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A Molecular Revolution Is Underway in Thoracic Oncology – OncLive

Posted: June 22, 2022 at 2:01 am

Targetable alterations including BRAF V600E, EGFR exon 20 insertions, KRAS G12C mutations, MET exon 14 alterations, NTRK and RET rearrangements have taken up recent focus for investigators as data are pushing novel agents through the regulatory processes.

The fruits of decades of investigative efforts in thoracic oncology are ripe for picking, according to Solange Peters, MD, PhD. Targetable alterations including BRAF V600E, EGFR exon 20 insertions, KRAS G12C mutations, MET exon 14 alterations, NTRK and RET rearrangements have taken up recent focus for investigators as data are pushing novel agents through the regulatory processes. However, there are several hurdles preventing the translation of these agents into practice including the integration of standardized molecular testing.1,2

In addition to novel therapies illuminating new treatment paths for patients, the success of immunotherapeutic regimens in the metastatic disease has driven investigators to evaluate the applications of the regimens in early-stage resectable disease.3,4

As the trends move more toward targeted therapies [and we have] agents that are being integrated preresection and postresection, some of the barriers [we need to address are the] issues regarding molecular testing and really integrating that into practice, especially for these patients with early-stage disease, Peters said in an interview with OncologyLive. Immunotherapy also has a large role to play early disease with surgery or any kind of radical treatment. Thats really a revolution.

As a young investigator, Peters got her start in infectious disease research focusing the topic of her PhD at the Microbiology Institute at the University of Lausanne in Switzerland on the mechanisms of resistance for HIV infection. If you think about HIV infection and the first treatment, we were [investigating] the clonal divergence of HIV viruses creating resistance. And if you think about my wording it reminds you of cancer, right? How [do we] address something which might kill [an individual] taking into consideration genetic changes over time. As advances in HIV research plateaued, Peters looked for a way to translate her interest in genetic research to a new field.

I was working in HIV as a biologist and an MD and, at the time, HIV [infection] was almost under control, I was looking for a field where in the sensitivity of first disease, a second grows, where there is an unmet need in bridging medicine and biology, but also bridging genetics and genetic modifications with treatments. There is no better discipline than oncology, Peters said. I immediately found there what I loved in HIV. Its amazing how [rapidly] the discoveries are now coming, [in particular] looking at genetics.

Peters has earned a place of prominence among lung cancer investigators and in the oncology area as a whole. She is serving her second year as president of the European Society for Medical Oncology (ESMO). Additionally, Peters is chief of the Medical Oncology Service, an associate professor and chair of Thoracic Oncology, and the chief resident of thoracic malignancies in the Oncology Department at the University Hospital of Lausanne (CHUV) in Switzerland.

Peters is also an active participant in many scientific meetings, including the upcoming 23rd Annual International Lung Cancer Congress taking place July 28-30, 2022, in Huntington Beach, California. The program, hosted by Physicians Education Resource (PER), LLC, will cover a wide range of topics in thoracic oncology including updates on biomarkers, surgical treatment modalities for resectable disease, and more (Sidebar).

I want to know what my colleagues think about the [available] data, Peters said. I learn something about the nuance of the data, or the limitations, or maybe something I havent thought about. The Congress [agenda] is broad, so you do the same exercise [as in other meetings], but in a very comprehensive fashion and this is of tremendous importance.

Lung cancer had beginnings in a category of diseases associated with very poor outcomes, Peters noted. Using the traditional surgery, chemotherapy, and radiation, the outcomes for [patients with] lung cancer have been very, very disappointing for years. However, as data began to read out from several landmark trials, Peters said that a new story began to unfold in the field in 2 important chapters for thoracic malignancies.

The first chapter is molecular biology, Peters said. Were trying to understand and discover what are the oncogenes leading to the malignant phenotype. [This research] has led to a wonderful portfolio of targeted therapies.

This course of molecular discovery kicked off when investigators identified the role of EGFR mutations in nonsmall cell lung cancer (NSCLC) leading to the introduction of personalized medicine in the field, specifically with the EGFR inhibitor gefitinib (Iressa).2

In the following decade, progress to uncover aggressive mutations accelerated with the identification of 15 mutations that afford patients opportunities for therapy beyond chemotherapy and radiation.

For example, in the past 2 years, treatment options for metastatic NSCLC have risen exponentially with agents including mobocertinib (Exkivity) and amivantamab-vmjw (Rybrevant) for patients with EGFR exon 20 insertions, tepotinib (Tepmetko) and capmatinib (Tabrecta) for patients with MET exon 14 skipping mutations, sotorasib (Lumakras) for patients with KRAS G12C mutations, and lorlatinib (Lorbrena) for patients with ALK-positive disease.5

From time to time we will discover new compounds or new targets, Peters said. I think the low hanging fruits might have been caught by in terms of oncogenes. Although progress has not stalled in discovery, Peters noted that the focus is now shifting toward improvements in the pharmacology of the agents being developed. We have been handling more potent drugs, broader drugs in terms of preventing resistance, and very often drugs [developed for metastatic disease], which with lung cancer [can] spread over everywhere in the body, including the brain.

Peters noted that faced with all progress in molecularly defined disease, testing rates across countries creates limitations in identifying appropriate patients for select therapies. In Switzerland, [for example], we are very well served, I would say that today every patient with lung cancer can be tapped for the genetic alterations, Peters said of her home country. This is not the case elsewhere. Unfortunately, if you look at the picture of molecular testing in Europe, less than half of patients can get access to a decent testing. Thats probably where most advances are needed because it creates unacceptable inequities in the cancer journey.

For lung cancer specialists, the plethora of actionable mutations has exploded over the past decade. Most recently, advances in the breast cancer space has opened new options for patients with lung cancer with HER2 amplification.

This new journey lung cancer specialists are on is because of [discoveries in] breast cancer, Peters said. In lung cancer, the development of HER2-targeted therapies required looking at the disease in a different light. We discovered that [in lung cancer] we dont speak about the same HER2 alteration, Peters said. We call amplification, which translates into an overexpression, the quantity. Its really a modification of the protein.

Early efforts to identify therapies for patients with HER2-mutant diseasewhich accounts for approximately 2% of all NSCLC casesfound that translation of select agents deemed successful in breast cancer did not afford the same risk/benefit ratio for patients with lung cancer.6 For example, 18 patients treated ado-trastuzumab emtansine (T-DM1; Kadcyla) in a phase 2 basket trial (NCT02675829) showed that among the overall response rate (ORR) was 44% (95% CI, 22%-69%) with a median progression-free survival (PFS) of 5 months (95% CI, 3.0-9.0).7

We tried all of these drugs [that were successful in breast cancer], as well as afatinib [Gilotrif], which is a pan-HER inhibitor, in lung cancer, [for patients with] exon 20 insertions, Peters said. These compounds have given rise to small activity, [but] if you try to [determine the] risk/ benefit assessment, none of them have really reached the bar which you would consider standard of care.

However, data from a trial investigating the use of fam-trastuzumab deruxtecan-nxki (Enhertu) has resulted in a breakthrough for patients with HER2-mutant disease, regardless of mutation site.6,8 Data from the DESTINY-Lung01 trial (NCT03505710), which evaluated a total of 91 patients with HER2-mutant NSCLC, demonstrated that the antibody-drug conjugate elicited an objective response rate of 55% (95% CI, 44%-65%), the median duration of which was 9.3 months (95% CI, 5.7-14.7) (Table). Further, the median PFS was 8.2 months (95% CI, 6.0-11.9), and the median overall survival was 17.8 months (95% CI, 13.8-22.1).8

I wouldnt say there were no options but there was no standard option in HER2-mutant NSCLC, Peters said. Suddenly this new generation antibody-drug conjugates have given rise to wonderful results in breast cancer [and now in] lung cancer, where suddenly you reach a threshold where probably with close to 60% response rate. We have gone through these limitations, and we [now] have an option.

The FDA has accepted for priority review a supplemental biologics license application for trastuzumab deruxtecan for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have a HER2 mutation and who have received a prior systemic therapy.9

The application is supported by findings from the phase 2 DESTINY-Lung01 as well as data from the phase 1 DS8201-A-J101 trial (NCT02564900). In the phase 1 study, trastuzumab deruxtecan led to an overall response rate (ORR) of 72.7% (n = 8) among 11 patients with HER2-mutant NSCLC.10 The median PFS in these patients was 11.3 months (95% CI, 8.1-14.3).

Regarding the agents safety profile, the adverse effects (AEs) observed with trastuzumab deruxtecan in DESTINY-Lung01 were comparable with those reported in prior clinical trials.

