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Environmental Defense Fund: Sustainable farming, feeding growing population require biotechnology – Genetic Literacy Project

Posted: June 21, 2017 at 10:44 am

It is critical that humanity meet the food needs of a growing population and relieve the increasing pressures on natural systems. Environmental Defense Fund supports the coexistence of diverse farming systems to ensure a sustainable future for farmers, society, and our environment. Achieving these goals will require a comprehensive strategy that draws on a wide range of approaches and technologies, including biotechnology.

EDF recognizes the use of biotechnology as a legitimate deployment of science in the search for effective solutions, and also recognizes that past deployment of some biotechnology products has caused legitimate concerns. For that reason, we will support or oppose specific biotechnology products or processes based on transparent assessments of their health, environmental, social, and economic risks and benefits.The risks and benefits of biotechnology products will often vary by organism, geography and other variables, and need to be assessed at relevant temporal and spatial scales.

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Global Pharmaceutical & Biotechnology Environmental Monitoring Market 2017 Danaher Corporation, Thermo Fisher … – Aperture Games

Posted: June 21, 2017 at 10:44 am

The Report describe Pharmaceutical & Biotechnology Environmental Monitoring Introduction, product scope, market overview, opportunities, risk, driving force also to analyze the top manufacturers, with sales, revenue, and price, market type and application, with sales market share and growth rate by type, application, from 2017 to 2022

Global Pharmaceutical & Biotechnology Environmental Monitoring Industry 2017 presents an executive level blueprint of the global Pharmaceutical & Biotechnology Environmental Monitoring market. This is an analytical research report that delves into evaluating the dynamics of the global Pharmaceutical & Biotechnology Environmental Monitoring market drawing reference to the key trends shaping the supply-chain pattern of the industry. To study the exhaustive information sourced from detailed primary and secondary research, the analysts of the report have used industry leading analytical tools such as SWOT analysis and Porters five forces. The observation made from the analysis not only helps analysts to compile a comprehensive report on the global Pharmaceutical & Biotechnology Environmental Monitoring market, but the same also assists them to understand the prevailing competitive landscape of the market.

For a study to be beneficial for stakeholders, it should constitute a detailed research on the market competitiveness. For the purpose of the same, the research report profiles the leading and prominent players in the Pharmaceutical & Biotechnology Environmental Monitoring market. Information pertaining to key strategies adopted by these companies has been obtained from their respective financial reports, and a meticulous study on the market trends that has impacted their plan of action. Results achieved from the strategies is analyzed thoroughly in the report to update stakeholders about the trends impacting the market. Key findings of the report on the global Pharmaceutical & Biotechnology Environmental Monitoring market will also help companies operating in the market to identify the growth opportunities to propel their operations.

To provide a comprehensive report of the global Pharmaceutical & Biotechnology Environmental Monitoring market, the study has segmented it on the basis of product types, applications, end-use industries, and geography. The leading geographic segments is identified in the report, which also studies the prospects exhibited by the emerging regional markets. With an aim of presenting a 360 degree overview of the market, the report studies the growth drivers, market restraints, and opportunities in detail. Based on in-depth study, the report presents refined growth forecasts for the Pharmaceutical & Biotechnology Environmental Monitoring market.

An exhaustive qualitative review of the factors accelerating and restraining the growth of the Pharmaceutical & Biotechnology Environmental Monitoring market and approaching opportunities has been deployed. The Pharmaceutical & Biotechnology Environmental Monitoring market has been analyzed based on applications, geographic distribution, and the substantial factors accountable for the rising demand of the Pharmaceutical & Biotechnology Environmental Monitoring market globally have been detailed in this report. The report covers the global Pharmaceutical & Biotechnology Environmental Monitoring market right from its definition to the numerous categorizations of the market as well as its key end-use applications.

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The elementary weaknesses and strengths of the leading vendors coupled with the rate of growth for each of the segments of the Pharmaceutical & Biotechnology Environmental Monitoring worldwide market have been conferred after a complete analysis of past and prospective trends, regulatory needs, and technological innovations.

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Mayo Clinic Ventures funds new cancer-fighting cell, gene therapy – Post-Bulletin

Posted: June 21, 2017 at 10:42 am

SAN FRANCISCO, Calif. Mayo Clinic Ventures has partnered with a California-based company to make cancer-fighting gene therapies available to the public.

Vineti, a pioneering cell and gene therapy software and analytics company, announced Tuesday that it had completed its initial round of funding raising $13.75 million aimed at delivering "the first cloud-based software solution to improve patient access, accelerate life-saving treatment delivery, and promote safety and regulatory compliance for individualized cell therapies."

The funding was provided by Mayo Clinic Ventures, GE Ventures, DFJ and LifeForce Capital. It's just the 15th company that Mayo Clinic Ventures has backed since it was formed, according to Andy Danielson, vice chairman of Mayo Clinic Ventures.

