Through the generous support of its corporate sponsors, 100% of all donations made to the Parkinson's Unity Walk are distributed among the major U.S. Parkinson's disease foundations for Parkinson's disease research. The foundations include: (1) American Parkinson Disease Association; (2) the National Parkinson's Foundation; (3) the Parkinson's Action Network; (4) the Parkinson's Disease Foundation; (5) the Michael J. Fox Foundation for Parkinson's Research; (6) The Parkinson Alliance; and (7) the Parkinson's Institute.
We are excited to share with you information about the following grants —all of which are made possible from 2005 Parkinson's Unity Walk distributions. We will update the grants with progress reports as they are made available to us. To read about grants we funded as a result of past Unity Walks, please visit our 2004 Grants Page, our 2003 Grants Page, and our 2001/2002 Grants Page. We are also happy to share progress reports on each as they become available.
1. The American Parkinson Disease Associations is using its distribution to fund:
Investigator No. 1: Cyrus P. Zabetian, MD, MS
Location: Geriatric Research Education and Clinical Center VA Puget Sound Health Care System, Seattle, WA
Title of Study: A Comprehensive Screen of the LRRK2 Gene in Familial Parkinson’s Disease and Dementia with Lewy Bodies
Purpose of Study: To perform a comprehensive mutational analysis of the LRRK2 gene by resequencing the entire coding region and all intron/exon junctions in 50 subjects with familial Parkinson’s disease (PD) and 20 subjects with familial dementia with Lewy bodies (DLB). To determine whether newly discovered mutations segregate with disease by genotyping all available family members in each mutation-positive pedigree. To estimate the frequency of any newly discovered putative pathogenic mutations in a large sample of sporadic PD (n=400), DLB (n=200) case, and controls (n=600).
Investigator No. 1: Eunsung Junn, Ph.D.
Location: UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ
Title of Study: Effects of DJ-1 and Daxx interaction on Cell Death
Purpose of Study: To determine the role of DJ-1 in the Daxx/ASK1-mediated cell death. Daxx is known to interact with ASK1, causing its activation which subsequently promotes cell death. The role of DJ-1 will be assessed in this context in dopaminergic cells, especially regarding its ability to block cell death and ASK1 activation as well as to regulate Daxx localization. To test if the Daxx/ASK1 pathway is indeed involved in the pathogenesis of a PD model, MPP+ will be employed as a cell death inducer. If the Daxx/ASK1 pathway is activated in this model, and if DJ-1 can block cell death, ASK1 activation and Daxx location induced by MPP+ will be studied.
Reporting procedure: Activity reports will be required before the second (6 month) and third (12 months) payments are made.
2. The National Parkinson Foundation is using its distribution to fund the following:
Grant Awarded to: Vincenzo Bonifati, M.D., Ph.D, Erasmus Medical Center, Rotterdam Department of Clinical Genetics
Project title: Genetic Determinants of Early-Onset Parkinson’s Disease
By unraveling the genetic defects causing rare forms of PD, the researchers expect to understand better and faster the mechanisms underlying the common, non-hereditary forms of the disease. The researchers aim to analyze the DNA (genetic code) from many patients with PD and their relatives in order to identify novel genes defective in this disease. They believe that this strategy will ultimately open novel avenues for curing and preventing PD.
Grant awarded to: Jonathan Sebat, Ph.D, Cold Spring Laboratory
Project Title: Determining Genetic Causes of Parkinson’s Disease by ROMA
ROMA is a DNA microarray chip methodology that enables the researchers to scan the entire genome at high resolution and to identify the disease-causing mutations directly, greatly accelerating the process of identifying disease genes. The initial efforts in the use of ROMA to study a neurological genetic disorder have proven successful. By scanning the genomes of 80 patients with autism, the researchers succeeded in identifying mutation in several disease-causing genes. This project will be a pilot study to analyze the DNA of 100 patients diagnosed with Parkinson’s disease by ROMA in order to find gene copy number polymorphisms specifically associated with Parkinson’s disease (PD), and to identify candidate PD genes in these regions.
3. Parkinson's Action Network (PAN), founded in 1991, is the unified education and advocacy voice of the Parkinson's community, fighting for a cure. Through education and interaction with the Parkinson's community, scientists, lawmakers, opinion leaders, and the public at large, PAN works to increase awareness about Parkinson's disease and advocates for increased federal support for Parkinson's research.
PAN also provides the information and resources necessary to empower people with Parkinson's disease to act on their own behalf and gain a greater sense of control over their health and their future. For more information on PAN, please see its website at www.parkinsonsaction.org.
