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A Genetic Epidemiological study of young onset Parkinson's Disease in Ireland Dr. Tim Lynch B.Sc., FRCPI, MRCP (Lond), Consultant Neurologist, Mater Misericordiae and Beaumont Hospitals, Dublin - Principal Investigator Joseph Wiley MRCPI - Research Registrar Summary Parkinson's Disease (PD), a progressive neurodegenerative disorder, affects 5-6000 people in Ireland. It results in tremor, slowness, stiffness, poor balance and significant disability. Loss of dopamine producing nerve cells occurs within the brain stem. The best form of treatment is replacement of dopamine, this results in dramatic temporary improvement as shown in the movie Awakenings. Dopamine replacement is often only effective for five years and does not arrest the disorder. Why do dopamine producing nerve cells die off? This has been the holy grail of PD research for the last 30 years. Initial work suggested that environmental toxins were solely responsible for PD. Recent work supports the concept that both genetic and environmental factors are responsible for a cascade of events that lead to nerve cell death. Mutations in two genes, a-synuclein and Parken, result in Parkinsonism. The recognition that mutations in these genes can result in a loss of dopamine-producing nerve cells in parkinsonism resulted in a reappraisal of the causes of PD. It led to a deeper understanding of the mechanism of brain cell death and may result in preventative and restorative therapy. However, these mutations in these genes only account for a small percentage of the genes involved in PD. Studies of other families with PD is therefore of critical importance. Mutation in both genes result in loss of the dopamine producing brainstem cells in young onset Parkinson's disease (YOPD). Over 25% of patients develop PD before the age of 60. YOPD (onset before 60) commonly has a genetic cause. Therefore the YOPD population in Ireland is an ideal group to study the genetic contribution to PD. It is possible that studying this population in Ireland may result in the identification of new PD genes. A genetic epidemiological study of PD of a population has not been done. Such a study will provide critical scientific data of population demographics and genetics of PD. Ireland is an excellent site for such an important study because of its stable gene pool, large family units, relatively small size, and active PD support groups. In addition there are few neurologists or geriatricians allowing easier identification of YOPD patients. Methodology Patients with early-onset PD (before the age of 60) in Ireland will be identified. Drs Lynch and Wiley will contact the Parkinson's disease Association and PALS support groups to request they notify their members of the study. Drs Lynch and Wiley will present a number of presentations regarding PD to the Parkinson's support groups explaining the study. All concerns raised will be addressed. Any member interested in partaking will be contacted and assessed following notification of their general practitioner and specialist. In addition, all neurologists and geriatricians will be contacted requesting they complete and return an enclosed simple demographic form listing their patients with PD. Written informed consent from all patients involved in the study will be obtained emphasising this is a voluntary research study. The demographic, clinical and genetic data will be entered into a secure, confidential database. A small sample of blood will be drawn and DNA extracted, coded and stored in a secure -20 C freezer. The DNA will be labeled with a laboratory coded number. The key to the code will be kept in a secure computer. Mutations in a-synuclein and Parkin genes will be screened. When families are identified with three or more affecteds linkage analysis will be performed. Objectives Provide demographic and genetic information of YOPD in Ireland. It will identify the prevelance and incidence of YOPD. This is vital missing information for health planning. Also, we will identify the prevelance of mutations and a-synuclein and Parkin in the YOPD population. We may identify new PD genes. Funding Brain Research has allocated £53,000 in part-funding to this project which will be conducted over 3 years A Genetic Epidemiological study of young onset Parkinson's Disease in Ireland Dr. Tim Lynch B.Sc., FRCPI, MRCP (Lond), Consultant Neurologist, Mater Misericordiae and Beaumont Hospitals, Dublin - Principal Investigator Joseph Wiley MRCPI - Research Registrar Summary Parkinson's Disease (PD), a progressive neurodegenerative disorder, affects 5-6000 people in Ireland. It results in tremor, slowness, stiffness, poor balance and significant disability. Loss of dopamine producing nerve cells occurs within the brain stem. The best form of treatment is replacement of dopamine, this results in dramatic temporary improvement as shown in the movie Awakenings. Dopamine replacement is often only effective for five years and does not arrest the disorder. Why do dopamine producing nerve cells die off? This has been the holy grail of PD research for the last 30 years. Initial work suggested that environmental toxins were solely responsible for PD. Recent work supports the concept that both genetic and environmental factors are responsible for a cascade of events that lead to nerve cell death. Mutations in two genes, a-synuclein and Parken, result in Parkinsonism. The recognition that mutations in these genes can result in a loss of dopamine-producing nerve cells in parkinsonism resulted in a reappraisal of the causes of PD. It led to a deeper understanding of the mechanism of brain cell death and may result in preventative and restorative therapy. However, these mutations in these genes only account for a small percentage of the genes involved in PD. Studies of other families with PD is therefore of critical importance. Mutation in both genes result in loss of the dopamine producing brainstem cells in young onset Parkinson's disease (YOPD). Over 25% of patients develop PD before the age of 60. YOPD (onset before 60) commonly has a genetic cause. Therefore the YOPD population in Ireland is an ideal group to study the genetic contribution to PD. It is possible that studying this population in Ireland may result in the identification of new PD genes. A genetic epidemiological study of PD of a population has not been done. Such a study will provide critical scientific data of population demographics and genetics of PD. Ireland is an excellent site for such an important study because of its stable gene pool, large family units, relatively small size, and active PD support groups. In addition there are few neurologists or geriatricians allowing easier identification of YOPD patients. Methodology Patients with early-onset PD (before the age of 60) in Ireland will be identified. Drs Lynch and Wiley will contact the Parkinson's disease Association and PALS support groups to request they notify their members of the study. Drs Lynch and Wiley will present a number of presentations regarding PD to the Parkinson's support groups explaining the study. All concerns raised will be addressed. Any member interested in partaking will be contacted and assessed following notification of their general practitioner and specialist. In addition, all neurologists and geriatricians will be contacted requesting they complete and return an enclosed simple demographic form listing their patients with PD. Written informed consent from all patients involved in the study will be obtained emphasising this is a voluntary research study. The demographic, clinical and genetic data will be entered into a secure, confidential database. A small sample of blood will be drawn and DNA extracted, coded and stored in a secure -20 C freezer. The DNA will be labeled with a laboratory coded number. The key to the code will be kept in a secure computer. Mutations in a-synuclein and Parkin genes will be screened. When families are identified with three or more affecteds linkage analysis will be performed. Objectives Provide demographic and genetic information of YOPD in Ireland. It will identify the prevelance and incidence of YOPD. This is vital missing information for health planning. Also, we will identify the prevelance of mutations and a-synuclein and Parkin in the YOPD population. We may identify new PD genes. Funding Brain Research has allocated £53,000 in part-funding to this project which will be conducted over 3 years ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn