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Archive - 2019

October 22nd

Takeda Acquires License for First-in-Class Celiac Disease Therapy from COUR Pharmaceuticals Following Positive Phase 2a Proof-of-Concept Study

On October 22, 2019, Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) and COUR Pharmaceutical Development Company, Inc. (“COUR”) announced that Takeda has acquired an exclusive global license to develop and commercialize the investigational medicine CNP-101/TAK-101, an immune-modifying nanoparticle containing gliadin proteins. Based on COUR’s antigen-specific immune tolerance platform, TAK-101 is a potential first-in-class treatment targeting the aberrant immune response in celiac disease, a serious autoimmune disease where the ingestion of gluten leads to inflammation and damage in the small intestine. Results of a randomized, double-blind, placebo-controlled clinical trial to assess the markers of potential efficacy and safety of the investigational medicine in 34 adults with proven celiac disease was presented on October 22, 2019 as a late-breaking abstract at UEG Week 2019, Barcelona, Spain (https://live.ueg.eu/week/). At inclusion, patients had well-controlled, biopsy-proven celiac disease. After inclusion, they underwent an oral gluten challenge. Based on the study, Takeda exercised its option to acquire the exclusive global license to TAK-101. “While many people living with celiac disease can manage their symptoms by following a gluten-free diet, there are currently no treatment options for those who continue to have symptoms,” said Asit Parikh MD, PhD, Head, Gastroenterology Therapeutic Area Unit at Takeda. “Our collaboration with COUR has shown, for the first time, that it is possible to induce specific immune tolerance to a foreign antigen in autoimmune diseases such as celiac disease.

New Treatment May Reverse Celiac Disease; Novel Nanotechnology Approach May Be Applicable to Other Autoimmune Diseases and Allergies, Including Multiple Sclerosis, Type 1 Diabetes, & Asthma; Takeda Acquires License for First-in-Kind Celiac Disease Therapy

Results of a new phase 2 clinical trial using technology developed at Northwestern Medicine show it is possible to induce immune tolerance to gluten in individuals with celiac disease. The findings may pave the way for treated celiac patients to eventually tolerate gluten in their diet. After treatment with the technology, the patients were able to eat gluten with a substantial reduction in inflammation. The results also show a trend toward protecting patients' small intestine from gluten exposure. The findings were presented as a late-breaking presentation on October 22 at the European Gastroenterology Week 2019 conference in Barcelona, Spain (October 19-23) (https://live.ueg.eu/week/). The technology is a biodegradable nanoparticle containing gluten that “teaches” the immune system that the antigen (allergen) is safe. The nanoparticle acts like a Trojan horse, hiding the allergen in a friendly shell, to convince the immune system not to attack it. Beyond celiac disease, the finding sets the stage for the technology -- a nanoparticle containing the antigen triggering the allergy or autoimmune disease -- to treat a host of other diseases and allergies including multiple sclerosis, type 1 diabetes, peanut allergy, asthma, and more. The technology was developed in the lab of Stephen Miller, PhD, Professor of Microbiology and Immunology at Northwestern University Feinberg School of Medicine, who has spent decades refining the technology. "This is the first demonstration the technology works in patients," said Dr. Miller, the Judy Gugenheim Research Professor of Microbiology and Immunology.

October 21st

Autism Spectrum Disorder Risk Linked to Insufficient Placental Steroid (ALLO); Single ALLO Injection During Pregnancy Enough to Avert Cerebellar Abnormalities and Aberrant Social Behaviors In Experimental Models