"One thing with Vineti that we liked is that we have a commitment to cell and gene therapies at Mayo," Danielson told TechCrunch.com. "Vineti will make the gene and cell therapy production process more efficient and as a result, less costly. It's all part of the equation of making these therapies more affordable and opening them up to a greater number of people."

The targeted cancer therapy under development by Vineti is part of a thriving field that conducted more than 800 clinical trials in 2016 while investing nearly $6 billion. It's all aimed at positively impacting the oncology field, the largest market in medicine that's expected to grow to $165 billion by 2021.

The first two cell therapies are expected to hit the market later this year.

Vineti touts its plans as one that "integrates logistics, manufacturing and clinical data to improve product performance overall and enable faster, broader access for patients."

"Physicians, medical researchers and pharmaceutical companies are working together to develop successful therapies, transitioning from a one-size-fits-all model to individualized treatments for each patient," said Amy DuRoss, CEO at Vineti. "Now, the process for creating and delivering these treatments can be as innovative as the therapies themselves. We are developing the Vineti platform to help these treatments reach the patients who need them the most, and are confident the partnership between our advances technologies and leading medical research will deliver better outcomes across the globe."

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Stem cell therapy relying on patient’s own unhealthy heart may be dangerous – Genetic Literacy Project

Posted: June 21, 2017 at 10:42 am

A new study at Tel Aviv University shows that stem cell therapy, one of the few treatments available to patients with severe and end-stage heart failure, can actually harm them unless it is done differently.

We concluded that stem cells used in cardiac therapy should be drawn from healthy donors or be better genetically engineered for the patient, said lead researcher Jonathan Leor of the universitys Sackler Faculty of Medicine and Sheba Medical Center.

Doctors use tissue or adult stem cells to replace damaged tissue, which encourages regeneration of blood vessel cells and new heart muscle tissue. But cardiac stem cells from a diseased heart can lead to a toxic interaction via a molecular pathway between the heart and the immune system, the study found.

We found that, contrary to popular belief, tissue stem cells derived from sick hearts do not contribute to heart healing after injury, Leor said. Furthermore, we found that these cells are affected by the inflammatory environment and develop inflammatory properties. The affected stem cells may even exacerbate damage to the already diseased heart muscle.

[Read the fully study here (behind paywall)]

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British Biotech Tops up its Cancer Pipeline with New TCR Therapy – Labiotech.eu (blog)

Posted: June 21, 2017 at 10:42 am

Cell Medica just acquired Catapult Therapy TCR, set up by UKs CGT Catapult, gaining the rights to its TCR therapy candidate to treat solid tumors.

Cell Medica says its all set to leverage itsDominant T cell receptor (TCR) platform technology, which the company licensed from University College London (UCL) last year, toenhance existing T cell therapies for the treatment of solid tumors. The company justacquiredCatapult Therapy TCR, a subsidiary of Cell and Gene Therapy (CGT) Catapult for its WT1-TCR therapy. Now, Cell Medica plans to showcase its technology by upgrading the new TCR candidate to treat solid tumors such asmesothelioma and ovarian cancer.

The WT1-TCR therapy resulted from earlier research at UCL and the Imperial College London and was spun out into a companyby CGT Catapult, UCL Business, and Imperial Innovations. The technology hinges on engineering the patients own T cells to target the WT1-antigen, which is expressed in a number of cancers.

While CGT catapult has already advanced the immuno-oncology candidate through Phase I/II to treat blood cancers, Cell Medica plans to retool the candidate using its Dominant TCR technologyand expects to start clinical trials with the upgraded WT1-TCR version in late 2018 to treat solid tumors.

Our objective is to show how we can enhance any existing TCR cell therapy with the Dominant TCR technology to create a more effective treatment for patients with solid tumors who otherwise have a very poor prognosis, commentedGregg Sando, CEO of Cell Medica, in a press release.

No financial details of the new deal were disclosed, but CGT Catapult will remain involved. Cell Medica is also setting up its cell therapy manufacturingat CGT Catapults GMP manufacturing facility in Stevenage, UK, where the two will work to develop a commercial scale production process

Apart from its recent deal with UCL, Cell Medica has also bolstered its pipeline with the acquisition of Delenex last year, to advance the biotechs assets in the CAR-T field. The company has also partnered up with the infamous Baylor College of Medicine, toexplore the use of allogeneic, off-the-shelf,Natural Killer T (NKT) cells.

Establishing a solid technology base could improve Cell Medicas chances within the over-crowded and unpredictable immuno-oncology space, where it will have to compete against biotech success stories like Adaptimmune or Cellectis.