The most common grade 3 or higher drug- related, treatment-emergent AEs included neutropenia (18.7%), anemia (9.9%), nausea (8.8%), fatigue (6.6%), leukopenia (4.4%), diarrhea (3.3%), and vomiting (3.3%).9

Twenty-three patients (25%) discontinued treatment because of drug-related, treatment-emergent AEs. Of note, 26% of patients had interstitial lung disease (ILD) or pneumonitis related to treatment per assessment by an independent committee. The majority of ILD events (75%) were low grade (grade 1, 12.5%; grade 2, 62.5%). Additionally, 4 grade 3 (4.4%) and 2 grade 5 (2.2%) ILD or pneumonitis events were reported.

The second chapter of the lung cancer revolution is one that Peters refers to as exciting: immunotherapy. Immunotherapy has led to long term survival for some patients in lung cancer despite [having] metastatic disease, Peters said. When I started oncology, one could not conceive that the patient with metastatic [disease] would survive years. We now have very strong data showing that immunotherapy should be used alone or in combination in nearly all metastatic patients.

Peters noted that the refinement of strategies with immunotherapy is an area that will take investigators into the next wave of clinical advances. Immunotherapies are now moving into early disease. When I say early these are [patients with] small nodules that are resected. These approaches are about combining [immunotherapy] with surgery and curative intent treatments. How can you make surgery more efficient in creating cure?

Data for patients with early-stage disease have generated excitement including data from the phase 3 CheckMate 816 trial (NCT02998528). Investigators compared nivolumab (Opdivo) plus chemotherapy with chemotherapy alone for treatment of patients with resectable NSCLC.11 The median eventfree survival (EFS) was 31.6 months in the nivolumab plus chemotherapy arm vs 20.8 months in the control arm (HR, 0.63; 97.38%, 0.43-0.91). The 1-year EFS rate was 76% in the experimental arm and 63% in the control; the 2-year EFS was 64% vs 45%, respectively.11

These data supported the approval of the combination, making it the first approval for patients in the neoadjuvant setting for patients with NSCLC in March 2022.12

In terms of adjuvant therapy for earlystage disease, data from the IMpower010 study, supported the approval of atezolizumab (Tecentriq) for patients with stage II-IIIA NSCLC whose tumors have PD-L1 expression of at least 1%.13

The primary end point was disease-free survival (DFS). Among patients who received atezolizumab the median DFS was not reached (95% CI, 36.1-not estimable [NE]) vs 35.3 months (95% CI, 29.0-NE) with best supportive care (HR, 0.66; 95% CI, 0.50-0.88; P = .004).

Investigators also assessed patients with PD-L1 expression of at least 50%, among whom the DFS benefit was more pronounced with atezolizumab compared with best supportive care (HR, 0.43; 95% CI, 0.27-0.68). However, an exploratory subgroup analysis of patients with PD-L1 expression 1%-49% the DFS benefit was less pronounced (HR 0.87; 95% CI, 0.60-1.26).

We are seeing the first data from these trials already, Peters said, noting that the road for determining optimal treatment strategies for patients is a long one. In the [next several] years there will be way more trials in early disease, Peters said.

Peters remains hopeful about the future of the space, as it moves toward integration of molecular testing strategies and opening up new and potentially curable avenues for patients with thoracic cancers. Within that pipeline she noted that prevention strategies that may shift the curve in terms of disease incidence.

We need to do more screening for lung cancer and we need to start to implement programs for heavy smokers, [which incorporate] regular CT scans, Peters said adding that with these efforts to improve the identification of early-stage disease coupled with improvements in the landscape would be a step toward curable disease.

I think what is really for us, something which really makes us feel differently as being lung cancer clinic and, is this new [direction of the] fieldtrying to cure more patients, Peters said. Thats maybe what differentiates us a lot from breast cancer specialists. When breast cancer specialists treat with chemotherapy and hormonal therapy, as well as surgery, they get to cure individuals, the [survival] curves in breast cancer can be very, very high between 80% and 100%. In lung cancer, when you perform surgery, and maybe [administer] chemotherapy for patients, only half of the patients will be cured, or even less, maybe 40%. Even with all the lung specialists, we still [making efforts to] cure the disease.

On a more personal note, Peters said that although being on the ground floor of breakthrough research are moments in a career that standout, her attention is now on the future successes of her fellows and mentees. My proudest moments now are to have one of my young fellows or mentees being recognized for something he or she has done, Peters said.

She noted that in preparing the next generation of investigators mentorship is of the utmost importance. I was carried by wonderful mentors, Peters said. A mentor is someone who will put you on the scene, give your name to give a talk.

In addition to promoting early and lasting relationships among physician scientists, Peters said that promoting the interprofessional dimension of cancer care is one of the items that she placed a focus on as the president of ESMO. The medical oncologist cannot work alone, everything has become multiprofessionalmolecular pathologists, the surgeons the radiologists, and so onwe need to understand that these data have to go through all these layers [to convey information.

Broadening the scope of conveying information, Peters spearheaded the creation of the International Cancer Foundation (ICF) at ESMO.14 The ICF aims to provide educational activities to clinicians in areas that are underserved, opening the expansion of knowledge of advances in cancer to the world.

Were doing the same thing we do in ESMO, but translating into a visibility concept, which can be also used in Africa, in South and Central America, and in all countries of India, for example, Peters said. We realized that ESMO is in a position to reach out to them and address their specific needs and concerns. The ICF aims to support, financially and practically, activities that enhance cancer prevention, diagnosis, treatment and follow-up where they are most needed. If we can give a little bit of our energy to help the [clinicians who may be] a little bit delayed in receiving these data], it would be a good move.

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A bit of coffee is okay during pregnancy – Futurity: Research News

Posted: June 22, 2022 at 2:01 am

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Enjoying a bit of coffee causes no increased risk to pregnancy, researchers report.

The researchers used genetics to analyze coffee drinking behavior, and their findings show limited coffee consumption during pregnancy didnt increase the risk of miscarriage, stillbirth, or premature birth.

Current World Health Organization guidelines say pregnant women should drink less than 300mg of caffeine, or two to three cups per day, says Gunn-Helen Moen of the Institute for Molecular Bioscience at the University of Queensland. But thats based on observational studies where its difficult to separate coffee drinking from other risk factors like smoking, alcohol, or poor diet.

We wanted to find out if coffee alone really does increase the risk of adverse pregnancy outcomes, and the research shows this isnt the case.

Coffee drinking behavior is partly due to genetics, with a specific set of genetic variants affecting how much coffee we drink, says Daniel Hwang of the Institute for Molecular Bioscience.

We showed that these genetic variants not only affect coffee consumption in the general population but also in pregnant women.

For the study in the International Journal of Epidemiology, the researchers used a method called Mendelian randomization which uses eight genetic variants that predict pregnant womens coffee drinking behavior and examined whether these variants were also associated with birth outcomes.

Because we cant ask women to drink prescribed amounts of coffee during their pregnancy, we used genetic analyses to mimic a randomized control trial, Hwang says.

The genetic analysis found there was no greater risk of miscarriage, stillbirth, or premature birth for women who drank coffee.

When it comes to diet during pregnancy women are often advised to cut things out, but this study shows they can still enjoy coffee without worrying about increasing the risk of these pregnancy outcomes, Hwang says.

The researchers emphasize the study only looked at certain adverse pregnancy outcomes, and it is possible caffeine consumption could affect other important aspects of fetal development.

For that reason, we dont recommend a high intake during pregnancy, but a low or moderate consumption of coffee, Moen says.

Researchers used genetic data from the Coffee and Caffeine Genetics Consortium, the UK BioBank, the Avon Longitudinal Study of Parents and Children, and 23andMe.

Source: University of Queensland

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Bionano Genomics Announces a Publication From the First Affiliated Hospital of Zhengzhou Highlighting the Utility of OGM – GuruFocus.com

Posted: June 22, 2022 at 2:01 am

SAN DIEGO, May 12, 2022 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. ( BNGO), pioneer of optical genome mapping (OGM) solutions on the Saphyr system and provider of NxClinical software, the leading solution for visualization, interpretation and reporting of genomic data, today announced the publication of an evaluation of OGM from The First Affiliated Hospital of Zhengzhou, the largest hospital in Central China, highlighting the utility of OGM for structural variant analysis, including in a workflow for preimplantation genetic testing.

In this study, researchers, led by Dr. Xiangdong Kong, evaluated the use of OGM to detect chromosome balanced translocations and compared results to a variety of methods, including karyotype analysis, FISH, and CNV-seq. Balanced reciprocal translocations are one of the most common chromosomal abnormalities and may lead to infertility, recurrent pregnancy loss, or genetic defects. Analysis of this abnormality may be helpful in the screening and analysis of embryos prior to implantation, as part of fertility treatment. The paper suggests a need for new methods to complement existing analysis techniques, such as karyotype and FISH, which are described as time consuming and relatively low-resolution, and next generation sequencing (NGS) which can enable copy number variation (CNV) analyses at the whole genome level but cannot be used to detect chromosomal translocations or inversions. The authors demonstrated that OGM performed well in the analysis of these variants, which led them to suggest that OGM could be used as part of the workflow to detect chromosomal abnormalities at a higher resolution.

We believe this paper highlights the growing validation of OGM in different applications for clinical research in cytogenetics. The work by Dr. Kong and his team at Zhengzhou University further extends this validation and highlights the utility of OGM. Incorporating OGM data in the analysis of embryos prior to implantation is innovative and the approach could be part of a solution for recurrent pregnancy loss, which represents an area of unmet need globally, commented Erik Holmlin, PhD, president and chief executive officer of Bionano Genomics.

The paper is available at:

Evaluation of optical genome mapping for detecting chromosomal translocation in clinical cytogenetics - Dai - - Molecular Genetics & Genomic Medicine - Wiley Online Library

About Bionano Genomics

Bionano Genomics is a provider of genome analysis solutions that can enable researchers and clinicians to reveal answers to challenging questions in biology and medicine. The Companys mission is to transform the way the world sees the genome through OGM solutions, diagnostic services and software. The Company offers OGM solutions for applications across basic, translational and clinical research. Through its Lineagen business, the Company also provides diagnostic testing for patients with clinical presentations consistent with autism spectrum disorder and other neurodevelopmental disabilities. Through its BioDiscovery business, the Company also offers an industry-leading, platform-agnostic software solution, which integrates next-generation sequencing and microarray data designed to provide analysis, visualization, interpretation and reporting of copy number variants, single-nucleotide variants and absence of heterozygosity across the genome in one consolidated view. For more information, visit http://www.bionanogenomics.com, http://www.lineagen.com or http://www.biodiscovery.com

Forward-Looking Statements of Bionano Genomics

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as may, will, could, suggest, and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, the ability and utility of OGM and the Saphyr system to detect chromosome balanced translocations in preimplantation embryos and the potential for OGM to become part of workflow analyses to detect chromosomal abnormalities. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the impact of the COVID-19 pandemic on our business and the global economy; general market conditions; changes in the competitive landscape and the introduction of competitive technologies or improvements in existing technologies; failure of future study results to support those demonstrated in the paper referenced in this press release; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts; the ability of medical and research institutions to obtain funding to support adoption or continued use of our technologies; and the risks and uncertainties associated with our business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2021 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on managements assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

CONTACTSCompany Contact:Erik Holmlin, CEOBionano Genomics, Inc.+1 (858) 888-7610[emailprotected]

Investor Relations:Amy ConradJuniper Point+1 (858) 366-3243[emailprotected]per-point.com

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Connection Map Reveals Changes in the Injured Brain – Technology Networks

Posted: June 22, 2022 at 1:59 am

Scientists from the University of California, Irvine have discovered that an injury to one part of the brain changes the connections between nerve cells across the entire brain. The new research was published this week inNature Communications.

Every year in the United States, nearly two million Americans sustain a traumatic brain injury (TBI). Survivors can live with lifelong physical, cognitive and emotional disabilities. Currently, there are no treatments.

One of the biggest challenges for neuroscientists has been to fully understand how a TBI alters the cross-talk between different cells and brain regions.

In the new study, researchers improved upon a process called iDISCO, which uses solvents to make biological samples transparent. The process leaves behind a fully intact brain that can be illuminated with lasers and imaged in 3D with specialized microscopes.

With the enhanced brain clearing processes, the UCI team mapped neural connections throughout the entire brain. The researchers focused on connections to inhibitory neurons, because these neurons are extremely vulnerable to dying after a brain injury. The team first looked at the hippocampus, a brain region responsible for learning and memory. Then, they investigated the prefrontal cortex, a brain region that works together with hippocampus. In both cases, the imaging showed that inhibitory neurons gain many more connections from neighboring nerve cells after TBI, but they become disconnected from the rest of the brain.

Weve known for a long time that the communication between different brain cells can change very dramatically after an injury, saidRobert Hunt, PhD, associate professor ofanatomy and neurobiologyand director of theEpilepsy Research Centerat UCI School of Medicine whose lab conducted the study, But, we havent been able to see what happens in the whole brain until now.

To get a closer look at the damaged brain connections, Hunt and his team devised a technique for reversing the clearing procedure and probing the brain with traditional anatomical approaches.

The findings surprisingly showed that the long projections of distant nerve cells were still present in the damaged brain, but they no longer formed connections with inhibitory neurons.

It looks like the entire brain is being carefully rewired to accommodate for the damage, regardless of whether there was direct injury to the region or not, explained Alexa Tierno, a graduate student and co-first author of the study. But different parts of the brain probably arent working together quite as well as they did before the injury.

The researchers then wanted to determine if it was possible for inhibitory neurons to be reconnected with distant brain regions. To find out, Hunt and his team transplanted new interneurons into the damaged hippocampus and mapped their connections, based on the teamsearlier researchdemonstrating interneuron transplantation can improve memory and stop seizures in mice with TBI.

The new neurons received appropriate connections from all over the brain. While this may mean it could be possible to entice the injured brain to repair these lost connections on its own, Hunt said learning how transplanted interneurons integrate into damaged brain circuits is essential for any future attempt to use these cells for brain repair.

Our study is a very important addition to our understanding of how inhibitory progenitors can one day be used therapeutically for the treatment of TBI, epilepsy or other brain disorders, said Hunt. Some people have proposed interneuron transplantation might rejuvenate the brain by releasing unknown substances to boost innate regenerative capacity, but were finding the new neurons are really being hard wired into the brain.

Hunt hopes to eventually develop cell therapy for people with TBI and epilepsy. The UCI team is now repeating the experiments using inhibitory neurons produced from human stem cells.

This work takes us one step closer to a future cell-based therapy for people, Hunt said, Understanding the kinds of plasticity that exists after an injury will help us rebuild the injured brain with a very high degree of precision. However, it is very important that we proceed step wise toward this goal, and that takes time.

Reference:Frankowski JC, Tierno A, Pavani S, Cao Q, Lyon DC, Hunt RF. Brain-wide reconstruction of inhibitory circuits after traumatic brain injury. Nat Commun. 2022;13(1):3417. doi:10.1038/s41467-022-31072-2

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Scientists Used CRISPR to Trace Every Human Gene to Its Function – Singularity Hub

Posted: June 22, 2022 at 1:59 am

Genes are like Egyptian hieroglyphs. Thanks to advances in whole-genome sequencing, its increasingly easy to read each DNA letter. But the strings of A, T, C, and G bring up a second puzzle: what, if anything, do they mean?

Its a problem that has haunted biologists since the completion of the Human Genome Project. By tapping into our genetic base code, the project assumed, wed be able to master control of inherited diseases, edit them at will, and easily predict the consequences of any gene that laid the foundation for our bodies, functions, and lives.

The vision didnt exactly work out. DNA sequences, while capturing extremely powerful genetic information, dont necessarily translate to indicating how our bodies behave. Genes can turn on or off in different tissues depending on the cells need. Reading a DNA sequence for any gene is like parsing the base code of a cells internal program. Theres the raw genetic codethe genotypewhich determines the phenotype, lifes software that controls how cells behave. Linking the two has taken decades of painstaking experiments, slowly building up an encyclopedia of knowledge that decodes the influence of a gene on biological functions.

A new study ramped up the effort. Led by Drs. Thomas Norman and Jonathan Weissman at Memorial Sloan Kettering Cancer Center in New York and the University of California, San Francisco, respectively, the team built a Rosetta Stone for translating genotypes to phenotypes, with the help of CRISPR.

They went big. Changing gene expression in over 2.5 million human cells, the tech, dubbed Perturb-seq, comprehensively mapped how each genetic perturbation alters the cell. The technology centers around a sort of CRISPR on steroids. Once introduced into cells, Perturb-seq rapidly changes thousands of genesa brutal shakeup at the genomic scale to see how single cells respond.

In other words, Perturb-seq is a large-scale tool that can help scientists translate DNA code to functiona Rosetta Stone for uncovering our cells inner workings. Years in the making, the dataset is open for anyone to explore.

I think this dataset is going to enable all sorts of analyses that we havent even thought up yet by people who come from other parts of biology, and suddenly they just have this available to draw on, saidNorman.

Whats the function of a gene? Its easy to think that genes are your destiny but thats far from the truth. Environmental factors, such as a massive bowl of spaghetti or a walk along the beach, can easily change gene expression, bodily functions, and potentially your body and mind.

If thats the case, whats the point of sequencing whole genomes if the outcome is always in flux? A central goal of genetics is to define the relationships between genotype and phenotype, the authors said. In other words, what does any gene actually do?

Scientists have long sought to build a bridge between genotype and phenotype. Its a painstaking process. One method, for example, perturbs genes that may be related to a disorder one by one and observes the cells behavior. Dubbed forward genetics, the idea is gene-focused rather than focusing on the phenotype. An alternative approach, reverse genetics, dives deep into how a body or mind changes with a specific genetic edit.

Each method is an uphill struggle. With over 20,000 genes in our bodies and every cell behaving slightly differently (even with the same genetic changes), deciphering a genes function often takes years, if not decades.

Is there any way to speed the process up?

Enter CRISPR. Long revered as a genetic editing multitool, the method has further blossomed into a biological translator. At its heart is a technology dubbed Perturb-seq, first published in 2016 to dissect the expression of genes. Perturb-seq makes it possible to follow the consequences of turning a gene on or off in a single cell. The method rapidly rose to fame in 2020 for its efficiency at altering multiple genes at once.

Its a huge win for cell biology, said the team. While scientists have readily chipped away at the massive web connecting genes and proteins, nailing down the role of individual genes has been a struggle. We often take all the cells where gene X is knocked down and average them together to look at how they changed, said Weissman. But sometimes when you knock down a gene, different cells that are losing that same gene behave differently, and that behavior may be missed by the average.

The idea behind Perturb-seq is pretty simple. Imagine a toddler breaking stuff and realizing what hes done after seeing the consequences. Perturb-seq uses CRISPR-Cas9 to silence multiple genes at once, which may sometimes change a cells behavior. While powerful, the tool has been hard to scale, studying at most a few hundred genetic perturbations at once for pre-defined biological questions.

So why not expand the method to the whole genome?

The advantage of Perturb-seq is it lets you get a big dataset in an unbiased way, said Norman. No one knows entirely what the limits are of what you can get out of that kind of dataset. Now, the question is, what do you actually do with it?

In the new study, the team first found the magic sauce for making genome-wide changes in human cells with CRISPR. A major point was to optimize a library of guide RNAs (sgRNAs), the bloodhounds that track down a gene. Next, they captured cells infected with CRISPR and analyzed their gene expression. Overall, the team focused on nearly 2,000 genes. Cross-referencing changed genes with each cells phenotype, they then clustered genes into networks that linked to a cellular outcome.

One enigmatic gene stood out: C7orf26. Nixing it with CRISPR changed how a cell builds a huge molecular complex, dubbed the Integrator, which helps make molecules that control gene activity. Before Perturb-seq, C7orf26 had never been associated with the complex before.

In another analysis, the team found a subset of genes that changes how daughter cells inherit the parent genome. For example, removing some genes altered the distribution of chromosomes as a cell divides. Adding or removing a chromosome can fundamentally change our biology, such as by leading to Down Syndrome.

To Norman, this aspect is the most interesting part of Perturb-seq. It captures a phenotype that you can only get using a single-cell readout. You cant go after it any other way.

This database is just the start. The team is looking to use Perturb-seq on other human cell types, and all the data is available for collaboration. With the rise of Ultima Genomics, an ultra-low-cost genomic sequencing solution, single-cell CRISPR screens are likely to play an even bigger role in biotechnology, such as in analyzing the genomes of iPSCs (induced pluripotent stem cells).

To Weissman, it may even spark a shift in how we approach cellular mysteries. Rather than defining ahead of time what biology youre going to be looking at, you have this map of the genotype-phenotype relationships, and you can go in and screen the database without having to do any experiments, he said.

Image Credit: Jen Cook/Chrysos Whitehead Institute

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Maike Sander named to lead the Max Delbrck Center – EurekAlert

Posted: June 22, 2022 at 1:59 am

image:Maike Sander has been selected to direct the Max Delbrck Center for Molecular Medicine (MDC). view more

Credit: Peter Himsel / MDC

On November 1, 2022, Prof. Maike Sander will take the reins as Scientific Director and Chair of the Board of the Max Delbrck Center for Molecular Medicine in the Helmholtz Association (MDC). The Supervisory Board of the MDC formally appointed her to the post on Thursday, June 16, 2022. The MDC, which is celebrating its 30th anniversary this year, is one of five Health Centers in the Helmholtz Association of German Research Centers. The internationally renowned researcher and experienced science manager Maike Sander will be succeeding Prof. Thomas Sommer, who has directed the MDC on an interim basis since 2019. That will make Sander the first woman to head one of the Helmholtz Health Centers.

The MDC has distinguished itself as an internationally renowned center for highly innovative biomedical research, says Maike Sander. Work at the MDC lays the foundation for better medicine of the future. The MDC provides on outstanding environment for research and attracts talent from around the globe. I had the opportunity to experience this first-hand as a visiting professor at the MDC. As Scientific Director, my goal will be to further strengthen the MDCs role as a leading biomedical research center and to deepen partnerships with other institutions in Berlin and beyond, so that our discoveries can be rapidly turned into medical innovations. Sander emphasizes that medical innovation needs strong basic science, clinical science and industry partners components that are all part of the vibrant Berlin biomedical ecosystem, she points out. The Berlin region is developing into a flourishing biotech pharma hub and I see the MDC as a principal driver of innovation in this landscape. I very much look forward to working with all stakeholders across Berlin.

Maike Sanders research focuses on identifying novel therapeutic approaches for diabetes. To this end, Sander studies the molecular mechanisms that underlie the formation and function of the different cell types in the pancreas, in particular the insulin-producing beta cells. Her goal is to identify strategies for replacing beta cells in diabetes using beta cells derived from human pluripotent stem cells.

Since 2012, Sander has served as the Director of the Pediatric Diabetes Research Center at the University of California, San Diego (UC San Diego), where she is also a Professor in the Departments of Pediatrics and Cellular & Molecular Medicine. In Berlin, Maike Sander will be appointed as Professor at the Charit Universittsmedizin.

Maike Sander is an outstanding scientist with a track record of innovation in biomedical research, says Bettina Stark-Watzinger, Germanys Federal Minister of Education and Research. I am delighted we have been able to bring her back to Germany after many years in the United States and to win her as the new Scientific Director of the Max Delbrck Center. It demonstrates the attractiveness of Berlin as a hub for biomedical research. As a scientist and administrator, Prof. Sander is the perfect match for the MDC with its mission to improve human health through transformative biomedical research. Also, having a female leader is an important signal. Prof. Sanders appointment represents a significant gain for German research.

Berlins Senator for Higher Education and Research, Health, Long-Term Care and Gender Equality, Ulrike Gote, says: In Prof. Maike Sander, the Max Delbrck Center has gained an internationally renowned scientist as its new Scientific Director. I warmly welcome her to the science and healthcare metropolis Berlin. Prof. Sanders expertise and experience provide the ideal background for future development of the MDC and for increasing the international visibility of the vibrant life sciences community at the MDC and in Berlin. As the senator in charge of higher education, research, and gender equality, I am delighted to see a woman at the helm of a Helmholtz Health Center.

I got to know Maike Sander as an expert in diabetes and stem cells when she was a visiting professor at the MDC, says OtmarD.Wiestler, President of the Helmholtz Association. With her high scientific standing and international experience, she is the ideal person to determine the future direction of the MDC as Scientific Director and Chair of the Board. With Prof. Sander we are gaining an excellent scientist whose expertise will be of tremendous benefit to the Helmholtz Association. A critical focus area is the development of precision medicine approaches. The MDC is at the forefront of advancing research in this important area. I look forward to working with Prof. Sander and to a vivid exchange of ideas.

Maike Sander, a native of Gttingen, is 54 years old. After graduating with a medical degree from the University of Heidelberg Medical School in 1994, she conducted research at the University of California, San Francisco. Before moving to UC San Diego in 2008, she held faculty positions at Hamburg Medical School and the University of California, Irvine. An expert on insulin-producing pancreatic beta cells, she has nearly 30 years of experience in medicine and diabetes research.

Sander is an elected member of the German National Academy of Sciences Leopoldina, the Association of American Physicians, and the American Society of Clinical Investigation. In addition, she is a member of two NIH consortia: The Human Islet Research Network and the NIH Impact of Genomic Variation on Function Consortium, which seeks to define basic mechanisms of gene regulation.

She is a recipient of the Grodsky Award of the Juvenile Diabetes Research Foundation, the 2022 Albert Renold Prize of the European Association for the Study of Diabetes, and the Alexander von Humboldt Foundation Research Award. Since 2019, Sander has been an Einstein Visiting Fellow at the Berlin Institute of Health at Charit (BIH).

