never seen before: extensive clotting in the veins and other small blood vessels of patients hearts, kidneys, liver, and lungs. She suspects that the platelets produced by infected megakaryocytes travel through the bloodstream to multiple organs, damaging their vasculature and producing potentially fatal clots. You see that and you say, wow, this is not just a respiratory virus,' Rapkiewicz said.

Pancreas: In April, scientists in China reported that there was higher expression of the gene for ACE2 in the pancreas than in the lungs. Genetic data are an indirect measure of ACE2 receptors themselves, but could have been a tip-off to physicians to monitor patients for symptoms there. As it happens, the Chinese researchers also found blood markers for pancreas damage in Covid-19 patients, including in about 17% of those with severe disease.

Heart: Patients with severe Covid-19 have a high incidence of cardiac arrests and arrhythmias, scientists at the Perelman School of Medicine at the University of Pennsylvania recently found. Thats likely due to an extreme inflammatory response, but there might be more direct effects of the coronavirus, too. A large team of European researchers reported in April that arrhythmia (including atrial fibrillation), heart injury, and even heart failure and pulmonary embolism might reflect the fact that ACE2 receptors are highly expressed in cells along the inside walls of capillaries. When these vascular endothelial cells become infected, the resulting damage can cause clots, MGHs Walensky said, which in turn can cause Covid toe, strokes, and ischemic bowel (too little blood flow to the gut). Studies from around the world suggest that 7% to 31% of Covid-19 patients experience some sort of cardiac injury.

Gallbladder: Specialized cells in this organ, too, have high levelsof ACE2 receptors. Damage to the gallbladder (like the pancreas) can cause digestive symptoms.

With the number of Covid-19 patients closing in on 10 million, physicians fervently hope the virus has no more surprises in store. But theyre not counting on it.

Ive seen patients every day during this crisis, said Northwells McGinn. There have been times when Ive said, wait, the virus cant do anything new and then theres a young woman with a stroke or an older man with myocarditis, inflammation of the heart muscle. I keep thinking Im going to run out of material for the teaching videos he does on Covid-19, but it hasnt happened.

Correction: An earlier version of the video misstated how SARS-CoV-2 replicates inside cells it infects.

The rest is here:
Not just the lungs: Covid-19 attacks like no other 'respiratory' virus - STAT

Cancer metastasis is all about rogue cancer cells abandoning the original tumor and venturing through the blood in search for new breeding grounds. Sometimes, single cells take the risk, but other times cancer cells detach from the tumor as clusters.

Scientific evidence shows that clusters seem to be more successful at metastasis than single cells and recent work from the laboratory of Dr. Xiang Zhang sheds new light into what contributes to the clusters enhanced metastatic abilities.

We were working with different animal models investigating why tumor clusters seemed to be better at forming lung metastases than single cells, when we unexpectedly discovered that the clusters ability to metastasize appeared to be associated with the presence of competent natural killer (NK) cells, said first author Hin Ching Flora Lo, graduate student in Baylors Integrative Molecular and Biomedical Sciences Graduate Program in the Zhang lab. Zhang is professor of molecular and cellular biology and the Lester and Sue Smith Breast Center at Baylor.

The researchers determined that activated NK cells, immune cells that specialize in surveillance and destruction of tumor cells, can eliminate both single cell and cluster metastasis, but they are more efficient at eliminating the former. The clusters have a selective advantage and, as a result, their contribution to metastasis is higher than that of single cancer cells.

We also explored what mediated the clusters resistance to NK cell killing and discovered that cancer clusters seem to tone down the activity of NK cells against them, Lo said. Clusters display on the cell surface more molecules that inhibit the activity of NK cells and fewer that increase their activity. As a result, when NK cells bind to clusters to destroy them, the combined effect is reduced killing activity.

This phenomenon may represent an additional survival advantage complementary to other previously known characteristics of cancer clusters, such as being resistant to chemotherapy.

Our study highlights the importance of NK cells in immunotherapy. Activated NK cells act fast, and efficiently kill tumor cells. They use a killing mechanism that is similar to the one T cells use, but recognition of the tumor cells is different, said Zhang, a member of Baylors Dan L Duncan Comprehensive Cancer Center and a McNair Scholar.

Thats one of the reasons we think that enhancing NK-mediated killing ability may provide a complementary approach in immunotherapy, Zhang said.

Interested in reading all the details of this study? Find it in the journal Nature Cancer.

Other contributors to this work include Zhan Xu, Ik Sun Kim, Bradley Pingel, Sergio Aguirre, Srikanth Kodali, Jun Liu, Weijie Zhang, Aaron M. Muscarella, Sarah M. Hein, Alexander S. Krupnick, Joel R. Neilson, Silke Paust, Jeffrey M. Rosen and Hai Wang. The authors are affiliated with Baylor College of Medicine, Courier Therapeutics, Texas Medical Center, University of Virginia, The Scripps Research Institute and the McNair Medical Institute.

This study was supported by the Breast Cancer Research Foundation, National Cancer Institute grants (CA227904, NCI CA148761, NCI CA190467), U.S. Department of Defense (DAMD W81XWH-16-1-0073 and W81XWH-18-1-0574) and the McNair Medical Institute. Further support was provided by CPRIT RP170172, CPRIT Core Facility Support Award (CPRIT-RP180672), The Samuel Waxman Cancer Research Foundation and NIH grants (P01 AI116501, R01 AI145108-01, IO1 IBX0104588A, R41 CA224520-01A1, P30 CA125123, S10 RR024574 and 1S10OD016167).

By Ana Mara Rodrguez, Ph.D.

Read the original here:
The single cell and the cluster, what makes one better than the other at cancer metastasis? - Baylor College of Medicine News