Images via shutterstock.com /xrenderandcellmedica.com

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‘Protective shield’ for beta-cells suggests new option to treat diabetes – Medical Xpress

Posted: June 21, 2017 at 10:42 am

June 21, 2017 Credit: Medical University of Vienna

The islets of Langerhans in the human pancreas produce and release insulin to regulate blood glucose levels. Insulin, which is specifically produced in b-cells, serves to prompt cells to take up glucose circulating in blood. Thus, insulin release lowers the level of glucose in blood. In diabetes, this cycle is disrupted by the premature death of b-cells. Working with an international team of researchers, Katarzyna Malenczyk from the Department of Molecular Neurosciences at MedUni Vienna's Center for Brain Research showed in the study published in the EMBO Journal today that the loss of a key protein, secretagogin, triggers the death of b-cells and, conversely, that these cells can be protected by increasing the amount of this protein in those suffering from diabetes.

"Although researchers have been trying for decades to find effective means of protecting b-cells in diabetes, we still haven't found curative therapies. Understanding the mechanism that could lead to the development of a medication is therefore of enormous value," says Dr. Malenczyk, lead author of a new study. "We were able to show in animal models and also in b-cells from diabetic donors that, in disease conditions the level of secretagogin is significantly reduced, suggesting a direct correlation between this protein and the severity of the disease," explains Tibor Harkany, Head of the Department of Molecular Neurosciences of MedUni Vienna's Center for Brain Research. "If we find molecular tools to keep b-cells active, we could also ensure their survival."

So far, research on the protein secretagogin has been limited. Yet, Dr. Malencyzk and an international team led by the Department of Molecular Neurosciences at the Center for Brain Research have now discovered that the presence of this protein is critical for bcells to remain healthy, and therefore represents a target for the development of an effective treatment for diabetes whether prevention or therapy at clinical onset is considered.

Mechanism explained

The most important outcome of this study is to show that secretagogin regulates whether and how b-cells shed all those proteins that are no longer required or useful to maintain their physiological integrity and functions. Professor Harkany remarks: "If secretagogin is turned off, toxic proteins as waste products can rapidly accumulate in bcells and this inevitably leads to their death." And so, if levels of secretagogin in b-cells could be boosted in diabetes to remain near-physiological, this would offer an attractive avenue of their self-protection.

Secretagogin a Viennese discovery

The protein secretagogin was first identified by Ludwig Wagner (Department of Medicine III), who is also co-author of the current paper, in Vienna in 2000. Seventeen years later, the present study demonstrates the exact role of this protein. Professor Wagner says: "It is nail-biting to see that our continued study of this single protein has reached a stage where the molecular understanding of its function can realize the development of new treatment options."

Fuelling secretagogin levels

But how can cellular levels of this protein be boosted in diabetes? Dr. Malenczyk and the international research team around her showed that the protein can be retained in diabetes and its activity increased by stimulating TRPV ion channels. TRPV1 is a transmembrane protein that besides the nervous system is also expressed in pancreatic beta-cells. If this receptor is stimulated, more secretagogin is being produces in b-cells. TRPV1 is easiest stimulated by capsaicin, an alkaloid that occurs in various types of bell and chilli pepper. Capsaicin binds directly to TRPV1 ion channels and by stimulating them has a profound effect on b-cell biology. Dr. Malenczyk notes: "In a first step, our discovery could be an efficient treatment for diabetes but, of course, this requires follow-up studies in human sufferers. We are cautious to suggest that that diabetics could improve their diets by consuming more peppers or chillies. TRPV1 is a promising target for potential drugs, because, in diabetes, it continues to be found with its levels largely unaltered in b-cells.

Explore further: 'Trigger' for stress processes discovered in the brain

More information: A TRPV1-to-secretagogin regulatory axis controls pancreatic beta-cell survival by modulating protein turnover. Katarzyna Malenczyk, Fatima Girach, Edit Szodorai, Petter Storm, sa Segerstolpe, Giuseppe Tortoriello, Robert Schnell, Jan Mulder, Roman A. Romanov, Erzsbet Bork, Fabiana Piscitelli, Vincenzo Di Marzo, Gbor Szab, Rickard Sandberg, Stefan Kubicek, Gert Lubec, Tomas Hkfelt, Ludwig Wagner, Leif Groop and Tibor Harkany, EMBO Journal, 2017. DOI: 10.15252/emboj.201695347

At the Center for Brain Research at the MedUni Vienna an important factor for stress has been identified in collaboration with the Karolinska Institutet in Stockholm (Sweden). This is the protein secretagogin that plays an ...

Pancreatic beta cells help maintain normal blood glucose levels by producing the hormone insulinthe master regulator of energy (glucose). Impairment and the loss of beta cells interrupts insulin production, leading to ...

Type-1 diabetes occurs when immune cells attack the pancreas. EPFL scientists have now discovered what may trigger this attack, opening new directions for treatments.

Diabetes continues to be a global health problem, with the number of cases projected to rise from 285 million in 2010 to nearly 400 million by the year 2030. Diabetes is the fourth leading cause of death worldwide.

Research led by a Johns Hopkins University biologist demonstrates the workings of a biochemical pathway that helps control glucose in the bloodstream, a development that could potentially lead to treatments for diabetes.

