Innovative Phenotypic Screening Approach to Identify Potential Therapeutic Drugs for Rare Neurological and Muscular Disorders
(FEB. 9, 2024 – WARNER ROBINS, GA) – Cure VCP Disease, Inc., a non-profit organization dedicated to finding a cure for Valosin-Containing Protein (VCP) disease, announces a research collaboration with the National Center for Advancing Translational Sciences (NCATS) that will create organoid models derived from patient-specific cells to help identify the first disease-modifying drug for VCP patients.
“This project leverages cutting-edge technology to identify potential therapies that could dramatically improve the lives of VCP patients,” said Dr. Armelle Pindon, Cure VCP Disease Chief Scientific Officer. “By using patient-derived cells and a phenotypic screening approach, we can potentially develop drugs that directly address the underlying causes of the disease.”
The research, led by Marc Ferrer, PhD, NCATS' Director of 3-D Tissue Bioprinting Laboratory, proposes to produce engineer muscle tissue (EMT) models using VCP patient-derived iPSCs reprogrammed into myoblasts, from two different categories of patients, the most common mutations R155H inclusion body myopathy and the R159C, with muscle degeneration combined with Ataxia type-Purkinje cells degeneration and peripheral characteristics in the family history. They will investigate protocols that produce EMTs for healthy and VCP patients with different contraction patterns as phenotypic assays for drug screening. After a VCP disease vs healthy EMT phenotype is established, they will then screen a selected collection of compounds to identify potential drugs that reverse the disease VCP disease phenotype into a healthy one.
VCP, a Valosin-Containing Protein, is a AAA class of ATPase with a homo-hexameric functional structure. VCP function is involved in autophagy, protein clearance, mitochondrial function, lysosomal function, DNA repair, cell cycle regulation, retinal ganglion cell survival, gliosis, and innate immune system recruitment. VCP variants are at the origin of types of ALS, IBMPFD, CMT2Y, and other degenerative disorders. Modulating VCP interaction with mutated protein in various rare diseases has been shown to rescue pathological phenotypes (Ataxia type 3, ALS), and other rare neuro and muscular diseases could benefit from VCP modulators (NARP, Pearson Syndrome, Vacuolar tauopathies). A phenotypic screening approach using relevant 3D tissue models might be the ideal approach to identify the first therapeutical disease modifier for VCP patients.
If successful, further work might include the development of a VCP neuromuscular EMT model using VCP IPSCs reprogrammed myoblasts and motor neurons, and different techniques of neuromuscular junction stabilization will be tested and then characterized against the healthy counter model.
About the National Center for Advancing Translational Sciences (NCATS)
NCATS is a component of the National Institutes of Health (NIH) that builds knowledge and tools to accelerate the translation of scientific discoveries into new interventions that improve human health. NCATS conducts and supports research across the translational spectrum, focusing on the challenges of moving basic science findings into safe and effective treatments and devices for patients.
About Cure VCP Disease, Inc.
Cure VCP Disease, Inc., is a patient advocacy organization founded in 2018 to drive the development of a cure for diseases caused by mutations in the valosin-containing protein (VCP) gene, including muscle disease, bone disease, and the neurodegenerative diseases ALS, FTD, Parkinson’s, and CMT. Our mission is to build collaborations, fund research, and support patients within the global VCP community. We provide global education and awareness of VCP disease through conferences, educational webinars, and family support groups; facilitate a research network of over 70 scientists; and partner on research initiatives, including natural history studies, gene therapy, and drug discovery programs. Visit www.curevcp.org for more information.