30 Years MDC

Sander Laboratory and Publications at University of California, San Diego

German Federal Ministry of Education and Research (BMBF)Division for Press; Social Media; InternetKapelle-Ufer 110117 Berlin+49-(0)30-1857-5050presse@bmbf.bund.de

Jutta Kramm Head of the Staff Unit CommunicationsMax Delbrck Center for Molecular Medicine in the Helmholtz Association (MDC)+49-(0)30-9406-2140jutta.kramm@mdc-berlin.de or presse@mdc-berlin.de

The Max Delbrck Center for Molecular Medicine in the Helmholtz Association (MDC) is one of the worlds leading biomedical research institutions. Max Delbrck, a Berlin native, was a Nobel laureate and one of the founders of molecular biology. At the MDCs locations in Berlin-Buch and Mitte, researchers from some 60 countries analyze the human system investigating the biological foundations of life from its most elementary building blocks to systems-wide mechanisms. By understanding what regulates or disrupts the dynamic equilibrium in a cell, an organ, or the entire body, we can prevent diseases, diagnose them earlier, and stop their progression with tailored therapies. Patients should benefit as soon as possible from basic research discoveries. The MDC therefore supports spin-off creation and participates in collaborative networks. It works in close partnership with Charit Universittsmedizin Berlin in the jointly run Experimental and Clinical Research Center (ECRC), the Berlin Institute of Health (BIH) at Charit, and the German Center for Cardiovascular Research (DZHK). Founded in 1992, the MDC today employs 1,600 people and is funded 90 percent by the German federal government and 10 percent by the State of Berlin.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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CRISPR-Cas12a Editing Rates Improve with Better Directions to the Nucleus – Genetic Engineering & Biotechnology News

Posted: June 22, 2022 at 1:59 am

An appealing alternative to the Streptococcus pyogenes CRISPR nuclease SpyCas9, are Type V CRISPR Cas12a nucleases, commonly isolated from Acidaminococcus (Asp) and Lachnospiraceae (Lba). These Cas12a nucleases embody several desirable attributes that SpyCas9 lacks: they exhibit greater editing precision, recognize a thymine-rich PAM (protospacer adjacent motifa two-to-six base sequence following the nuclease target), use a single CRISPR-RNA to detect its target, cut DNA in a staggered fashion generating overhangs, process CRISPR arrays, and have been shown to function in diverse organisms ranging from plants to mammals. However, Cas12a nucleases exhibit lower editing rates than SpyCas9 in primary cells.

In a study published in GENmagazines sister journal,GEN Biotechnology (Optimization of Nuclear Localization Signal Composition Improves CRISPR-Cas12a Editing Rates in Human Primary Cells), Scot Wolfe, PhD, professor of molecular, cell and cancer biology at the University of Massachusetts Chan Medical School and his team, increased Cas12as on-target gene editing rate to nearly 100% by engineering the configuration of the enzymes nuclear localization signal (NLS). These advancements to the Cas12a editing framework could improve the use of this nuclease to uncover functions of new genes and develop new CRISPR-based treatments.

Previous work by our laboratories and others indicated that the efficiency of Cas12a editing in CD34+ hematopoietic stem and progenitor cells could potentially be improved by increasing the efficiency of its nuclear import, said Wolfe.

In earlier studies, Wolfes team had enhanced SpyCas9 gene editing in primary cells by optimizing the NLS sequence composition and number. They had found adding one NLS at the amino-terminus and two at the carboxy-terminus of the nuclease markedly improved SpyCas9s (3xNLS-SpyCas9) editing efficiency in hematopoietic stem and progenitor cells (HSPCs). They had then added two NLSs to the carboxy-terminus of Cas12a but did not achieve the same efficiency of targeted mutagenesis as the engineered SpyCas9 with three NLSs.

Ben Kleinstiver, PhD, assistant professor of pathology at Massachusetts General Hospital and Harvard Medical School, said, Genome editing efficiency is impacted by many different variables, including the concentration of a CRISPR-Cas enzyme in the nucleus where it performs its function. Researchers have previously dedicated substantial effort to improve CRISPR nuclease expression and nuclear localization for SpyCas9, but comparatively fewer optimizations have been performed for Cas12a. (Kleinstiver was not involved in the current study).

In the current study, Wolfes team developed three NLS C-terminus variants of Cas12a where they substituted the previously used simian virus NLS (SV40) with a more efficient NLS of a proto-oncogene (c-Myc). In addition, they added a third NLS to the carboxy end to achieve an editing platform at par with 3xNLS-SpyCas9 in editing efficiency. The researchers observed increased knockout efficiency in all three Cas12a orthologs (Asp, Lba, and engineered-Asp) they tested, which suggests this triple NLS strategy could be effective in improving the activity of other members of the Cas12a family, without decreasing the enzymes inherent specificity.

The study used standard electroporation to deliver the engineered Cas12a ribonucleoproteins (RNPs) into transformed human cells lines (HEK293T, Jurkat, and K562 cells) and into primary cells (natural killer cells and CD34+ HSPCs) to improve indel frequencies.

We believe that the improved NLS sequence architecture described in this paper will increase the efficiency of genome editing by Cas12a in primary cells, thus leading to increased levels of therapeutic genome editing in a variety of applications, said Wolfe. The researchers claim this strategy of enhancing the NLS sequence can be widely applied to other Cas12a orthologs and variants with similar outcomes.

The Wolfe lab and collaborators had previously demonstrated increased activity with a new NLS framework for SpyCas, so it is exciting that they demonstrated success with a new NLS for Cas12a in this publication. It is important to have additional NLSs to test in the growing list of nucleases and cell types, said Thomas Cradick, PhD, CSO at Excision BioTherapeutics. (Cradick was not involved in the current study.)

Kleinstiver said, Luk et al., demonstrated that the efficiency of editing with various Cas12a enzymes can be improved by using a more optimal configuration of NLSs. The effect of this optimization was most striking in lipid-based transfections (nucleofections) in transformed cell lines, with a more modest improvement in primary cells, the latter of which due to already high levels of editing in primary cells.

This study resurfaces a really important consideration, that you can only edit cells as efficiently as your enzyme is designed to. There are lots of knobs to turn to optimize and improve editing efficiency, and the NLS architecture clearly plays a key role in regulating the nuclear concentration, and thus the potency, of the editor, added Kleinstiver.

Nicole Gaudelli, PhD, director and head of gene editing platform technologies at Beam Therapeutics, who was not involved in the current study, said, In addition to advancing Cas12a gene editing applications, these learnings may potentially be evaluated for other gene editing tools to further increase editing efficiencies and provide greater therapeutic benefit if higher levels of gene correction or modification can be achieved.

This study was rigorously done in multiple cell types that show the robustness of the data. I liked how they delivered Cas12 as an RNP, as this is therapeutically relevant and greatly reduces off-target editing, said Alexis Komor, PhD, assistant professor of chemistry and biochemistry at the University of California, San Diego, who was not involved in the study.

I also liked this work because it uses a very universal approach to improve editing (the modifications they made to the system can be applied to any genome editing agent), and they demonstrated its utility with multiple Cas12 enzymes (which have slightly different PAMs, which is nice). Overall, its a useful and practical study, Komor continued.

As we continue the deployment of diverse CRISPR-Cas effectors in the clinic, it is important to individually engineer each molecular machine for optimal efficiency and specificity. Here, the authors show how NLS can be optimized for enhanced activity in medically relevant human primary cells, said Rodolphe Barrangou, PhD, professor of food, bioprocessing, and nutrition at North Carolina State University (NCSU), editor-in-chief of The CRISPR Journal, and CEO of TreeCo, a company that uses CRISPR to produce genetically enhanced trees. Barrangou was not part of the current study.

Optimizing on-target mutagenesis rates whilst maintaining specificity is key for successful translation to the clinic, reaffirmed Jennifer Harbottle, PhD, a senior scientist at Horizon Discovery, who was not part of this study. The Cas12a NLS variant developed by Scot Wolfes lab holds the potential to lower dosage whilst exerting therapeutic effect.

It will be of interest to see this strategy expanded to other Type V systems, and track efficiency of delivery in a wider range of cell types and tissues, added Harbottle. Comprehensively evaluating the genomic integrity of edited cells, particularly the occurrence of structural variants and chromosomal rearrangements compared to editing by canonical Cas9 systems, will be critical to push the optimized Type V variants towards in vivo use in humans.

In future studies, Wolfe intends to continue refining Cas12a nucleases to edit specific therapeutic targets. He said, We are particularly interested in applications for certain hematopoietic disorders and muscular dystrophies.

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Crimes of the Future’s Body Politics Show an Emergent Trans Fantasy – Gizmodo

Posted: June 22, 2022 at 1:58 am

When we are first introduced to Saul Tenser (Viggo Mortensen) in Crimes of the Future, hes laid up in a bed that looks like a fleshy, rotting orchid, in extreme discomfort. Hes informed that a new hormone has entered his system, a biological measurement of the internal change that hes experiencing. In our very first moments with the main character of this film, we are already getting the groundwork for the trans allegory that underlines the entirety of David Cronenbergs latest film.

