Grant Awardees for 2006 Dystonia Research

Xandra Breakefield, PhD

Massachusetts General Hospital

Genetic Intervention Strategies for DYT1 Dystonia

To provide more insight into possible modes of therapeutic intervention in early onset torsion dystonia, these studies are aimed at resolving whether it is a better strategy to block expression of mutant torsinA or to provide an excess of the normal protein.

Pedro Gonzalez-Algre, MD

University of Iowa
The Torsin Family of Proteins and The Nuclear Envelope

TorsinA, the protein mutated in DYT1 dystonia, is one of four members of the torsin family of proteins. This study will examine the function of the other members of the torsin family of proteins to determine if they influence the function of torsinA and the neuronal dysfunction caused by torsinA when mutated in DYT1 dystonia.

Phyllis Hanson, MD, PhD

Washington University
A Candidate Substrate Binding Motif Torsin A: Design and Testing of an Inhibitory Peptide

Centered on the idea that torsinA is a chaperone-like enzyme that normally operates on proteins in the nuclear envelope, this project will design and test a peptide inhibitor to find out of inhibiting abnormal interaction of torsinA with its binding partners may be useful in developing targeted therapies for DYT1 dystonia.

Yuqing Li, PhD

University of Illinois at Urbana-Champaign
Dissecting the Functional Role of Torsin A in Midbrain Dopaminergic System

This research wil examine genetically-engineered mice that lack torsinA proteins in dopaminergic neurons to search for clues of how torsinA affects activies of these neurons that could ultimately lead to the symptoms in DYT1 dystonia.

Kevin McNaught, PhD

Mount Sinai School of Medicine
Brainstorm Pathology in DYT1 Dystonia

Using brain samples from DYT1 dystonia patients, this study will test the hypothesis that DYT1/torsinA causes nerve cell death or dysfunction in the brainstem, which is responsible for the symptoms seen in patients with the disorder.

Margaret Rice, PhD

New York University
Dopamine Release in DYT1 Transgenic Mice

Dopamine is a key neurotransmitter in motor systems. This study will examine mechanisms that underline altered dopamine release in mice that express the human protein that is mutated in early-onset dystonia. Ideally, this research will point to novel therapeutic approaches to treat human dystonia.

Michele Tagliati, MD

Mount Sinai School of Medicine
Low Frequency Deep Brain Stimulation for Treatment of Dystonia

A prospective, randomized clinical trial of Deep Brain Stimulation (DBS) will compare the effects of low and high stimulation frequency in patients with primary dystonia. This will help to establish more effective stimulation settings, which may provide enhanced therapeutic effects and extended battery life to minimize complications and costs associated with repeated replacements.

Ruth Walker, MD

Mount Sinai School of Medicine
Neurochemical Abnormalities in a Mouse Model of DYST1 Dystonia

Using a mouse model, detailed studies of chemicals in two regions of the brain most likely to be affected by dystonia will be explored. The goal is to obtain more information about how the mutation affects the brain and to help understand what might go wrong in humans with DYT1 gene mutation to cause dystonia.

Zhenyu Yue, PhD

Mount Sinai School of Medicine
Characterizations of BAC (Bacterial Artificial Chromosome) Transgenic Mouse Model for Dystonia

Using newly-developed genetic tools for study of human dystonia, this continues to investigate the primary neuron types, neuron circuits that are affected and responsible for disease onset and progression, and evaluate possible targets for drug intervention.