A study in experimental models suggests that allopregnanolone (ALLO), one of many hormones produced by the placenta during pregnancy, is so essential to normal fetal brain development that when provision of that hormone decreases or stops abruptly - as occurs with premature birth - offspring are more likely to develop autism-like behaviors. A Children's National Hospital research team reports the findings Oct. 20, 2019, at the Neuroscience 2019 annual meeting in Chicago (October 19-23) (https://www.sfn.org/meetings/neuroscience-2019). The presentation was titled “"Preterm ASD Risk Linked to Cerebellar White Matter Changes.” "To our knowledge, no other research team has studied how placental allopregnanolone (ALLO) contributes to brain development and long-term behaviors," says Claire-Marie Vacher, PhD, lead author. "Our study finds that targeted loss of ALLO in the womb leads to long-term structural alterations of the cerebellum - a brain region that is essential for motor coordination, balance, and social cognition - and increases the risk of developing autism," Dr. Vacher says. According to the Centers for Disease Control and Prevention, about 1 in 10 infants is born preterm, before 37 weeks gestation; and 1 in 59 children has autism spectrum disorder. In addition to presenting the abstract on Sunday, Anna Penn, MD, PhD, the abstract's senior author, discussed the research with reporters on Monday, October 21, during a Neuroscience 2019 news conference. This Children's National abstract is among 14,000 abstracts submitted for the meeting, the world's largest source of emerging news about brain science and health. ALLO production by the placenta rises in the second trimester of pregnancy, and levels of the neurosteroid peak as fetuses approach full term.

5-Year Funding of $71 Million to Spur Efforts of Trans-Atlantic Collaboration (ACED) of Five Institutions in UK and US to Pursue Earliest Possible Detection of Cancers

Developing radical new strategies and technologies to detect cancer at its earliest stage is the bold ambition of a new trans-atlantic research alliance—the International Alliance for Cancer Early Detection (ACED) -- announced on October 21, 2019 by Cancer Research UK and partners, and to be funded by over £55 million (~$71 million) over the next five years. Early detection is essential to help more people beat cancer – a patient’s chance of surviving his or her disease improves dramatically when cancer is found and treated earlier. Understanding the biology of early cancers and pre-cancerous states will allow doctors to find accurate ways to spot the disease earlier and, where necessary, treat it effectively. It could even enable “precision prevention” – where the disease could be stopped from ever occurring in the first place. UK statistics highlight the major improvements in survival that could be achieved. 5-year survival for six different types of cancer is more than three times higher if the disease is diagnosed at stage one, when the tumor tends to be small and remains localized, compared with survival when diagnosed at stage four, when the cancer tends to be larger and has started to invade surrounding tissue and other organs. Advances in early-detection technologies will help decrease late-stage diagnosis and increase the proportion of people diagnosed at an early and treatable stage, so a future for more patients can be secured. Cancer Research UK is setting out a bold ambition to jump-start this under-explored field of research in a collaboration with teams of scientists from across the UK and the US.

October 20th

Researchers Quantify Cas9-Caused Off-Target Mutagenesis in Mice; Thoughtful Design of Guide RNAs Can Significantly Limit Off-Target Mutagenesis; Inbred Lines Show Surprising Number of Natural Mutations

Scientists are finding new ways to improve the use of the CRISPR enzyme Cas9 and reduce the chances of off-target mutations in laboratory mice, according to new results from a research collaboration including Lauryl Nutter (photo), PhD, Senior Director, Science and Technology Development at The Centre for Phenogenomics at The Hospital for Sick Children (SickKids) in Toronto, Canada The findings, which help scientists contextualize a common concern related to gene editing and identify new strategies to improve its precision, were presented on October 18, 2019 as a featured plenary abstract at the American Society of Human Genetics (ASHG) 2019 Annual Meeting in Houston (October 15-19). The presentation abstract (https://eventpilotadmin.com/web/page.php?page=IntHtml&project=ASHG19&id=...) is titled “Whole Genome Sequencing Puts Cas9 Off-Target Mutagenesis into the Context Of Genetic Drift.” Dr. Nutter and her collaborators from the multi-institution Knockout Mouse Phenotyping Project (KOMP2) regularly use Cas9 and gene editing to produce lines of laboratory mice with specific mutations. In this work, they often encounter questions about the likelihood of off-target mutagenesis – unintended genetic mutations introduced by the gene-editing process – in their mouse lines. “We wanted to know: to what extent do we need to worry about off-target mutagenesis?” Dr. Nutter explained. By demonstrating the degree of the problem in mice, the researchers hoped to be better able to evaluate it in human cell lines being studied in the laboratory, as well as generate new ways to improve the precision of Cas9-based gene editing.