Transgender, nonbinary, and otherwise queer people have long identified with horror as a means of expressing transgressive, taboo, and otherwise unacceptable behaviors and fantasies. The mere act of existing as a trans person is coming under intense scrutiny, both politically and medically, and the laws passing through various states are dehumanizing. Is it any wonder that so many of us identify with monsters? Is it any wonder that trans people are reflected in these stories so obviously?

In Crimes of the Future, the bodies of people like Tenser, who are moving beyond human, who experience accelerated evolution syndrome, are heavily policed and regulated. There are myriad complex political agencies who are deeply concerned with Tensers bodyNew Vice and the National Organ Registry chief among them. While Tenser isnt trangender, he is considered transhumanquickly evolving beyond contemporary definitions and constraints. He considers his condition a rebellion of the body, an anarchy of biology, a revolution that he feels deep inside.

All this is very similar to many transgender experiences. The bureaucratic hoops people have to jump through to change their names, their gender, and how society sees them mirror Tensers voluntary declaration of extra-evolutionary organs to the NOR, and the seemingly impossible-to-understand red tape that comes from that. Hes asked to take consultations for medical problems, or asked just how radical are you? when faced with a horrific post-mortem opportunity. A performance artist who invites people to watch as he surgically removes naturally emergent organs, Tenser is a subject of both attraction and disgust as people flock to his underground exhibitions, at the same time that his body comes under more and more scrutiny by the political powers at the edges of narrative.

There are obvious parallels to the reaction to Tensers transhuman performances and the ways queer people are seen when they exist publicly in our own society. Drag shows, queer balls, coming out parties, Pride, how many of these moments of joyful expression are considered both disgusting by members of the public but intensely attractive to the in crowd that participates? But the key to exploring the transgender experience through the transhuman portrayal in Crimes of the Future comes from the way that Tenser reacts to these vestigial organs that are spontaneously produced by his body. They hurt him, they make it difficult for him to live, but they are also the source of his art and his sense of being. In order to survive, he must have these organs surgically removed, and he chooses to do so through a voyeuristic exhibition of his surgery. Any trans person who has medically transitioned, or even considered medically transitioning in any way, will often describe their surgeries as necessary procedures, because they are. Affirming and progressive gender-corrective surgeries benefit trans people in myriad, individual ways, including benefits to their mental, social, emotional, and bodily health. Tensers view of his own surgeries as a transhuman subject are not so different.

The body is reality, Caprice, Tensers partner and surgeon, played by La Seydoux, tells him at one point. This phrase struck me hard, because for so many trans people, there is an obsessive collection of realities that exist within the body. If your body says you are one thing and your mind another, whats the truth? In the film, bodies are also described as outer space, as expansive and unknowable, as intrinsically empty of meaning until we fill it up with meaning ourselves. It is up to us to understand our bodies place, permanence, and performance.

When Timlin (Kristin Stewart) makes a pass at him, he retreats. Hes not good at the old sex. The kind of sex that a body has with another body. Instead, he finds release through new sex, he explains, the kind of euphoric realization of a new body that comes out of surgery. Besides the sexualization of surgical procedures (which is fascinating, but not necessarily something I want to relate to trans people at large, or the generalized trans experience) there is the appearance of a sex organ made by surgery as part of this, which is often part of the trans experience. The details are a little gory, so Ill spare you, but my eyes about popped out of my head when Caprice tells Tenser that his newest procedure might have its uses.

Theres also the aspect of control that runs throughout Crimes of the Futures transhumanism. Tenser is intimately tied to the desire to control his bodywhat happens to it, who touches it, and what comes out of it. Through the film he describes what happens to him as traumatic, and that he enjoys that trauma. He also says that he wants to be open he has this desire to not only become a different body, but to show it off. To be obvious and explicit about what hes doing, to perform within his new body is a feeling that a lot of trans people often want too, the freedom to be obvious about their bodies and their gender performance.

At the end of the film, theres a question of will. Has Tenser been willing these body parts to emerge? Has he found an emergent way to become transhuman? Or is this just the next step of human biology, the inevitable path of a human body simply saying yes, its time to change? Within this we can read a transgender fantasy: if we want to change, if we know that this change is necessary, if we are in an incomplete body, it will just fix itself. We will wake up one morning and our trans bodies will be transformed into what they were supposed to be, and we will be made into a more perfect trans-human.

Crimes of the Future is in theaters now.

Want more io9 news? Check out when to expect the latest Marvel and Star Wars releases, whats next for the DC Universe on film and TV, and everything you need to know about House of the Dragon and Lord of the Rings: The Rings of Power.

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New Alzheimer’s Treatment on Horizon as Dementia Reversed for First Time in Dogs – StreetInsider.com

Posted: June 22, 2022 at 1:58 am

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Australian biotech Skin2Neuron Pty Ltd. (S2N) has what no one has to date - reversal of a dementia-like syndrome in a natural animal form of Alzheimer's disease.

SYDNEY, June 21, 2022 (GLOBE NEWSWIRE) -- With the once dominant amyloid hypothesis of Alzheimer's disease suffering yet another crushing blow this week, the field is desperate for a ray of hope. Enter S2N, a new Australian biotech pioneering an all-new neurorestorative approach, aiming to rebuild and replace the lost brain cells in Alzheimer's that underlies clinical symptoms.

In a world first, a veterinary trial led by S2N suggests the audacious concept may work. S2N's new form of cell therapy reversed the dementia-like syndrome that strikes down many older pet dogs with Alzheimer's.

Co-founder Professor Michael Valenzuela explains, "Because of deep parallels between the canine brain and human brain, and canine Alzheimer's and human Alzheimer's, I started this trial 10 years ago with the assumption that if it's going to work in humans, then it needs to work in dogs first. And the results exceeded my wildest expectations."

Dementia was reversed in more than half of the canine patients, with a clinically meaningful improvement in 80%. For many of the carers, it was a life-changing turnaround, some at the point of considering euthanasia before treatment.

Fiona Gibbs, carer of Leo, a 12-yo Pomeranian in the trial, describes the impact: "Before treatment, Leo was really bad, forgetting who we were, getting lost, and having these unpredictable episodes where he would growl and snap - it was really scary and we just couldn't go on. A few months after treatment, he started getting better, and then he was back to his normal self, and we look back at the movies and think, 'Wow, was he really that bad?'"

Leo's life-changing improvement lasted almost two years, typical of clinical recovery in the trial.

And when Valenzuela looked in the brain, the findings were remarkable, "The hippocampus, the memory centre of the brain, was packed with baby neurons and new synapses, precisely where we delivered the cells. Compared to untreated dogs, it was like night and day".

Importantly, microscopic analysis confirmed the dogs had classic Alzheimer pathology. In other words, the cell therapy worked in the setting of natural disease, a first of its kind.

"Given our doggie patients also had many of the same health issues that older people face, it gives me even greater confidence," says Valenzuela.

Stem cell pioneer Professor Brent Reynolds of the University of Florida, not connected to the study, considers it a landmark in the quest to treat brain degeneration. "Alzheimer's is an area of medicine that needs new thinking. What stands out are clinically meaningful outcomes in a natural canine model of this devastating disease. Also, the company's approach to generating cells from the same patient could solve many of the problems facingcell therapies."

The study helps pave the way for S2N to launch a world-first human trial in 2024.

Contact

Professor Michael Valenzuela

Co-founder & CEO, Skin2Neuron Pty Ltd.

[emailprotected]

+61 413 603 784 (AEST)

Related Images

Image 1: Figure 1/2

Hippocampus (memory centre) of an older dog with dementia-like syndrome successfully treated with S2N's cells. It is packed with green cells that are new neurons (brain cells) and yellow dots, new synapses (connections between brain cells).

Image 2: Figure 2/2

Same brain area in an aged untreated dog. There are no new neurons (no green cells), a few red dots (old synapses), but no new synapses (no yellow dots).

This content was issued through the press release distribution service at Newswire.com.

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Top Cell and Gene therapy-2022

Posted: June 22, 2022 at 1:56 am

About Conference

Cell gene therapy 2022takes intense pleasure and honour in welcoming you all forInternational Conference on Cell and Gene Therapyduring June 27-28, 2022 atLondon, UK. Prominent keynote speakers, plenary speeches, young research forum, poster presentations, technical workshops and career guidance sessions are involved in the conference.

