Download 2002-2003 - Parkinson Canada

Parkinson Society Canada
National Research Program
for 2002-2003 Cycle
Granting period
January 1, 2002 - December 31, 2003
OPERATING GRANTS
Researcher: Friedman Grant Grimes, D.A.
Name of Project: Parkinson's Genetics in a French-Canadian Population
Institution: Ottawa Hospital
Amount Year One: $30,280 (one year grant)
Amount Year Two: n/a
Total Awarded: $30,280 (one year grant)
Lay Summary: The cause of Parkinson's disease remains unknown. For several decades,
environmental factors were thought to be primarily responsible for causing the death of the cells that
produce dopamine. However, recently investigators from around the world have identified specific
changes in certain genes that cause the symptoms of Parkinson's in rare families. Currently,
mutations in three different genes (alpha-synuclein, parkin and ubiquitin C-terminal hydrolase) have
been identified and demonstrate the importance of genetic factors. I am interested in finding out how
genetic factors contribute to the cause of Parkinson's disease. In collaboration with Dr. D. Bulman at
the Ottawa Health Research Institute, we have been studying a large family where 13 individuals have
bee affected with Parkinson's disease. We are looking for a novel gene mutation in this family and
have narrowed down the area where the disease-causing gene is located. We are hopeful that we will
be able to identify the fourth disease-causing gene mutation in the very near future. This proposal is
directed at identifying the gene by collecting DNA samples from individuals who may harbour a similar
genetic mutation as the cause of their Parkinson's. Identifying genetic changes in these rare families
will provide important clues that will further our understanding of the possible mechanisms that cause
Parkinson's disease. Furthermore, understanding these mechanisms will ultimately result in a cure.
Researcher: Eldon Tanner/ Ruth Tanner Walker Doxey Grant Park, David S.
Name of Project: Role of CDK5 in an MPTP model of Parkinson's Disease
Institution: University of Ottawa
Amount Year One: $45,000
Amount Year Two: $45,000
Total Awarded: $90,000
Lay Summary: Parkinson's disease is a condition in which certain types of brain cells which make
the neurotransmitter dopamine degenerate. The biochemical mechanism by which this occurs is
unknown. We propose that one important activity which controls this process is a protein termed
Ddk5. By using a mouse model of Parkinson's disease, we proposed to examine whether an increase
in Cdk5 activity leads to and is required for the degeneration of neurons. By understanding this
process, we hope to develop new therapeutic strategies for the treatment of this disease.
Researcher: Dagher, Alain
Name of Project: The control of dopamine release studied by positron emission tomography and
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transcranial magnetic stimulation
Institution: Montreal Neurological Institute
Amount Year One: $45,000
Amount Year Two: $45,000
Total Awarded: $90,000
Lay Summary: Dopamine is a brain chemical that plays a role in the control of movement and
motivation. Neurons that make dopamine are damaged in Parkinson's disease, and the symptoms of
the disease are caused by dopamine lack. The main treatments for Parkinson's disease aim to restore
dopamine levels in the brain.
The current project will attempt to study how dopamine is released by brain cells. In particular, an
area of the brain called the cerebral cortex seems to play a role in regulating dopamine release. We
will use a technique called transcranial magnetic stimulation (TMS) to induce electrical activity in the
cortex. We will then measure the response of dopamine neurons to this electrical activity. To measure
dopamine release we will use positron emission tomography (PET), a type of brain scan that can
measure levels of dopamine inside the brain. We will compare healthy subjects to patients with
Parkinson's disease. We hope that this method will be useful in 1) understanding more about he
function of dopamine, and 2) eventually studying the efficacy of treatments aimed either at slowing the
progression of Parkinson's disease, as well as treatments such as transplantation of stem cells, that
aim to restore more natural levels of dopamine in the hope of better controlling the symptoms of the
disease.
Researcher: Sadikot, Abbas F. & Miller, Freda D.
Name of Project: Anterograde Transport of Neurotrophins in the Noradrenergic System Influences
Apoptosis of Midbrain Dopaminergic Neurons
Institution: Montreal Neurological Institute
Amount Year One: $45,000
Amount Year Two: $45,000
Total Awarded: $90,000
Lay Summary: Parkinson's disease is a movement disorder associated with aging, characterized by
progressive loss of nerve cells in a deep part of the brain called the midbrain. Cells in the midbrain
that are lost in Parkinson's disease use the chemical messenger dopamine. We are investigating the
factors that cause dopamine cells to die. Similar factors may cause loss of nerve cells in Parkinson's
disease and during normal development of the midbrain. We propose that a group of cells in a deep
part of the brain called the locus coeruleus produces a chemical messenger called brain derived
neurotrophic factor (BDNF), that protects against loss of dopamine cells. We will investigate whether
BDNF transported by the locus coeruleus to the midbrain has the ability to protect dopamine cells
either from death that occurs from normal development, or death that occurs in adults in response to
toxins. The experiments, which will be performed in mice, have direct relevance for human
Parkinson's disease. Since the locus coeruleus degenerates in human Parkinson's disease, we
theorize that the resulting loss of delivery of DNF to the midbrain makes dopamine cells more
susceptible to environmental toxins, and contributes to progressive dopamine cell loss.
