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Archive - Jul 2019

Date

July 7th

First Complete Wiring Diagram of an Animal (C. elegans) Nervous System Established

In a study published online on July 3, 2019 in Nature, researchers at Albert Einstein College of Medicine in New York describe the first complete wiring diagram of the nervous system of an animal, the roundworm Caenorhabditis elegans, used by scientists worldwide as a model organism. The study includes adults of both sexes and reveals substantial differences between them. The Nature article is titled “Whole-Animal Connectomes of Both C. elegans Sexes.” The article findings mark a major milestone in the field of "connectomics," the effort to map the myriad neural connections in a brain, brain region, or nervous system to find the specific nerve connections responsible for particular behaviors. "Structure is always central in biology," said study leader Scott Emmons, PhD, Professor of Genetics and in the Dominick P. Purpura Department of Neuroscience and the Siegfried Ullmann Chair in Molecular Genetics at Einstein. "The structure of DNA revealed how genes work, and the structure of proteins revealed how enzymes function. Now, the structure of the nervous system is revealing how animals behave and how neural connections go wrong to cause disease." Researchers have hypothesized that some neurological and psychiatric disorders, such as schizophrenia and autism, are "connectopathies," that is, problems caused by "faulty wiring." "This hypothesis is strengthened by the finding that several mental disorders are associated with mutations in genes that are thought to determine connectivity," said Dr. Emmons. "Connectomics has the potential to help us understand the basis of some mental illnesses, possibly suggesting avenues for therapy." Because C.

July 6th

Triplet-Targeted Therapy Improves Survival for Patients with Advanced Colorectal Cancer and BRAF Mutations; Phase III Trial Results May Change Standard of Care for Up to 15% of Colorectal Cancer Patients

The three-drug combination of encorafenib, binimetinib, and cetuximab significantly improved overall survival (OS) in patients with BRAF-mutated metastatic colorectal cancer (mCRC), according to results of the BEACON CRC Phase III clinical trial led by researchers at The University of Texas (UT) MD Anderson Cancer Center. The treatment combination resulted in a median OS of 9 months for the combination therapy compared to 5.4 months for current standard-of-care treatment. Objective response rate (ORR) for the triplet-targeted therapy was 26 percent compared to just two percent for standard therapy. BEACON CRC is the first and only Phase III trial designed to test BRAF/MEK combination targeted therapies in patients with mCRC and the BRAF V600E mutation. BRAF mutations are estimated to occur in up to 15 percent of patients with mCRC, with V600E being the most common BRAF mutation and representing a poor prognosis for these patients. The trial results was reported on July 6at the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2019 (https://www.esmo.org/Conferences/ESMO-World-GI-2019) in Barcelona, Spain, by principal investigator Scott Kopetz, MD, Associate Professor of Gastrointestinal Medical Oncology at MD Anderson. The title of the report abstract is BEACON CRC: a randomized, 3-Arm, phase 3 study of encorafenib and cetuximab with or without binimetinib vs. choice of either irinotecan or FOLFIRI plus cetuximab in BRAF V600E–mutant metastatic colorectal cancer. "This study builds on a decade of research into the tumor biology of BRAF-mutated colorectal cancer, and reflects a rationale combination to address the vulnerabilities unique to this tumor," said Dr. Kopetz.

Strain of Oncolytic Common Cold Virus (Coxsackievirus A21) Could Revolutionize Treatment of Bladder Cancer