The conference focusses with an exciting Theme on Exploring the advancements in Cell and Gene Therapy.This scientific session offers a great platform with its well defined scientific sessions to the audience to share and express their innovative ideas on topics like Gene Therapy, Cell Therapy, Immunotherapy, Biomarkers, Stem cell in Gene therapy, Genomics, Tissue Science and Regenerative medicine, Viral Gene therapy, Epigenetics, Proteomics, Genome Editing, Nanotherapy, Advanced Gene Therapeutics and much more .

Significance of Cell and Gene Therapy Conference:

Celland gene TherapyConferences is enhance propelsmethodsand presentationof recentimprovement to the revelation of advances in Cell andgenetic field and Genetherapyis usefulin inadequate qualitiesresponsiblefor treatment of diseases usingadvancement and Cellular Therapieswhich is efficaciousto deliver Regenerative Cells and aides in quality in Cellular development of Tissues.

Cellgene Therapy2022 provides aUniversal Platformto fulfilandprovideinnovative researchon Novel andfuturemethodologies in assuaging infectionsand provides combination of Researchers, Geneticist, Biologists ,Business Delegates of Specificcompaniesand Scientiststo fulfilandprovideconcerningrecentstrategiesand Advances onthe variouscircle. Cellgene Therapy2019 Conferences main concentration is uniting Scientists, Physicians, Internationalmixof driving Universities, Celltherapy institutionsto share their examination valuable for restoring of Genet, diseasesandfacilitatein approaches for newstrategies through our Conference.

Cellgene Therapy 2022canaddress keyproblemsregardingdiseaseviewpoints in Genetic and Hereditary malady andencouragesin achieving learningreceptiveto society.

Target Audience:

Track :1 .Cell and gene therapy

Quality treatment is portrayed as a course of action of approaches that modify the announcement of a man's characteristics or repair abnormal characteristics. Each framework incorporates the association of a specific nucleic destructive (DNA or RNA). Nucleic acids are consistently not taken up by cells, subsequently exceptional transporters; implied 'vectors' are required. Vectors can be of either prominent or non-viral nature however Cell treatment is described as the association of living whole cells into the patient for the treatment of a disease. The start of the cells can be from a comparative individual (autologous source) or from another individual (allogeneic source). Youthful microorganisms are associated concerning bone marrow transplantation particularly. Diverse systems incorporate the utilization of practically create cells, isolated in vitro (in a dish) from foundational microorganisms.

Track :2 Cell damage and adoption

Cell harm can happen because of cell damage, and cell damage can additionally happen because of progress in cell's condition because of outside or inward boosts. At the point when a cell couldn't adjust and repair itself to this evolving condition, cell demise happens. Cell demise is of 2 composes Apoptosis (Programmed Cell passing) and Necrosis (Cell demise because of damage).

Track : 3. Markets and future prospects for gene therapy

The enormous number of associations related with cell treatment has extended development incredibly in the midst of the past couple of years. In excess of 500 associations have been recognized to be locked in with cell treatment and 305 of these are profiled 291 co-tasks. Of these associations, 170 are related with foundational microorganisms. The Profiles of 72 academic establishments in the US related with cell treatment close by their business facilitated endeavors. Allogeneic development with in excess of 350 clinical preliminaries is prepared to charge the commercialization of cell medicines in publicize. Progress R&D in cell and quality treatment is depended upon to bloom given the normally based purposes of intrigue.

Track: 4.Cell science research

Research in Cell Science thinks about cells their structure, physiological properties, the organelles they contain, their life cycle, division, end and cell work interchanges with their condition.

Track: 5.Molecular basis of Epigenetics

Epigenetics alludes to changes amid a body that has effect on cistron movement and articulation. It's furthermore acclimated portray any inheritable constitution alteration that does not get from a change of the body proportionate to prions. Epigenetics is that the instrument for putting away and sustaining or proceeded with uncertainly a "memory" at the cell level. Body substance might be a dynamic structure that incorporates presumably numerous signs from the cell surface and has impacts of facilitated and satisfactory transcriptional reaction in cell. It's more unmistakably that epigenetic stamping of body substance and polymer itself is an essential piece of the phone flag joining of whole works that is performed by the request. Besides, the progressions inside the epigenetic condition of body substance in cell will effectsly affect movement changes.

Track :6 Cell and gene therapy for rare common diseases

Gene therapy is a superior method to treat uncommon hereditary maladies; fix a solitary quality deformity by presenting a 'right' quality. The main quality treatment preliminaries were directed utilizing patients with uncommon monogenetic issue, however these are presently dwarfed by the clinical testing of quality therapeutics for more typical conditions, for example, malignancy, AIDS and cardiovascular illness. This is halfway because of an inability to accomplish long haul quality articulation with early vector frameworks, a basic prerequisite for amending numerous innate hereditary deformities. Presently, with the appearance of adeno-related viral (AAV) and lent viral vectors, which show steady quality articulation in creature thinks about, this mechanical obstruction, may have been survived. These vectors are foreseen to shape the premise of numerous gene therapy protocols for acquired hereditary illnesses.

Track :7 Tissue engineering and Biomaterials

Tissue Engineering might be an arrangement of techniques that may supplant or repair broken or morbid tissues with common, manufactured, or manufactured tissue emulates. These mirrors will either be absolutely down to earth or can develop into the coveted common sense. Biomaterials assume relate fundamental part in prescription todayre-establishing work and encouraging mending for people when damage or disease. Biomaterials are additionally regular or counterfeit and used in utilized in medicinal applications to help, improve, or supplant broken tissue or an organic work in different dental fields.

Track :8 Regerative Medicine

Regenerative Medicine suggests a social affair of biomedical approaches to manage investigate and clinical applications which are away to supplant or "recouping" human cells, tissues or organs to restore or set up standard limits which were vexed in view of afflictions. The field of Regenerative medication has pulled in much thought as it holds the certification of recouping hurt tissues and organs in the body by supplanting hurt tissue or by stimulating the body's own particular repair segments to retouch hurt tissues or organs. It moreover may enable scientists to create tissues and organs in the lab and safely insert them inside the body. Regenerative game plans subsequently can be a dynamic progress in the field of therapeutic administrations.

Track: 9 Cell therapy and cardiovascular disorders

Cardiovascular diseases have transformed into an extending clinical issue all around. Another test in the treatment of the cardiovascular disease is cell transplantation or cell cardiomyoplasty. Extreme ischaemic harm and relentless cardiomyopathies provoke ceaseless loss of cardiovascular tissue and in the end heart frustration. Force medications wide mean to contract the over the top changes that happen when harm and to scale back possibility segments of vas ailments. Regardless, they don't upgrade the patient's close to home fulfilment or the figure more than coordinate. Unmistakable sorts of undifferentiated living beings have been used for foundational microorganism treatment.

Track: 10 Nanotechnology in Stemcells

As of late, the entomb intersection of nanotechnology in undeveloped cell science and biomedicine has prompted a developing new research field, known as undifferentiated organism nanotechnology. Immature microorganism nanotechnology is characterized as the use of nanotechnology in undifferentiated organisms innovative work, and it is described as profoundly fast being developed, exceedingly interdisciplinary, and very disputable.

Track: 11 Stem Cell therapy

Stem Cell therapy treatment is a sort of treatment wherein undeveloped cell are utilized particularly to keep a specific malady. Undeveloped cells these days have been progressively utilized for the treatment of neurological issue, cardiovascular clutters, and numerous others. On-going investigations are continuing for the treatment of Spinal rope damage also. Hence, Stem cell treatment has an incredible breadth in future also.

Track: 12 Viral gene therapy

Customary methods for quality treatment fuse transfection. It twisted up evidently inefficient and confined fundamentally in light of transport of value into at present duplicating cells invitro. Quality treatment utilizes the transport of DNA into cells by techniques for vectors, for instance, natural nanoparticles or viral vectors and non-viral methodologies. The Several sorts of diseases vectors used as a piece of value treatment are retrovirus, adenovirus, adeno-related contamination and herpes simplex contamination. While other recombinant viral vector structures have been delivered, retroviral vectors remain the most surely understood vector system for quality treatment traditions and most prominent application in view of their undeniable significance as the essential vectors made for powerful quality treatment application and the soonest phases of the field of value treatment.

Track: 13 Gene editing and CRISPR based technologies

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) Technology is a champion among the most proficient yet clear mechanical assembly for genome adjusting. It urges and empowers experts to easily change DNA groupings and modify quality limits. It has various potential applications that join helping innate diffuses, treating and keeping the spread of diseases and upgrading crops. CRISPR broadly used as CRISPR-Cas9 where CRISPRs are particular reaches out of DNA and Cas9 is the protein which is an exacerbate that shows like a few nuclear scissors, fit for cutting DNA strands. The certification of CRISPR advancement anyway raises moral stresses as it isn't 100% powerful. Regardless, the progression of CRISPR-Cas9 has vexed the designed science industry nowadays, being a direct and great quality modifying mechanical assembly.