Researcher: DiPaolo, Therese, Levesque, Daniel & Bedard, Paul
Name of Project: Ligand-activated transcription factors in levodopa-induced dyskinesias
Institution: Laval University Medical Centre (CHUL) and Laval University
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Amount Year One: $45,000
Amount Year Two: $45,000
Total Awarded: $90,000
Lay Summary: Levodopa therapy is the cornerstone of treatment of Parkinson's disease (PD).
However, this therapy is often associated with development of abnormal movements called
dyskinesias. These occur in between 30 and 80% of patients after chronic levodopa administration.
They develop progressively and become worse with time.
NGFI-B is a protein of the nuclear reception super family of transcription factors. Recent evidence
suggests a close relationship between NGFI-B and dopamine systems. Indeed, modulation of
dopamine transmission using agonists and antagonists dramatically influences NGFI-B expression.
Thus NGFI-B represents a previously unexplored protein that may participate in the intracellular
cascade of events induced by levodopa. We hypothesize that NGFI-B could play an important role in
development of levodopa-induced dyskinesias in PD.
The MPTP monkey is a well-characterized animal model of parkinsonism. We propose to compare
NGFI-B in brains of intact monkeys with those of saline-treated MPTP-monkeys and levodopa-treated
MPTP monkeys that developed dyskinesias. We will also investigate NGFI-B in human post-mortem
brains obtained from Dr. Ali Rajput from Saskatoon. These include controls and Parkinsonians with or
without dyskinesias.
Investigation of NGFI-B in PD will improve our understanding of the pathophysiology of the disease
and on the generation of side effects after levodopa therapy.
Researcher: Hutchison, William D.
Name of Project: Recordings of Movement-Related Neurons in Parkinsonian Patients During
Movement Disorders Surgery
Institution: Toronto Western Hospital
Amount Year One: $40,000
Amount Year Two: $43,000
Total Awarded: $83,000
Lay Summary: Recently, there have been new surgical options for patients with Parkinson's disease
(PD) that are poorly controlled with medication. Deep Brain stimulation (DBS) of the globus pallidus
and subthalamic nucleus are currently the main procedures that can restore normal function and ease
the burden of disease. During these surgeries we record the activity of individual brain cells in the
region in order to localize the target for placing the electrodes. We will examine the response
properties of neurons as the patient makes sequential movements of the hands to push buttons on a
board. They will be requested to memorize the sequence and press the buttons after a delay or simply
push the buttons one at a time as they light up. This task will give us an idea of where in the nucleus
the neurons are located that are responsible for automatic motor control, and provide specific details
on their function in the control of movements. The proposed studies will provide new knowledge about
the function and organization of these important motor nuclei and allow us to optimize our
neurosurgical procedures for PD.
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BASIC RESEARCH FELLOWSHIPS
Fellow: Hassani, Oum Kaltoum
Field of Training: Neurosciences
Institution: McGill University
Amount Year One: $45,000
Amount Year Two: $45,000
Total Awarded: $90,000
Fellow: Van Kampen, Jackalina M.
Field of Training: Neuroprotection & Neurogenesis in Parkinson's Disease
Institution: Dalhousie University
Amount Year One: $45,000
Amount Year Two: $45,000
Total Awarded: $90,000
Fellow: Scoggan, Kylie
Field of Training: Genetics of Parkinson's Disease
Institution: University of Ottawa
Amount Year One: $45,000
Amount Year Two: $45,000
Total Awarded: $90,000
Fellow: Postuma, Ron
Field of Training: Correlation of Clinical Course of PD with Genetic Causes of Parkinsonism
Institution: University of Toronto
Amount Year One: $45,000
Amount Year Two: $45,000
Total Awarded: $90,000
BOEHRINGER INGELHEIM CLINICAL MOVEMENT DISORDERS FELLOWSHIP
Fellow: Kraft, Scott
Field of Training: Pathogenesis of Motor Fluctuation and Genetics in PD
Institution: Movement Disorders Clinic, University of Calgary, Foothills Medical Centre
Amount Year One: $45,000
Amount Year Two: $45,000
Total Awarded: $90,000
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CLINICAL RESEARCH FELLOWSHIP
Wherrett Clinical Research Fellowship
Fellow: Huang, Zhigao
Field of Training: Pathogenesis of Motor Fluctuation and Genetics in PD
Institution: University of British Columbia
Amount Year One: $45,000
Amount Year Two: $45,000
Total Awarded: $90,000
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