Promising Outcomes of Original Grant:
The goals of the original grant were to expand the number of PD patients enrolled, incorporate new questionnaires for recording non-motor manifestations of PD, assess the potential of skin and olfactory bulb as biopsy sites for diagnosing PD, test current pathological staging systems for PD and survey the spinal cord and peripheral nervous system for the distribution of Lewy body-related pathology. These goals were accomplished with especially promising outcomes being the first detailed description of mild cognitive impairment in PD, the identification of incidental Lewy body disease as a probable preclinical stage of PD, development of statistical models for the development of PD and for dementia in PD, publication of an improved pathological staging system for PD and the first detailed mapping of Lewy body-related pathology in the spinal cord and peripheral nervous system.
Objectives for Supplemental Investigation:
With the supplemental grant the goals are to further increase enrollment of PD subjects, improve the database so that external investigators will be able to access clinical and neuropathological data, further refine statistical models for the development of PD or cognitive decline in PD, expand tissue-based collaborative investigations with external investigators and test the hypothesis that post-translational alpha-synuclein modifications occur at an early stage of PD pathogenesis. This series of investigations will thus expand on what was achieved in the original project, test an important molecular hypothesis and greatly accelerate studies of the Brain and Body Donation Program population by incorporating several new projects led by external investigators that were awarded grants for this purpose through a concurrent MJFF initiative, Clinicopathological Correlations of Parkinson’s Disease.
Importance of This Research for the Development of a New PD Therapy:
The Brain and Body Donation Program provides a unique resource for heretofore unperformed longitudinal clinicopathological studies of the steps leading to PD and dementia in PD. These studies will ultimately provide a detailed clinical and molecular flowchart of the critical pathways, with the twin goals being to: 1) Identify clinical or laboratory-based biomarkers that will identify subjects at increased risk. 2) Identify early molecular changes that are amenable to therapeutic intervention. Achievement of these goals will result in greatly more efficient selection of subjects entering clinical trials and in new molecular therapies directed at early disease steps.