The significant role of beta cell 'hubs' in the pancreas has been demonstrated for the first time, suggesting that diabetes may due to the failure of a privileged few cells, rather than the behaviour of all cells.

Heart disease is a leading cause of death worldwide and exacerbated by type 2 diabetes, yet diabetes treatment regimens tend to focus primarily on blood sugar maintenance. This common approach to type 2 diabetes management ...

A team of researchers from Sweden, the U.S. and Switzerland has found that treating rat liver cells with a compound called sulforaphane, which is found in cruciferous vegetables, reduced production of glucose. In their paper ...

(HealthDay)For many people with diabetes, low blood sugar levels are a serious health risk, but researchers report that a new nasal powder quickly reverses the effects of this dangerous condition.

An inexpensive first-line treatment for type 2 diabetes may also reduce heart disease in those with type 1 diabetes, according to a new global trial led by the University of Glasgow.

In a landmark study, UNC School of Medicine researchers have shown that blood glucose testing does not offer a significant advantage in blood sugar control or quality of life for type 2 diabetes patients who are not treated ...

Low-income Hispanics with Type 2 diabetes who received health-related text messages every day for six months saw improvements in their blood sugar levels that equaled those resulting from some glucose-lowering medications, ...

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Researchers call for paradigm shift in type 2 diabetes treatment – Medical Xpress

Posted: June 21, 2017 at 10:42 am

June 20, 2017 Credit: CC0 Public Domain

Heart disease is a leading cause of death worldwide and exacerbated by type 2 diabetes, yet diabetes treatment regimens tend to focus primarily on blood sugar maintenance. This common approach to type 2 diabetes management can leave patients at risk for heart attack and stroke. But results from four recent randomized clinical trials suggest that using medications that offer glucose control while reducing the risk for cardiovascular disease could improve patient outcomes.

"Strong evidence provided by the four recent trials published within the past 1.5 to 2 years in the New England Journal of Medicine has shown that some of the modern available therapeutic agents that control blood glucose also help reduce the risk for cardiovascular disease," said Faramarz Ismail-Beigi, MD, PhD, Professor of Medicine at Case Western Reserve University and Endocrinologist at University Hospitals Cleveland Medical Center and Louis Stokes Cleveland VA Medical Center. "Based on this evidence, we propose that we must shift from our previous paradigm with its monocular focus on control of blood glucose and hemoglobin A1c, to one of control of blood glucose plus preventing cardiovascular disease and death from cardiovascular causes." Hemoglobin A1c is a common test used to determine a patient's average blood sugar levels over the previous 2-3 months.

Ismail-Beigi helped conduct three of the four clinical trials, and he and his collaborators recently reviewed trial results in the Journal of General Internal Medicine. The trials each tested a blood sugar-lowering medicationpioglitazone, empagliflozin, liraglutide, or semaglutidebut recruited patients with heart disease or stroke. The goal was to determine whether or not the drugs were safe, but in each study, researchers were surprised to find participants with or at risk of type 2 diabetes also experienced cardiovascular improvements.

"For the first time we have seen glucose-lowering medications that can improve cardiovascular outcomes," Ismail-Beigi said. "It is highly possible that newer agents in these classes of medications, used singly or in combination, will prove to be more efficacious in the management of type 2 diabetes and prevention of cardiovascular disease, even in patients at earlier stages of the disease process."

Previous studies focused on tight control of blood sugar have not shown major cardiovascular benefits for diabetes patients. "Strict control of blood glucose levels has shown minor, if any, positive effect on prevention of cardiovascular disease," said Ismail-Beigi. "In fact, a large NIH-funded clinical trial on type 2 diabetes management failed to show that strict control of blood glucose levels had any positive effect on cardiovascular outcomes or mortality, and in fact, may be harmful."

The new trial results could help address a major dilemma for clinicians looking for ways to control heart disease and reduce mortality, while simultaneously managing blood glucose in patients with type 2 diabetes.

Said Ismail-Beigi, "Our review focuses on the need for a paradigm shift on how we should think about management of type 2 diabetes. I believe it will necessitate a rethinking of goals and approaches by guideline committees. We also hope that the FDA might consider approving new medications for management of type 2 diabetes not only based on their safety profile and their efficacy to control blood glucose, but also whether the medication reduces overall mortality and cardiovascular-related mortality."

Explore further: Major study heralds new era in treatment of type 2 diabetes

More information: Faramarz Ismail-Beigi et al, Shifting Paradigms in the Medical Management of Type 2 Diabetes: Reflections on Recent Cardiovascular Outcome Trials, Journal of General Internal Medicine (2017). DOI: 10.1007/s11606-017-4061-7

A drug that lowers blood sugar levels for people with type 2 diabetes has also been revealed to significantly reduce the risk of both cardiovascular and kidney disease.

More work needs to be done to examine the real world effects of the commonly prescribed diabetes drug empagliflozin, new research in the journal Diabetes Therapy finds.

