Developing Novel Medicines to Treat Dystonia
Abstract
Dystonia is a movement disorder characterized by sustained involuntary postures and/or slow twisting movements. Dystonia is an unremitting and poorly treatable movement disorder that causes pain and motor disability. Dystonia can arise in many contexts limb trauma, traumatic brain injury, stroke, neurodegenerative diseases, antipsychotic medication use, inherited syndromes, and sporadically. Military personnel are at increased risk to develop dystonia because of exposure to risk factors such as limb trauma, traumatic brain injury, repetitive use tasks, and certain medications. Unfortunately, both the number of treatment options for dystonia and their efficacy are severely limited. Moreover, no disease-modifying options exist; all current treatments are symptomatic. To discover new drug treatments for dystonia, we developed a robust, cell-based, high-throughput assay to monitor dystonia-related cell pathology and screened >40,000 compounds. Here we will advance the most promising candidates through medicinal chemistry optimization to develop compounds with suitable drug-like properties. Drug-like molecules will be further characterized for their activity in neuronal dystonia models from mice and humans. Lastly, using the knowledge gained during the medicinal chemistry phase, modified molecules will be made in order to capture the binding partner of the drug and identify the target protein through which the drug exerts its beneficial effects. The outcome of this effort will be to generate first-of-kind drugs that can be used for testing in preclinical animal models and ultimately human studies. The activities herein will also generate a comprehensive surrounding data package in order to attract commercial partners. Success in this effort has the potential to generate affordable novel dystonia drugs that can overcome the significant limitations of the current therapy options for this chronic disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2022
- Accession Number
- AD1186441
Entities
People
- Matthew D. Hall
- Nicole Calakos
- Samarjit Patnaik
- Vinoth Chenniappan
- Zachary F. Caffall
Organizations
- Duke University