A strain of the common cold virus has been found to potentially target, infect, and destroy cancer cells in patients with bladder cancer, a new study published online on July 4, 2019 in Clinical Cancer Research reports. No trace of the cancer was found in one patient following treatment with the virus. In the majority of the other 14 treated patients, evidence of cancer cell death was observed. The title of the article is “Viral Targeting of Non-Muscle Invasive Bladder Cancer and Priming of Anti-Tumour Immunity Following Intravesical Coxsackievirus A21.” Researchers from the University of Surrey and Royal Surrey County Hospital investigated the safety and tolerability of exposure to the oncolytic (“cancer-killing”) virus coxsackievirus (CVA21), a naturally occurring strain of the common cold virus, in fifteen patients with non-muscle invasive bladder cancer (NMIBC). NMIBC is found in the tissue of the inner surface of the bladder and is the tenth most common cancer in the UK with approximately 10,000 people each year diagnosed with the illness. Current treatments for this cancer are problematic. Transurethral resection, an invasive procedure that removes all visible lesions, has a high tumor recurrence rate ranging from 50 per cent to 70 per cent as well as a high tumor progression rate between 10 per cent and 20 per cent over a period of two to five years. Another common course of treatment, immunotherapy with Bacille Calmette-Guerin (BCG), a live bacterium used to treat bladder cancer, has been found to have serious side effects in one third of NMIBC patients, while one third do not respond to the treatment at all. During this pioneering study, fifteen NMIBC patients, one week prior to pre-scheduled surgery to remove their tumors, received CVA21 via a catheter in the bladder.

July 4th

Tiny Molecular Change Reverses Prediabetes in Obese Mice; Remarkable Results Point to Potential Diabetes Drug Target and Highlight Possible Role for Ceramides in Sensing Nutrition

A small chemical change -- shifting the position of two hydrogen atoms -- makes the difference between mice that are healthy and mice with insulin resistance and fatty liver, major risk factors for diabetes and heart disease. Making the change prevented the onset of these symptoms in mice fed a high-fat diet and reversed prediabetes in obese mice. The scientists changed the trajectory of metabolic disease by deactivating an enzyme called dihydroceramide desaturase 1 (DES1). Doing so stopped the enzyme from removing the final hydrogens from a fatty lipid called ceramide, having an effect of lowering the total amount of ceramides in the body. The finding highlights a role for ceramides in metabolic health and pinpoints DES1 as a "druggable" target that could be used to develop new therapies for metabolic disorders such as prediabetes, diabetes, and heart disease -- that affect the health of hundreds of millions of Americans. Scientists at University of Utah Health and Merck Research Laboratories led the research, published online in Science on July 4, 2019. The article is titled “Targeting a Ceramide Double Bond Improves Insulin Resistance and Hepatic Steatosis.” "We have identified a potential therapeutic strategy that is remarkably effective, and underscores how complex biological systems can be deeply affected by a subtle change in chemistry," says Scott Summers (at right in photo), PhD, Chair of Nutrition and Integrative Physiology at U of Utah Health, who was co-senior author on the study with David Kelley, MD, formerly of Merck Research Laboratories. "Our work shows that ceramides have an influential role in metabolic health," says Dr. Summers. "We're thinking of ceramides as the next cholesterol." This isn't the first time that Dr.

Scientists Apply Bacterial Homing Capability to Enable Stem Cells to Home to Heart Tissue; Approach Offers “Enormous Potential” for Millions Suffering from Heart Disease Around the Globe

In a world first, scientists have found a new way to direct stem cells to heart tissue. The findings, led by researchers at the University of Bristol in the UK and published recently in Chemical Science, could radically improve the treatment for cardiovascular disease, which causes more than a quarter of all deaths in the UK. The open-access article is titled “Designer Artificial Membrane Binding Proteins to Direct Stem Cells to the Myocardium.” To date, trials using stem cells, which are taken and grown from the patient or donor and injected into the patient's heart to regenerate damaged tissue, have produced promising results. However, while these next-generation cell therapies are on the horizon, significant challenges associated with the distribution of the stem cells have remained. High blood flow in the heart combined with various “tissue sinks” that circulating cells come into contact with, means the majority of the stem cells end up in the lungs and spleen. Now, researchers from Bristol's School of Cellular and Molecular Medicine have found a way to overcome this by modifying stem cells with a special protein so the stem cells “home” to heart tissue. Dr. Adam Perriman, the study's lead author, Associate Professor in Biomaterials, UKRI Future Leaders Fellow and founder of the cell therapy technology company CytoSeek (https://www.cytoseek.uk/), explained: "With regenerative cell therapies, where you are trying to treat someone after a heart attack, the cells rarely go to where you want them to go. Our aim is to use this technology to re-engineer the membrane of cells, so that when they're injected, they'll home to specific tissues of our choice.”