4. Parkinson’s Disease Foundation is using its distribution to fund the following:
Investigator: Dr. Ying Tan
Project Title: Interaction between PD and Nrdp1 in drosophila models
Parkin is a gene that was very early discovered to, when deficient cause familial parkinsonism of the young-onset of “juvenile” type. It too, is autosomal-recessive, thought to be a “loss-of-function” PROBLEM. Since drosophila (fruit fly) models are now available, many scientists are using these models to investigate genetic functions (they are easily bred and inexpensive). Dr. Ying Tan at the University of Massachusetts (Worcester) will use his funds to generate yet another drosophila model that overproduces a protein called Nrdp 1 that destabilizes the production of parkin in cultured animal cells. His hypothesis is that this protein may modify the features observed in the model with either elevated or reduced levels of the parkin protein. He and his colleagues will also cross these models with those over-and under-expressing other proteins such as alpha-synuclein in an attempt to determine how multiple modifications can affect the molecular pathogenesis of human Parkinson’s disease.
Investigator: Dr. Nicholas Hallworth
Project Title: Mechanisms Underlying Pathological Rhythmic Burst Firing in Subthalamic Nucleus Neurons Following Dopamine Dennervation
Over the nearly twenty years of studying the use of deep-brain stimulation for symptomatic control of PD symptoms, most surgeons agree that regulating the subthalamic nucleus in this manner provides the best relief. This brain area’s irregularity seems to be caused by the degeneration of mid brain dopaminergic (DA) neurons. Dr. Nicholas Hallworth will use his PDF funds to continue working with his mentor. Dr. Mark Bevan, at Northwester University (Chicago). He will compare electrical activities of brain tissue obtained from healthy animals with that of reserpinized (lesioned) mice, in an attempt to clarify both the mechanism(s) underlying and the site of origin of the abnormal activity within the brain. He concluded that his study’s results could contribute to the refinement of high-frequency stimulation procedures and may provide a foundation for the rational development of even better symptomatic treatments.
Investigator: Dr. Mihaela A. Stavarache
Project Title: In vivo silencing of PINK1 expression using Adeno-Associate Virus vectors
Yet another gene responsible for a hereditary form of early-onset parkinsonism is PINK 1 (PTEN-induced putative kinase 1). It is known to be an autosomal recessive mutation. This suggests that the problem is caused by a loss of function rather than an overdose of genetic material. Dr. Mihaela S.A. Stavarache will continue her post-doctoral work at Weill Medical College (Cornell University, New York) using a genetic technique known as RNA interface (RNAi) that shuts down or “silences” a disease gene while leaving others untouched. An adeno-associated virus of the type used in inserting, for example, growth factors into a laboratory animal will be used to take the RNAi molecule into the brains of rodents so that the gene’s function can be studied in the dopamine-producing neurons of the substantia nigra, a brain area affected in classic Parkinson’s disease. Dr. Stavarache and her colleagues hope to prove that loss of PINK 1 can cause neuronal death and that the obverse, or over expression of the gene, might protect nigral dopaminergic neurons during life. As with all of the genetic studies ongoing, the goal of this study is to learn the mechanisms of the classic disease that, to date, remain unknown.
5. The Michael J. Fox Foundation for Parkinson's Research will use its grant toward the Community Fast Track initiative and Biomarkers II program.
Under the Community Fast Track initiative, researchers are invited to submit investigator-initiated grant application to conduct new, novel or innovative research relevant to the cure, cause, prevention, or improved treatment of PD and its complications. Biomarkers II is a two-year research program designed to accelerate the development and validation of a biomarker of Parkinson’s disease. For more information see its website at website at www.michaeljfox.org.
6. The Parkinson Alliance is committed to funding the most promising and scientifically validated Parkinson's disease research that will help find the cure to Parkinson's. Funding from the Parkinson's Unity Walk helped finance the Michael J. Fox Foundation for Parkinson's Research "Community Fast Track." The annual program seeks out proposals that represent a new approach or new concept, and have the potential to significantly advance the field of Parkinson's research.
In addition, the funds from the Parkinson's Unity Walk will support 16 specific research grants. Selection of a grant is on the basis of scientific merit of the project. This is determined by scientific advisory boards of the major Parkinson's foundations. For more information please visit its website at www.parkinsonalliance.org.
7. The Parkinson’s Institute is using its distribution to fund the following:
Project Title: The cause and consequence of abnormal a-synuclein aggregation
Principal Investigator: Seung-Jae Lee
Deposition of amyloid-like fibrillar protein aggregates is a common pathological feature of many human neurodegenerative diseases, including Parkinson's disease (PD). While the direct role of these fibrillar inclusion bodies in disease progression is the subject of intense debate, it has become evident during recent years that protein conformational defects that lead to fibrillation are an integral part of the pathogenic mechanism. Therefore, understanding the molecular mechanisms underlying protein misfolding and aggregation might hold the key to unraveling common pathogenic mechanisms for these devastating neurologic disorders. One of the main goals of my research group is to elucidate the pathophysiological function of a-synuclein, a neuronal protein that is implicated in several human neurodegenerative diseases, including PD, dementia with Lewy bodies, and multiple system atrophy. The objective of the current project is to understand the cause and consequence of abnormal a-synuclein aggregation at the molecular and cellular levels and to use this information to further understanding of the pathogenesis of PD. Knowledge we obtain from this study will eventually lead to the development of new strategies that are designed to prevent the progression of a-synuclein pathology, something which would be most welcome in the current research climate where new strategies for neuroprotection are being searched for intensively.