Track: 14 Regularity and safty aspects of cell gene therapy

Cell treatment things require a grouping of prosperity considerations. Undifferentiated living being and quality things are heterogeneous substances. There are a couple of zones that particularly ought to be tended to as it is extremely not the same as that of pharmaceuticals. These range from making bunch consistency, thing soundness to thing prosperity, quality and sufficiency through pre-clinical, clinical examinations and exhibiting endorsement. This review traces the present headings/manages in US, EU, India, and the related challenges in making SCBP with complement on clinical edge.

Track: 15 Markets and future prospects for Cell and gene therapy

The gigantic number of associations related with cell treatment has extended development incredibly in the midst of the past couple of years. In excess of 500 associations have been recognized to be locked in with cell treatment and 305 of these are profiled 291 co-tasks. Of these associations, 170 are related with foundational microorganisms. The Profiles of 72 academic establishments in the US related with cell treatment close by their business composed endeavors. Allogeneic development with in excess of 350 clinical preliminaries is prepared to charge the commercialization of cell medicines in promote. Progress R&D in cell and quality treatment is depended upon to bloom given the normally based purposes of intrigue.

Track: 16 Gene therapy for diseases

Gene therapy is the addition of particular qualities at some particular destinations into a person's cells or tissues to treat a malady, in which the faulty or non-working quality is then supplanted with the working gene.

Track:17 Cellbiology

Cell science is the investigation of cell and how the cell capacities. Cell comprise of numerous organelles that perform particular capacities and assume an imperative part in the development and advancement of a living being. Cells are of 2 writes Prokaryotic Cell and Eukaryotic Cell. Case of a Prokaryotic Cell incorporates, Bacteria, then again Animal Cell and Plant Cell are described as Eukaryotic Cells.

Track:18 Nucleotide based vaccines

Recent advances effectively prescribe that educational RNA rather than DNA will be the ester reason for a substitution classification of antibodies and medications in advertise. Nucleotide-based immunizations connected to a vast fluctuate of irresistible and threatening illnesses. We tend to focus on late routes intended to support their work and exactness. We tend to are concentring on new ways and investigate figure future advancements that may bring about the essential achievement of macromolecule immunizations inside the bar and treatment of human unwellness.

Track:19 Cancer cells and Biomarkers

Malignancy cells Integrated from Healthy cells from multiple points of view that Access them to become out of administration and move toward becoming Metastasis. One imperative refinement is that growth cells territory unit less specific than conventional cells. That is, while customary cells develop into frightfully particular cell assortments with particular capacities, disease cells don't. This is regularly one reason that, as opposed to customary cells, growth cells still separation no end. Incidentally, willcer cells can initiate close conventional cells to make veins that furnish tumors with O and supplements that they need to develop. These veins conjointly take away waste item from tumors. Biomarkers region unit particles that demonstrate customary or unusual technique occurring in your body and will be an indication of partner degree fundamental condition or sickness. Various sorts of atoms acknowledge deoxyribonucleic corrosive (qualities), proteins or hormones, will work biomarkers, since every one of them show one thing in regards to your wellbeing. Biomarkers could likewise be made by the disease tissue itself or by elective cells inside the body because of malignancy.

Track:20 Genetics and Genomic medicine

Hereditary qualities are that the branch of science required with qualities, heredity, and variety in living life forms. It looks to get a handle on the strategy for ascribe legacy from oldsters to posterity, and also the sub-atomic structure and execution of qualities, succession conduct inside the setting of a cell or living being (e.g. predominance and epigenetics), cistron circulation, and variety and adjust in populaces.Genomic drugs, by and large also conjointly redid drugs, might be on account of alter restorative guide to your body's unmistakable hereditary cosmetics. Everything about cells inside the body contains deoxyribonucleic corrosive, the particles you acquire from your people that confirm anyway your body appearance and capacities. Deoxyribonucleic corrosive is composed kind of a wound stepping stool, with information keep inside the course of action, or succession, of the rungs. Segments of the polymer step that contain information required to shape proteins are alluded to as qualities. The entire structure is that the request. A practically total guide of the polymer arrangement was finished in 2003, and from that point forward, researchers have attempted to get a handle on anyway every factor capacities and the way it's planned with every elective factor. The human request may contain 20 000 to 23 000 qualities.

Cell gene therapy 2022 cordially invites you all to join us on International Conference on Cell and Gene Therapy scheduled during June 27-28, 2022 at London, UK. The conference was taking place under the theme on Exploring the advancements in Cell and Gene Therapy.

For more details:https://genetherapy.geneticconferences.com/

Scope: Scope of the meeting isto assembleeach oneof the Doctors, Researchers, Business Delegates and Scientists to approach and conveyeach oneof the participantsregardingthe premiercurrentlogical headways.It is thevariable circle or associated logical controls .This Cell and succession treatment Conference is thatthe topknowledgeunderstanding individual and structure conduct and basic leadership withrelevancescience examination andbioscience, biotechnology,pharmaceuticals, medicals andother areas.

Importance: Gathering on Cell therapeutic carecan bea bottomless praised meeting thatessentiallymanagesthe foremost current investigationand enhancementswithinthe circle of Cell andnatural science. This Conferencewillprovides a excellentstage to any or all the Internationalmixof driving investigation understudies, and Scientists accomplished distinction in their field of study, examination academicians fromthe universitiesand investigation foundations, mechanical examinationspecialistsand business connectsalong sidepHscaled. Understudies tocome backand educateeach oneof the participants withreference tothe most recentlogical headways on the few circles.

Why London???

Londonis the stunning capital city of UK, and is one of the most charismatic and vibrant cities of United kingdom. It is a city that effortlessly blends traditional heritage, with striking modernism and progressive thinking.As a holiday destination,Londonoffers a rich and varied history, a buzzing nightlife and is blessed with a glorious year-round climate.Londonis a bustling and exciting city, that boasts a wide choice of activities and fascinating tourist attractions. The city has a welcoming and liberal atmosphere, while still embracing its deep-rooted heritage and extensive history. Lisbon will appeal to a diverse selection of ages and tourists; it can form a cultural trip, a nightlife extravaganza, a family holiday, a relaxed city-break or even as a base for a beach holiday. Lisbon has hot dry summers, pleasant springs and autumns, and mild, but possibly wet winters. The best time of year to visitLondonis in the late spring (May-June) when the days are bright and sunny, but the temperatures are not so high. The peak season is between June and August, and if you visit at this time of year, you should expect the city to feel crowded. The weather is suitable for spending time on the beach from May until the end of September.

Global Cell Therapy Market:

Cellmedicinalguide item, that region unit got fromdedifferentiatedcells, tissues, and organs develop in labs, region unit infused into patients. The developing assortment of clinical preliminaries, government and individualfinance, andincreasingscope of associations betweencorporationsterritory unit driving the extension ofthe globecell restorative guide advertise. "Cell and Sequence restorative guide item that region unitofferedwithinthe market depends onautologousand allogeneic cells. Theraiseof cell treatment isincreasing."

Quality restorative guide includesconnectionofanengineeredor amodifiedsuccession misusemodified irresistible operator vectors that encourage convey the grouping atimplicitsiteof activityor evenexecute the cellwhich cancause thedisease. This treatment is forthe foremostparta one-time treatment orwantssimplyfew measurements of prescription tofullyfix thedisease.

The examiners estimatethe globecell therapeutic guide market to develop at a CAGR of9.5%duringtheyear 2019-2026. The report coversthisscenarioandonthese linesthe eventprospects ofthe globecell therapeutic guidebusinesscenter for 2019-2026. The report introducesa close-byimageof the market bystrategiesfor study, blend, and summationof informationfromvariedsources.

Top Universities around the Globe

Statistical Analysis of universities

List of Companies Associated with Cell and Gene Therapy Research

Top Major Societies Associated with Cell and Gene Therapy

Pie Chart between Companies and Societies associated

Market Value on Cell and Gene Therapy

Genemedical caremay be aattractiveareafor drug development as aresult ofwiththe propertarget and approach;it willaddressthe premisereason for a severemalady.Evidentlydisorderswhereacknowledged genetic mutationsas a result ofdeficient or non-functionalmoleculeproduction, sequencemedical carecanfix the underlying defectand providea pathto producethe sensiblemolecule.

The worldwide sequencemedical caremarket was valued at $584 million in 2016, and isdeterminabletoreach$4,402 million by 2023, registering a CAGR of33.3% from 2017 to 2023.the increasein funding for R&D activitiesreferring tosequencemedical careand increase in awarenessregardingsequencemedical aidunitthe foremostvitalfactors that drive the market growth.

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Top Cell and Gene therapy-2022

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