Researchers have shown that the glucose-lowering drug liraglutide safely and effectively decreases the overall risk of heart attack, stroke, or cardiovascular death for people with type 2 diabetes. These patients are at high ...

The health risks and mortality associated with prediabetes seem to increase at the lower cut-off point for blood sugar levels recommended by some guidelines, finds a large study published in The BMJ today.

A new study shows that the drug fenofibrate might reduce the risk of cardiovascular events in patients with type 2 diabetes who have high levels of triglycerides and low levels of "good" cholesterol, despite being treated ...

Why is heart failure not more rigorously assessed in clinical trials of antidiabetes drugs? In a Personal View, published in The Lancet Diabetes & Endocrinology journal, Professor John McMurray of The University of Glasgow ...

Heart disease is a leading cause of death worldwide and exacerbated by type 2 diabetes, yet diabetes treatment regimens tend to focus primarily on blood sugar maintenance. This common approach to type 2 diabetes management ...

A team of researchers from Sweden, the U.S. and Switzerland has found that treating rat liver cells with a compound called sulforaphane, which is found in cruciferous vegetables, reduced production of glucose. In their paper ...

(HealthDay)For many people with diabetes, low blood sugar levels are a serious health risk, but researchers report that a new nasal powder quickly reverses the effects of this dangerous condition.

An inexpensive first-line treatment for type 2 diabetes may also reduce heart disease in those with type 1 diabetes, according to a new global trial led by the University of Glasgow.

In a landmark study, UNC School of Medicine researchers have shown that blood glucose testing does not offer a significant advantage in blood sugar control or quality of life for type 2 diabetes patients who are not treated ...

Low-income Hispanics with Type 2 diabetes who received health-related text messages every day for six months saw improvements in their blood sugar levels that equaled those resulting from some glucose-lowering medications, ...

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‘Lifting the cloud’ of diabetes with a special dog – Press Pubs

Posted: June 21, 2017 at 10:42 am

Since her diagnosis of Type 1 diabetes in 1989, Madyi Stangl has felt that the disease has placed a cloud on her life limiting her ability to travel and live life.

But that cloud has lifted for the Minneapolis resident, thanks to a special golden retriever named Willy.

Willy is a diabetes assistance dog that was given to Stangl by Can Do Canines, a New Hope-based nonprofit that trains dogs to help people who live with diabetes, autism, seizures, hearing loss and mobility issues.

Madyi and Willy graduated in a class of 14 on June 10.

Willy was named by Wilma Audrey Loken, who donated money to Can Do Canines. She died before Willy graduated, but her two daughters, their husbands and her son attended the graduation ceremony. One daughter, Beth Brostrom, and her husband are members of the White Bear Lions Club.

Willy can detect changes in Stangls blood sugar levels by scent. He alerts Madyi to high or low blood sugar levels by touching her with his paw. If she doesnt respond, he will whine or whimper and eventually do whatever he needs to do to get her attention. He is trained to bring glucose tablets or even a cell phone to Stangl.

Recently, Stangl had a scary low of 36 during the night. When she failed to respond to Willys touches, he laid over her body until she woke up, checked her blood sugar levels and ate food to bring her levels back up to normal.

Can Do Canines has produced nearly 600 teams of dogs and their human companions since opening in 1989, according to Sarah Schaff, client services coordinator.

The organization can give away the dogs, which are sold by other organizations for $20,000 or more, because of volunteers and many donors, Schaff says.

Funding comes from donations from individuals, companies and grants. Schaff reports that the organization does not receive any state or federal funds, relying solely on donations, fundraisers and bequests.

Puppies are bred in a cooperative program with other certified service dog organizations and raised by volunteers. Many receive their initial training in six Minnesota and two Wisconsin prisons.

Schaff notes that the prison environment is good for the dogs as well as the inmates.

It gives dogs a 24/7 taste of what life will be like when they are working, she says, adding that there are many studies pointing to the therapeutic benefits for the inmate handlers as well.

The organization has a screening process to find suitable candidates to match with dogs that are in the system or are in training.

It takes two years to raise and train a dog to be an assistance animal, Schaff said.

Madyi works as the operations lead for the University of Minnesota Physicians and Willy accompanies her to work. He alerted a diabetic co-worker of Stangl to a low blood sugar level.

Stangl grew up with dogs and reports that having Willy around is like having a big security blanket that I carry with me all the time. She is now more confident as well.

Even though Im going to continue on as this girl with this physical reminder of my disability, Im a little prouder because Im able to shed light on diabetes. Diabetes is an invisible illness, something that needs to be seen because its not something to be taken lightly, she said.

Even though Willy is a beautiful and friendly dog, Stangl asks that people refrain from touching him or any other assistance dog without permission of the owner.

When we are out in public and Willy is wearing his vest, its important not to make eye contact or distract him, Stangl says. He is working for me, and if he gets distracted, he stops working, and that could be dangerous.

