2013 Annual Research Grants

  • Jose Miguel Bras, PhD
  • University College, Institute of Neurology
  • London, England

 

A Role for the de Novo Mutations in Parkinson's Disease

  • Great advances have been made in discovering genetic events that lead to Parkinson's disease. This study will identify new genes that cause this devastating disease, helping to understand how the disorder starts and possibly leading to improved therapeutic approaches to slowing or even stopping the development of the disease.

 

  • Edward Burton, MD, DPhil, MRCP(UK)
  • University of Pittsburgh
  • Pittsburgh, Pennsylvania

 

Generation of Torsin 1 Knockout Zebrafish

  • The most common genetic form of dystonia, DYT1 dystonia is caused by a change in a gene that carries the instructions necessary for brain cells to make a protein called torsin. Using the zebrafish that makes a protein very similar to human torsin, this research will use the torsin knockout model to determine what torsin does in the brain, and to understand how this goes wrong in DYT1 dystonia. The ultimate goal is to develop new drug treatments for dystonia.

 

  • Mark Edwards, PhD, MRCP(UK)
  • University College, Institute of Neurology
  • London, England

 

rTMS for the Treatment of Musician's Dystonia

  • Musician's dystonia causes involuntary posturing of the affected hand. It has been suggested that involuntary movements develop because inappropriate motor memories that incorporate unwanted actions are formed during music practice under conditions of high anxiety and stress. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique which has been shown to influence motor memory retention/consolidation. This study will explore whether rTMS given to patients during active performance of movements that induce dystonia can reduce or abolish the "motor memory" responsible for the abnormal hand posturing.

 

  • Alfred Goldberg, PhD
  • Harvard Medical School
  • Cambridge, Massachusetts

 

Role of Nedd4 Activity in Protection Against Alpha-synuclein Accumulation and Parkinson's Disease

  • Studies have established that the build up of a-synuclein in dopaminergic neurons is a critical contributor in the development of Parkinson's disease. Research indicates that Nedd4 modifies a-synuclein content and its toxicity. This work will test whether it may be possible to enhance Nedd4 activation as a possible therapeutic approach to slow or prevent Parkinson's disease progression in neurons. Such experiments could provide a strong rationale for searching for drugs that bind to this domain and prevent to accumulation of a-synuclein.

 

  • Henry Houlden, PhD, MRCP(UK)
  • University College, Institute of Neurology
  • London, England

 

Neuodegeneration with Brain Iron Accumulation (NBIA): Gene Discovery and Characterization

  • Neurodegeneration with brain iron accumulation (NBIA) refers to a group of inherited neurodegenerative diseases characterized by progressive, severe dystonia, parkinsonism. This project seeks to identify and characterize novel genetic causes of NBIA using a set of powerful, complementary genetic techniques. The goal is to accelerate understanding of dystonia at the molecular level and to pave the way for the development of new treatments.

 

  • Rachel Saunders-Pullman, MD, MPH**
  • Beth Israel Medial Center
  • New York, New York

 

Phenolypic Spectrum of GNAL and THAP1 Mutation Dystonia

  • For those with a known genetic etiology, such as dystonia due to DYT1 and DYT6 mutations, information about treatment response, genetic counseling information have been studied. However, in the case of DYT6, the range of features associated with mutations is not well understood. This project will address the clinical features associated with this mutation and hopefully will lead to a better understanding and treatment for dystonia, and will also guide research in understanding the basic mechanisms and developing a cure for this form of dystonia.

 

  • Terrence J. Sejnowski, PhD
  • University of California, San Diego
  • San Diego, California

 

Objective Quantification of Phenotypic Expression in Cranial Dystonia

  • The goal of this study is to evaluate computer-aided video processing of facial muscle activity in cranial dystonia. Although clinicians have become adept at treating cranial dystonia, objective measures of symptom severity and frequency have lagged behind. Ultimately, it is hypothesized that advances in video-processing software can be used for assessing more broadly defined facial dyskinesias, and its spatiotemporal resolution will also facilitate linking pathological patterns of muscle activity to underlying pathophysiology.

 

  • Philip Starr, MD, PhD*
  • University of California, San Francisco
  • San Francisco, California

 

Cordial Phase-Amplitude Couling in Patients with Generalized Dystonia

  • The aim of this work is to understand cortical function in dystonia by studying patients undergoing awake neurosurgery. This study will investigate the cordial activity of patients with generalized dystonia. Deep brain stimulation (DB) is an efficient therapeutic treatment for movement disorders during which brain structures are stimulated electrically to alter the brain activity causing abnormal movement. To improve and develop safer and simpler therapeutic strategies, it is important to better understand the pathophysiology of dystonia, especially at the cordial level.

 

  • Peter Vangheluwe, PhD** (funded through The Michael J. Fox Foundation)
  • KU Leuven
  • Leuven, Belgium

 

Functional Characterization of ATP13A2, a P-Type Transport ATPase

  • The discovery of several genetic risk factors and progress on their cell-biological role significantly impact understanding of Parkinson's disease. Strong genetic evidence indicates that mutations in ATP13A2 in Parkinson's disease susceptibility locus lead to the Kufor-Rakeb syndrome (KRS), a severe early-onset autosomal recessive form of Parkinson's disease with dementia. However, the molecular properties of ATP13A2 remain unexplored. Uncovering its cell-biological function and role in neurodegeneration and dementia require the identification of the transported substrate. Transporters are implicated in a variety of human disorders and often, these are considered potential drug targets.

 

  • Nicholas Wood, PhD, **MRCP(UK)
  • University College, Institute of Neurology
  • London, England

 

Using Genetic to Understand Dystonia: Characterization of Effect of Mutations in AN03 and Exome Sequencing in Familial Dystonia

  • Exome sequencing is a relatively new technique that involves reading the most important parts of an individual's genetic code all in one go. Using this technique to identify mutations in the novel gene, ANO3, as the cause of a subset of cases of focal dystonia, the work will investigate the means by which mutations in this gene might lead to dysfunction at the cellular level, and how such dysfunction could be linked to the development of the abnormal movements seen in dystonia.

 

* The Dorothy Feiss Scientific Research Grant

** Jake’s Ride for Dystonia Research Grant