CAV3

Studying genes in families with a propensity for certain diseases has led to many critical advances in medicine, including the discovery of statins in family members who suffered heart attacks at an early age. Now, a team of researchers has identified an inherited mutation in a gene linked to a highly lethal cancer of what is commonly known as the food pipe, called esophageal adenocarcinoma (EAC). Studying genes in families with a propensity for certain diseases has led to many critical advances in medicine, including the discovery of statins in family members who suffered heart attacks at an early age. Now, a team of researchers at Case Western Reserve University has identified an inherited mutation in a gene linked to a highly lethal cancer of what is commonly known as the food pipe, called esophageal adenocarcinoma (EAC). "With this discovery, we will be able to identify early those at a high risk of developing EAC in their lifetime, and accordingly tailor screening, lifestyle and treatment strategies to prevent cancer development," said Kishore Guda, an associate professor at the Case Western Reserve School of Medicine and member of the Case Comprehensive Cancer Center. Guda led the study, published in the journal Gastroenterology,with Amitabh Chak, a professor at the School of Medicine and physician at University Hospitals Cleveland Medical Center. Their previous studies found that up to 10% of patients with EAC or Barrett's esophagus -- a precursor to EAC -- have a family member with the disease, suggesting a potential genetic predisposition. But the molecules contributing to EAC's development have been poorly understood. By studying families with the disease, they identified the gene -- Caveolin-3 (CAV3) -- that plays a critical role in its development. Caveolins (including CAV1, CAV2, CAV3) are structural components of a cell that regulate various proteins involved in the cell's ability to function properly. But until now the gene's specific role in the esophagus -- and especially in EAC -- was unknown. The researchers used molecular techniques and tissues from humans and animal models to learn what CAV3 does in the esophagus. They learned CAV3 is normally present in specialized cells -- called mucosal glands -- which are typically found beneath the surface of esophagus. And when the esophagus is injured, these CAV3-containing cells migrate up to heal the injury. "In the family where we identified CAV3 mutation," Guda said, "we show that this mutation leads to loss of its normal function and wouldn't be able to repair the injured esophagus." Implications Their discovery suggests: "This is especially relevant to individuals suffering from chronic heartburn, where the acid and bile from the stomach reaches up and injures the lower esophagus," Guda said. "These individuals are particularly at risk of developing EAC if the injured esophagus isn't repaired and healed." Up next Future work will focus on screening more families who may be carrying genetic defects in CAV3 or in other Caveolin genes; figuring out how CAV3 helps in esophageal healing and identifying strategies to correct or restore normal function of defective esophageal mucosal glands to prevent cancer risk; and making ablative therapy more effective, they said. (Ablative therapy uses extremely high or low temperatures to destroy abnormal tissue or tumors.) "There could be several reasons why normal cells become cancerous," Chak said. "By studying familial clusters of the disease, we are identifying the dangerous roads that lead to cancer so effective screening and intervention strategies can be implemented to prevent the disease before it even begins."

CHARLOTTESVILLE, Va. & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Cavion, Inc., a leading clinical stage biotechnology company committed to developing novel therapeutics for people with neurological diseases, announced today that results of the Phase 2 study of its lead compound for essential tremor will be presented as a late-breaking poster at the International Congress of Parkinson’s Disease and Movement Disorders® in Hong Kong October 5-9, 2018. Phase 2 data from @CavionPharma in #essentialtremor will be highlighted in #latebreaker at #MDSCongress in Hong Kong on October 8 with three additional posters on its first-in-class T-Type calcium channel modulator CX-8998 Cavion’s team of experts is developing oral small molecules designed to selectively modulate T-type calcium channel activity in the central nervous system, acting as a biological “pacemaker” to help restore the brain’s natural rhythms. The company’s lead compound, CX-8998, was evaluated in the T-CALM study, a Phase 2, double-blind, placebo controlled clinical trial of 95 patients with essential tremor conducted at 25 sites across the United States. Patients were randomized to receive either placebo or CX-8998 titrated up to 10mg dosed twice daily (BID). A majority of subjects (64 percent) added study drug to their existing standard of care anti-tremor medication. “Cavion is dedicated to developing first-in-class T-type calcium channel therapies aimed at improving function for people with movement disorders and rare neurological diseases, using state-of-the-art clinical development methodologies,” said Spyros Papapetropoulos, MD, PhD, Cavion’s Executive Vice President of Research & Development and Chief Medical Officer. “Our T-CALM study is one of the largest Phase 2 essential tremor clinical trials ever conducted, and CX-8998 is the only late-stage essential tremor small molecule in development for this disease. We look forward to presenting these results as we grow the body of clinical evidence supporting our ground-breaking approach in essential tremor, a disorder that has not seen any new approved drug therapies in more than 30 years.” The T-CALM study abstract was selected for a late-breaking poster presentation on Monday, October 8: “Proof-of-Concept, Double-Blind, Placebo-Controlled Study for CX-8998 a State-Dependent T-Type Calcium (Cav3) Channel Antagonist in Essential Tremor Patients (T-CALM): Efficacy and Safety Results.” Additional Cavion research to be presented at the Congress includes: Proof-of-Principle Quantitative EEG Study Of CX-8998, An Oral, Potent and Selective T-Type Calcium Antagonist in Development for Symptomatic Treatment of Essential Tremor and Parkinson’s Disease Tremor A Phase 2 Efficacy Study of CX-8998, A Potent and Selective T-Type Calcium (Cav3) Modulator in Parkinson’s Disease Tremor (PDT) Patients: Design and Dose-Selection Rationale Therapeutic Exposures of CX-8998, A Potent, Selective and State Dependent Cav3 Channel Antagonist in Development for Essential Tremor and Parkinson’s Disease Tremor in Cav3 Driven Neurological Models About Cavion, Inc. Cavion, Inc. is a privately held clinical stage biotechnology company creating therapies aimed at modulating the T-type calcium channel for the treatment of chronic and rare neurological diseases. Cavion’s portfolio of T-type calcium channel modulators is being developed to restore the brain’s natural rhythms in a variety of neurological diseases such as essential tremor, Parkinson’s disease tremor, neuropathic pain, and epilepsy with absence seizures. About Essential Tremor About 10 million Americans and 42 million people worldwide are affected by essential tremor (ET), the most common movement disorder. ET is a progressive neurodegenerative disease that ranges from mild to fully debilitating, with significant effects on people’s quality of life and activities of daily living, such as eating and drinking, dressing, writing and typing. The condition can lead to social embarrassment, phobia, anxiety, and depression. With no new drugs approved for more than three decades, there is an incredible need for new and effective options for patients with ET (Haubenberger and Hallett. 2018. Essential Tremor. New England Journal of Medicine. 378:19). Forward-Looking Statement This press release contains forward-looking statements that are subject to risks and uncertainties and includes statements that are not historical facts. Actual results could differ significantly from results discussed. Cavion, Inc. disclaims any intent or obligation to update forward-looking statements, except as required by law.