Schaff says that Can Do Canines is in need of volunteers to raise and train Labrador, collie and poodle puppies for two years and return them to the company for further training. For more information, go to http://www.can-do-canines.org.

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ALS Research Forum | To Evaluate Stem Cell Therapies, Think … – ALS Research Forum

Posted: June 20, 2017 at 6:47 pm

Testing stem cell therapies unilaterally?A side-by-side comparison of strength of key muscles may enable scientists to evaluate stem cell therapies for the disease. The approach aims to control for the variability of the disease internally, without historical cohorts and/or the use of a placebo (see Donofrio and Bedlack, 2011; Glass et al., 2016).The biceps and triceps appear to be most reliable muscles to monitor progression in people with ALS according to this analysis (Rushton et al., 2017). [Neural progenitor cells. Courtesy of Nature Cell Biology. Reproduced with permission.]

Motor neurons degenerate in ALS. Why these cells are destroyed remains unclear. Therefore, how to slow or stop this destruction of motor neurons in ALS remains an open question.

In the meantime, a growing number of scientists are turning to stem cells in hopes to promote motor neuron survival in people with ALS and/or reduce their toxicity (see December 2015 conference news). But how to evaluate these strategies in the clinic remains hotly debated.

Now, a research team at Cedar Sinai Medical Center in Los Angeles, California reports that an emerging outcome measure, which involves monitoring muscle strength, may facilitate the evaluation of stem cell therapies for the disease (Rushton et al., 2017). The study, led by Clive Svendsen, found that functional decline of key muscles on the left and right side of people with ALS progressed at a similar rate. The results suggest that at least some stem cell therapies could be evaluated unilaterally by comparing the strength of muscles on the treated and untreated side for each of these muscle groups.

This side-by-side comparison, according to a subsequent power analysis, may enable clinicians to evaluate stem cell therapies for ALS in a smaller sample size without the need for sham surgeries and/or placebo injections.

This unilateral approach is emerging as an alternative to evaluate a growing number of potential neuroprotective strategies for neurodegenerative diseases including ALS (see NCT02943850, NCT02478450; Glass et al., 2016).

The study is published on June 9 in Neurology.

The retrospective analysis, performed in collaboration with Cedar Sinais Robert Baloh, studied the rates of decline of 6 upper and lower muscle groups in nearly 750 people with ALS determined by fixed dynamometry. These longitudinal datasets, previously collected by physical therapist Pat Andres and colleagues, now at Massachusetts General Hospital, capture the decline in strength of key muscles in people with ALS during at least a 16-month period measured by either the TUFTS Quantitative Neuromuscular Exam (TQNE) or more recently, the Accurate Test of Limb Isometric Strength (ATLIS) system (Andres et al., 1986; Shields et al., 1998; Andres et al., 2012.

Analyzing therapies by hand. Meanwhile, Biogen scientists in Cambridge, Massachusetts are turning to hand-held dynamometry to evaluate potential therapies for ALS. The emerging strength-based measure highly correlates with the progressive loss of motor function (ALS-FRS-R) and breathing capacity (FVC) according to a retrospective analysis of 924 people with ALS presented at the 2017 meeting of the American Academy of Neurology (see May 2017 news). And, according to a subsequent side-by-side comparison, these musclesdecline at similar rates. [Image: Douma et al., 2014 under CC BY 2.0 license.]

The study builds on previous work, led by Barrow Institutes Jeremy Shefner in Phoenix, Arizona and Biogens Toby Ferguson in Cambridge, Massachusetts, which found that monitoring the strength of key muscles using hand-held dynamometry is a reliable and reproducible approach to measure progression of ALS in a clinical setting and thereby, may facilitate the evaluation of potential therapies (see May 2017 conference news; Shefner et al., 2014).

Now, Svendsens team is gearing up to evaluate their potential stem cell therapy for ALS. The strategy uses genetically engineered neural progenitor cells (NPCs) to deliver GDNF into the CNS in hopes to protect motor neurons in people with the disease (see April 2017 news; Gowing et al., 2014). The approach is at the phase 1 stage. Stay tuned.

Featured Paper

RushtonDJ, Andres PL, Allred P, Baloh RH,SvendsenCN. Patients with ALS show highly correlated progression rates in left and right limb muscles. Neurology. 2017 Jun 9. [PubMed].

References

ShefnerJM, Liu D, Leitner ML, Schoenfeld D, Johns DR, Ferguson T, Cudkowicz M.Quantitativestrengthtesting in ALS clinical trials. Neurology. 2016 Aug 9;87(6):617-24. [PubMed].

Andres PL, Skerry LM, Munsat TL, Thornell BJ, Szymonifka J, Schoenfeld DA, Cudkowicz ME. Validation of a new strength measurement device for amyotrophic lateral sclerosis clinical trials. Muscle Nerve. 2012 Jan;45(1):81-5. [PubMed].

Andres PL, Hedlund W, Finison L, Conlon T, Felmus M, Munsat TL.Quantitative motor assessment in amyotrophic lateral sclerosis. Neurology. 1986 Jul;36(7):937-41.[PubMed].