October 19th

Cystic Fibrosis Carriers at Increased Risk of Digestive Symptoms

Researchers have found that carriers of the most common genetic variant that causes cystic fibrosis experience some symptoms similar to those of people with cystic fibrosis. These findings were enabled by large-scale genomic data made available just a few years ago. Yu-Chung (Jerry) Lin, BA, MSc, a graduate student at the University of Toronto, presented the research on October 17, 2019 at the American Society of Human Genetics (ASHG) 2019 Annual Meeting in Houston, Texas (October 15-19). The presentation abstract is titled “Defining the Phenotypic Signature of CFTR Mutation Carriers in the UK Biobank.” Cystic fibrosis is a recessive disease caused by variants of the CFTR gene, which means that affected individuals have two such variants. It affects many organs, and symptoms vary from patient to patient. They can include lung function decline, intestinal obstruction, diabetes, and pancreatic dysfunction. The extent of a person’s symptoms can be affected by modifier genes, which do not directly cause cystic fibrosis, but can affect how an individual’s experience of the disease. Researchers have long assumed that carriers, who have one copy of a disease-causing CFTR variant, do not experience any symptoms. However, given the disease’s wide breadth of symptoms, Mr. Lin explained, researchers needed a very large sample size to definitively answer this question. Senior author Lisa Strug, PhD, Associate Director of The Centre for Applied Genomics at The Hospital for Sick Children, explained, “Although many individuals are learning of their CFTR carrier status through family planning or the use of personal genomics companies, researchers have not yet thoroughly investigated whether a phenotype for cystic fibrosis carriers exists.”

Metabolic Dysfunction in Mitochondria & Not Protein Accumulation Is Key Cause of Alzheimer’s Disease, New Study Shows; Common Anti-Diabetes Drug (Metformin) Identified As Potential Treatment

A team of researchers led by Yale-National University of Singapore (NUS) College scientists has found evidence that metabolic dysfunction is a primary cause of Alzheimer’s disease. Alzheimer’s disease is the most common neurodegenerative disease affecting the elderly worldwide, as well as one of the most common causes of dementia. In Singapore, 1 in 10 people aged 60 or above is believed to suffer from dementia. After more than twenty years of research effort worldwide, scientists are still unable to identify the exact causes of Alzheimer’s and no proven treatment is available. Two competing theories are currently proposed to explain the cause of Alzheimer’s: the first is focused on the accumulation of a specific protein, called amyloid-beta protein, in the brain as the primary cause; whilst a second and more recent theory proposes that metabolic dysfunction, specifically a dysfunction of the cell’s energy-producing machinery called mitochondria is responsible. In a new study published online on October 18, 2019 in eLife (https://elifesciences.org/articles/50069), a team led by Assistant Professor of Science (Biochemistry) Jan Gruber, PhD, from Yale-NUS College discovered that metabolic defects occur well before any significant increase in the amount of amyloid-beta protein could be detected. The open-access article is titled "Metabolic Stress Is a Primary Pathogenic Event In Transgenic Caenorhabditis Elegans Expressing Pan-Neuronal Human Amyloid Beta." The research used a tiny worm called Caenorhabditis elegans to identify these changes because this worm shares many similarities at the molecular level with human cells.

