Investigating the Oligomerization of TorsinA as a Means to Develop DYT1 Dystonia Therapeutics
Abstract
Dystonia is a movement disorder than manifests itself in repetitive, involuntary muscle contractions, affecting parts (focal) or the entire (general) human body. A glutamate deletion (deltaE) in the enzyme TorsinA triggers the most common form of generalized dystonia, Toxins and traumatic brain injury can also trigger dystonia. The molecular mechanism of the disease is unclear. In this project we are examining the three-dimensional structure of TorsinA, particularly its filamentous form, and to develop drug candidates we are establishing assays to screen for effector molecules that will rescue the enzymatic activity of TorsinA deltaE. In this progress report we lay out the advances that have been made in the second year of the funding period. We have published the filamentous structure of TorsinA, which was our first specific Aim. We are now engaged in improving the resolution of the published structure. To develop the functional assays, we are in the process of establishing a procedure to produce milligram quantities of TorsinA at high purity. Further, we have developed a new cell-based assay for drug screening.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2020
- Accession Number
- AD1117747
Entities
People
- Thomas U. Schwartz
Organizations
- Massachusetts Institute of Technology