The 2001/2002 Parkinson’s Unity Walk Funds Research Grants
On June 18, 2002 at the Parkinson's Unity Walk Thank You Reception held at City Hall in New York City, Chairman Martin Tuchman announced that the 2001/2002 Walk raised over one million dollars. Distribution of $755,000 was made to be spent on research. Of that amount, $200,000 went to the R21 Fast Track Grant Program for Parkinson's research and $555,000 was distributed to seven major Parkinson's disease foundations. Included in the $555,000 were funds from Team Parkinson at the Los Angeles Marathon. The seven organizations are: the American Parkinson’s Disease Foundation, the National Parkinson’s Foundation, the Parkinson’s Disease Foundation, the Parkinson Alliance, the Parkinson’s Institute, the Michael J. Fox Foundation for Parkinson’s Research.As mentioned above, the Unity Walk funded $200,000 into the R21 Research Grant Program. This Program, which awarded 35 two-year grants, is the largest initiative that the National Institutes of Health (NIH) has ever taken in the history of Parkinson's disease research. Its goal is to stimulate novel, or high impact approaches relevant to the cure, cause, prevention, or improved treatments of Parkinson's disease. On March 15, 2003, the first R21 Fast Track Grant Meeting took place in Washington, D.C. During the meeting, investigators shared their exciting preliminary data on Parkinson's disease research. This meeting was vitally important for the unity of Parkinson's organizations and our common goal of finding a cure to Parkinson's. For information on the meeting, researchers, and grants funded, visit: http://www.ninds.nih.gov/funding/neurodegeneration/r21_web_book.htm.
The following are grants being funded as a result of these distributions. We updated the grants with progress reports in early November 2003 and January 2004 when they were made available to us. We will share more updates, as they become available.
1. The American Parkinson Disease Association, Inc. is using its distribution to fund: High Frequency Stimulation of Subthalamus Evokes Long-term Depression of Excitatory Transmission in the Substantia Nigra Pars Reticulata.
This grant is being researched by Dr. Ke-Zhong Shen, MD. Ph.D.
Summary: The subthalamic nucleus has been shown to play an important role in regulating muscle tone and the dynamics of movement. This is of particular interest in studying Parkinson’s disease because research studies with animals has shown that deep brain stimulation of the subthalamic nucleus reverses the motor problems associated with Parkinson’s disease. This study intends to examine the underlying mechanism that results in the release of glutamate. The premise is to understand the cellular and molecular interactions for subthalamic nucleus induced long-term depression in the substantia nigra pars reticulate to better understand the actions of deep brain stimulation. This depression is not to be confused with psychological depression but rather refers to a decrease in specific substance in a specific part of the brain.
Progress Report update November 2003: Ke-Zhon Shen, MD, Ph.D.
Deep brain stimulation (DBS) has become a preferred choice for the treatment of advanced Parkinson’s disease (PD). The subthalamic nucleus (STN) is presently the most promising target for such stimulation. In this study, whole-cell patch clamp recordings were made from the STN in rat brain slices to investigate the effects of high-frequency stimulation (HFS) of the STN on membrane properties of, and excitatory synaptic transmission onto STN neurons HFS of the STN (at 100 Hz for 1 min) induced long-term depression (LTD) at glutamatergic synapses on STN neurons. This is the first demonstration of LTD induced by HFS. Induction of LTD will effectively reduce its excitatory influence on the output of the basal ganglia.
Furthermore, we found that HFS of the STN caused long-term reduction in membrane conductance of STN neurons, suggesting a direct inhibitory effect of HFS on STN neurons. This reduction in membrane conductance may be due to inactivation of some ion channels.
Presynaptic dopaminergic modulation of synaptic inputs to the STN was examined in unilateral 6-OHDA-lesioned rats. An increased sensitivity in dopamine-induced inhibition of GABA or glutamate release in the STN ipsilateral to the lesion of 6-OHDA lesions of mesencephalic dopaminergic neurons was found. These results suggest that endogenous dopamine acts on presynaptic receptors to modulate transmitter release to the STN, thereby to affect STN excitability. Our results also suggest that the STN may be an important target for levodopa therapy.
2. The Parkinson’s Institute using its distribution to help fund the CHANGSHOU Study.
This grant is being led by Caroline Tanner, MD, Ph.D. of The Parkinson’s Institute.
Summary: Many investigators believe that Parkinson’s disease, like most human disease, is the result of a complex interaction of inherited predisposing factors and non-inherited factors, such as lifestyle, exposure to chemicals, and possibly other factors. Studies focused on human populations with similar genetic make-up living in different locales enable researchers to examine environmental factors. Few such studies are done, however, because of the challenges of accessing such populations, ensuring identical protocols and identifying and analyzing the non-inherited factors. The Parkinson’s Institute has a remarkable opportunity to partner with Xuan Wu Hospital and the Capital Medical University Hospital in Beijing on a novel gene-environmental study, entitled the Chinese American Neurological and Geriatric Study of Health Outcomes (or Changshou—the Chinese word for longevity). The three institutions will take advantage of eight years of data on a cohort of aging Chinese residents in Beijing, China and continue to collect data on this group. Simultaneously, we will identify and study a comparable population of aging Chinese individuals in the San Francisco Bay area and a second comparison population from the areas of ancestral origin of these subjects. Changshou takes advantage of a brief “window in time.” China is changing rapidly. As it changes, there will no longer be the strong distinctions between our cohort population in the US and China. For example, the population we will study in China has a high percentage of individuals who reside in the same area all their lives, but mobility increases each year. The environment is also changing dramatically. If successful, these studies could provide fundamental insights in the environmental and genetic risk factors that underlie the cause of Parkinson’s disease. We also have a unique opportunity with this study: a grant from the Unity Walk to cover half the costs that will be matched by a Bay Area donor family.
Progress Report update November 2003
[Chinese American Neurological and Geriatric Study of Health Outcomes]
A. Specific aims. The long-term goals of Changshou project are to identify ways to promote healthy aging and to improve the functioning of older persons with brain disorders such as Parkinson’s disease and dementia. The primary aim of the Changshou pilot project is to develop feasible and efficient methods of ascertainment and recruitment of Chinese American residents in the San Francisco Bay Area aged 55 and older. The specific tasks of the project are:
1. To generate a representative list of Chinese Americans in the San Francisco Bay Area.
2. To determine the optimal ascertainment approaches by age, gender, place of birth, and immigrant generation. Two ascertainment approaches will be compared.
3. To determine the willingness of Chinese Americans in the Bay Area to volunteer in the proposed study and to collect reasons for refusal.
B. Implementation and progress. The Changshou study team has met monthly in face-to-face meetings to supervise the development and implementation of the project. To date, the following has been accomplished:
1. We developed a complete protocol including contact materials, and brochures.
2. Scripts for telephone contact were developed in English, translated into Chinese, and translated back into English by primary speakers of both Mandarin and Cantonese, in order to determine the appropriateness of the translations and to determine whether regional variations in language might influence comprehension.
3. We obtained formal IRB approval for the Parkinson’s Institute and for all collaborating institutions in December 2002.
4. We summarized 2000 census data for the five San Francisco Bay Area counties (Santa Clara, San Mateo, San Francisco, Marin, Alameda) to determine the age and gender distribution and density of Chinese elderly by census tract. This enabled us to identify our sampling frame in the targeted counties.
5. A proposal for identifying potential study subjects through the California Department of Motor Vehicles (DMV) was developed. To obtain a list of potential subject contacts from the California DMV, a comprehensive list of common Chinese surnames was generated from published lists. The surname list was submitted to the DMV together with a formal data request. The data release from the DMV is pending. The names of individuals meeting study criteria and residing within the selected census tracts of interest will provide one source of potential subjects. These subjects will be contacted directly, to determine eligibility and interest in the study. Random telephone dialing methods are a second approach being assessed for its value in identifying study subjects.
A protocol to identify potential study subjects is being developed. We have obtained electronic telephone listings and have recently purchased geocoding software. From these, we will generate phone “stems” (the first 5 numbers of a 7 digit telephone number) for the census tracts of interest. Telephone calls will be made using these phone stems, with random generation of the last 2 digits.
C. Plans. During the next year, the primary goal will be to determine the feasibility and efficiency of complete ascertainment of the elderly Chinese population within the targeted census tracts. Study interviewers fluent in English, Mandarin and Cantonese will be hired and trained in study procedures. Target phone numbers will be identified and contact with subjects will be initiated. The efficiency of ascertainment using two methods will be compared.
First, the utility of the DMV listing to obtain complete ascertainment within targeted census areas will be determined. All eligible subjects residing within the targeted census tracts will be identified from the DMV list. A second strategy for identifying subjects will use random digit dialing derived from the telephone stems (see B.5.) After the census-tract- specific phone stem is identified we will randomly generate target phone numbers and contact potential subjects.
Subjects will be asked to participate in a brief interview to determine eligibility and interest in participation in a larger study. Data analysis will compare the efficiency of the two ascertainments methods overall, and within specific census tracts. This planned work will provide the first step in developing a method to assemble a representative population of Chinese elders in the San Francisco Bay area, in order to determine risk factors for PD and other neurodegenerative disease and identify factors predictive of healthy brain aging.
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