October 16th

Mice with Hyper-Long Telomeres Show Less Metabolic Aging and Longer Lifespans; Scientists Generate Mice Having 100% of Their Cells with Hyper-Long Telomeres: Results Said to be “Unprecedented”

A chance finding ten years ago led to the creation by researchers of the Spanish National Cancer Research Centre (CNIO) of the first mice born with much longer telomeres than normal in their species. Given the relationship between telomeres and aging (telomeres shorten throughout life, so older organisms have shorter telomeres), scientists launched a study generating mice in which 100% of their cells had hyper-long telomeres. The findings were published online on October 17, 2019, in Nature Communications (https://www.nature.com/articles/s41467-019-12664-x) and show only positive consequences: the animals with hyper-long telomeres live longer in better health, free from cancer and obesity. The most relevant result for the authors is that longevity has been significantly increased for the first time ever without any genetic modification. "This finding supports the idea that, when it comes to determining longevity, genes are not the only thing to consider,” indicates Maria Blasco (https://www.cnio.es/en/personas/maria-a-blasco-2/) (https://en.wikipedia.org/wiki/Mar%C3%ADa_Blasco_Marhuenda), PhD, Head of the CNIO Telomeres and Telomerase Group at CNIO, Director of the Spanish National Centre for Cancer Research, and intellectual author of the paper. "There is margin for extending life without altering the genes.” The open-access article is titled “Mice with Hyper-Long Telomeres Show Less Metabolic Aging and Longer Lifespans.” Telomeres form the end of chromosomes, in the nucleus of each cell in the body. Their function is to protect the integrity of the genetic information in DNA. Whenever the cells divide the telomeres are shortened a little bit, so one of the main characteristics of aging is the accumulation of short telomeres in cells.

October 16th

Researchers Develop Mouse Model Incorporating Human Gene (MAPT) Involved in Alzheimer’s Disease

In research that helps scientists better understand and explore treatments for diseases like Alzheimer’s, scientists have developed a line of mice in which the mouse version of the Alzheimer’s-associated MAPT gene has been fully replaced by the human version of the gene. In this new animal model, known as a full-gene-replacement model, the MAPT gene will function the same way it does in humans, allowing researchers to more accurately develop and evaluate genetic therapies. The research was presented on October 16 at the American Society of Human Genetics (ASHG) 2019 Annual Meeting in Houston, Texas (October 15-19). The presentation abstract is titled “Moving Human Genetics into the Mouse: Full Human Gene-Replacement Models.” Scientists have long studied human genes in mice and other animal models, usually by finding and manipulating the animal’s version of the human gene being studied, explained Michael Koob, PhD, Associate Professor at the University of Minnesota, who presented the work. “However, mice have different genes than people, and even if the gene’s function is the same, its sequence is different,” Dr. Koob said. For this reason, animal model work typically involves a great deal of trial and error, and it requires researchers to make assumptions about why and how a genetic change leads to the observed changes. In addition, drawing conclusions about the role of the human version of the gene in humans – and building on this knowledge by developing therapies – is difficult and prone to error, and the findings do not always translate.

Quantifying Hispanic and Latinx Populations' Interest in Genetic Research Participation

Researchers are increasingly prioritizing the need for diversity in genetics and genomics research. To help make such studies more inclusive, José G. Pérez-Ramos, MPH, and Timothy D.V. Dye, PhD, research scientists at the University of Rochester in New York. examined Hispanic and Latinx populations’ desire to participate in genomics research. Mr. Pérez-Ramos presented the findings on October 16 at the American Society of Human Genetics (ASHG) 2019 Annual Meeting in Houston, Texas (October 15-19). The presentation abstract is titled “Variation in Intention to Participate in Genetic Research Among Hispanic/Latinx Populations by Latin America Birth-Residency Concurrence: A Global Study. “We were interested in the determinants for people to participate in genetic research,” said Dr. Dye, principal investigator on the study. “Not only is representation in research important for accuracy of results, but it also helps improve distributional justice. If Hispanic and Latinx people are not represented, then there’s no possibility of them benefitting from all of the important genetics research that’s happening.” Mr. Pérez-Ramos and colleagues surveyed 1,718 individuals from 69 countries; among whom, 251 participants self-identified as Hispanic or Latin American and Caribbean (LAC). When measured as a single group, Hispanic and LAC people were as willing to participate in genomics research studies, and felt as positively about their impact, as other groups. However, when the participants of Hispanic and LAC ancestry were segmented further by country of birth and residence, there were noticeable differences in attitudes toward, and interest in, genetic research participation.