Glass JD, Hertzberg VS, Boulis NM, Riley J, Federici T, Polak M, Bordeau J, Fournier C, Johe K, Hazel T, Cudkowicz M, Atassi N, Borges LF, Rutkove SB, Duell J, Patil PG, Goutman SA, Feldman EL. Transplantation of spinal cord-derived neural stem cells forALS: Analysis of phase 1 and 2 trials. Neurology. 2016 Jul 26;87(4):392-400.[PubMed].

Gowing G, Shelley B, Staggenborg K, Hurley A, Avalos P, Victoroff J, Latter J, Garcia L, Svendsen CN. Glial cell line-derived neurotrophic factor-secreting human neural progenitors show long-term survival, maturation into astrocytes, and no tumor formation following transplantation into the spinal cord of immunocompromised rats. Neuroreport.2014 Apr 16;25(6):367-72. [PubMed].

Further Reading

Atassi N, Beghi E, Blanquer M, Boulis NM, Cantello R, Caponnetto C, Chi A, Dunnett SB, Feldman EL, Vescovi A1, Mazzini L; attendees of the International Workshop on Progress in Stem Cells Research for ALS/MND. Intraspinal stem cell transplantation for amyotrophic lateral sclerosis: Ready for efficacy clinical trials? Cytotherapy.2016 Dec;18(12):1471-1475. [PubMed].

Donofrio PD, Bedlack R. Historical controls in ALS trials: a high seas rescue? Neurology. 2011 Sep 6;77(10):936-7. [PubMed].

clinical trial clinical trial design disease-als gdnf neuralstem neuroprotection stem cell topic-clinical topic-randd

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Brain Tumors: Still Devastating, but Treatment Has Come a Long Way – Newswise (press release)

Posted: June 20, 2017 at 6:46 pm

Newswise BIRMINGHAM, Ala. A brain tumor was the furthest thing from Kathy Englishs mind that day in 2003 when she walked into a neurologists office. Shed had some uncontrolled sinus issues, so her doctors had ordered a variety of tests, including an MRI. When she arrived to get the MRI results, the neurologist said he had not yet had a chance to look at them himself.

He said wed look at them together, English recalled. As he looked over the scan, he pointed out a small abnormality, a tumor which he described as a meningioma. Then he saw another one. And another. By this time, I was getting pretty worried. Ultimately, he found 12, and now I was really worried.

A meningioma is a usually benign, slow-growing tumor. While referred to as a brain tumor, it actually does not grow from brain tissue but rather from the meninges, layers of tissue which cover the brain. Still, 12 meningiomas are not to be taken lightly.

The neurologist immediately referred English to neurosurgeon James Markert, M.D., an internationally renowned brain tumor expert at the University of Alabama at Birmingham.

Markert, who is professor and chair of the Department of Neurosurgery in the UAB School of Medicine, says meningiomas are relatively rare, but certainly not unheard of. He followed English for several years, and when one of the tumors began to grow, he surgically removed it, along with eight others that were easily accessible. Two more were later eliminated through a gamma knife radiation procedure. Markert continues to monitor the others. Through it all, English never had any symptoms, other than a bucket-full of anxiety.

It was like knowing you have bugs on your head Get them off! Get them off! she said. Its so reassuring to know that Im being treated and monitored by some of the top brain tumor people in the nation.

Her experiences made English something of a brain tumor expert herself, certainly enough to realize something was not right when her husband, John, became dizzy and off-balance after bending over to unplug a computer cord. Hed had a couple of bad headaches in the previous weeks, and that evening in the fall of 2016, there was something obviously wrong.

We ruled out stroke pretty quickly, and our physician ordered an MRI, English said. The results came back astrocytoma. A brain tumor. We were stunned.

Two days later, John English was in Markerts office, and in less than two weeks, had surgery to remove a Grade 2 tumor. His recovery has been robust, and he knows he is lucky.

While we never anticipated having a second person in the family with a brain tumor, Kathys experiences made us proactive, John said. My prognosis is so much better due to the quick recognition of the tumor, and the quick response by UAB.

The Englishes did not consider themselves prime candidates for brain tumors. Both are pescatarians (individuals who add fish to a vegetarian diet) who stay fit and keep a close eye on their health.

The scientific community still has much to learn in order to predict the onset of a brain tumor or who is at risk, said Markert, who holds the James Garber Galbraith Endowed Chair of Neurosurgery at UAB and is a senior scientist in the Comprehensive Cancer Center. Some, called primary tumors, arise in the brain. Others are called metastatic tumors, which arise elsewhere in the body and migrate to the brain.

The good news, Markert says, is that the landscape for brain tumor therapy is much better now than ever before.

A diagnosis of a malignant brain tumor is still devastating, but weve come a long way, he said. The horizon is very bright for the development of even more impactful treatments in the very near future.

Markert credits improved imaging with some of that optimism. Improvements in neuroimaging can now reveal much more information about the makeup of tumors.

We used to classify tumors based simply on their microscopic appearance, Markert said. We are now able to look at mutations within tumor cells, and weve found that certain sets of mutations are associated with different tumor types and subtypes. This really is precision medicine, as we can now tailor therapy based on our better understanding of the genetic signature of an individual tumor.

A new oral chemotherapy agent called temozolomide is a good example. It is effective on some tumors, but others are resistant to the drug. Advances in genetic testing can predict which patients will respond best to the drug and which will not.

Another new agent, aminolevulinic acid, or 5-ALA, is used in a fluorescence imaging technique. The drug is absorbed into tumors and causes them to glow when viewed on an MRI. Surgeons can then better visualize the tumor, especially at its boundaries with healthy cells. Those boundaries are usually indistinct, and the line between tumor and healthy tissue can be blurred. 5-ALA helps guide surgeons as they attempt to remove as much of a tumor as possible while leaving healthy tissue intact. 5-ALA is expected to be approved for use by the FDA in the near future.

New technology will soon be in place at UAB, such as intraoperative MRI scanning, where surgeons will have the ability to do real-time MRI scans in the operating room during surgery. Another advance, also based on improved MRI use, will employ lasers surgically inserted into the tumor to precisely destroy tumor cells with heat energy.

Markert says proton therapy, an option over traditional radiation technology and coming to UAB in 2019, can be a valuable tool for pediatric tumors or tumors situated close to delicate structures such as the brain stem or optic nerve.

Another promising therapy has been under investigation in Markerts lab for years. In 2001, Markert and his colleagues published initial results of a first-generation genetically engineered herpes virus as a therapy to destroy brain tumors. A second generation virus, known as M032, is currently undergoing clinical trials. The virus infects tumor cells and replicates, while leaving healthy cells alone.

The act of viral replication in the tumor kills the infected tumor cells and causes the tumor cell to act as a factory to produce new viruses. As the tumor cell dies, progeny viruses are released from the cell. These viruses infect other tumor cells in the vicinity and continue the process of tumor killing. The virus also causes the patients own immune system to attack the tumor.

This process, especially combined with advances in immunotherapy, presents a very promising approach to treating tumors, Markert said.

Markert explains that the bodys immune system is designed to patrol for foreign cells in the body, including mutated cancer cells. The immune systems killer T cells have an off-switch, known as a checkpoint. The checkpoint is usually turned off, keeping T cells from attacking healthy cells. It turns on again, usually in the presence of a foreign cell, prompting T cells to attack. But tumor cells are very good at fooling the checkpoint so it remains in the off position. Drugs known as checkpoint inhibitors are under development which would turn the checkpoint on, stimulating the T cells to attack the tumor.

One approach we are considering now is a combination of viral and immunotherapy, Markert said. The viral therapy using our modified herpes virus should produce a vibrant immune response, followed by introduction of the checkpoint inhibitors, which would turn on the checkpoints and activate individual T cells.

Markert is excited about the future of brain tumor research and treatment. As a leading academic medical center home of one of the nations Comprehensive Cancer Centers, and the states leader in personalized medicine, UAB is primed to be at the forefront of new discovery.

We have a remarkable array of talent here, in radiation oncology, hematology/oncology, neurology, neurosurgery, and other fields, he said. We have an outstanding research enterprise in both adult and pediatric brain tumors. Its an exciting time to be in this field.

Brain cancer is not the most prevalent kind of cancer breast and lung cancer top the list; but malignant brain tumors can be particularly devastating. The National Cancer Institute predicts 33,800 new cases in 2017. The NCI also estimates that 16,700 Americans will die of brain cancer this year.

We are turning a corner, but there are still too many people who die from brain tumors each year, Markert said. These patients and their families are very courageous people. We owe it to them to find better treatments.

The Englishes had two firsthand experiences to convince them to continue to be proactive and involved in their health care.

Pay attention to your body, and if something unusual happens, dont blow it off, John said. Be aggressive in following up. We are two people who paid attention to our medical issues and, as a result, got the right care to provide us the best possible outcomes.

About UAB

Known for its innovative and interdisciplinary approach to education at both the graduate and undergraduate levels, the University of Alabama at Birmingham is the state of Alabamas largest employer and an internationally renowned research university and academic medical center; its professional schools and specialty patient-care programs are consistently ranked among the nations top 50. UABs Center for Clinical and Translational Science is advancing innovative discoveries for better health as a two-time recipient of the prestigious Center for Translational Science Award. Find more information at http://www.uab.edu and http://www.uabmedicine.org.

EDITORS NOTE: The University of Alabama at Birmingham is a separate, independent institution from the University of Alabama, which is located in Tuscaloosa. Please use University of Alabama at Birmingham on first reference and UAB on subsequent references.

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Brain Tumors: Still Devastating, but Treatment Has Come a Long Way - Newswise (press release)

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