Neurotoxin Exposure Treatment (Parkinson’s) Research: NETPR
The Neurotoxin Exposure Treatment (Parkinson’s) Research, NETPR, portfolio is dedicated to advancing solutions to the understanding and intervention in mechanisms underlying the development of Parkinson’s disease and Parkinsonian conditions. Funded projects are required to address “dual use” needs of the portfolio in that developments of the portfolio are also intended to address risk factors for performance decrements in service men and women and develop solutions relevant to identification, remediation, or reversal of such risks in operational and deployment environments. The portfolio uses an iterative, problem-solving approach in which funded projects have well-supported preliminary evidence, clear hypotheses and metrics and include specific means of validating findings.
The diagram highlights NETPR's focus on correlation of genetic and environmental impacts on cellular function and
identification of biomarkers, vulnerable populations, and cellular targets for therapeutic interventions.
Projects are submitted for consideration for funding through the USAMRMC Broad Agency Announcement and specific solicitations. They must meet the developing goals of the portfolio. Current areas of interest/focus include: epigenetic mechanisms associated with development of Parkinson’s in familial and sporadic PD; stable epigenetic modifications associated with organophosphate/ organochlorine correlated PD; dopaminergic Substantia nigral, ventral tegmental and striatal cellular mechanisms altered during local inflammatory processes; influence of non-dopaminergic neural transmission associated with development of non-motor signs in PD; PD associated imaging and molecular alterations of the hippocampus; molecular mechanisms affected by exercise in progression of PD. Proposal request is likely to be restricted to one to two year pilot projects with upper limits (to include both direct and indirect costs) of $300,000.00 per year.
Specific requirements will be published with the request for proposals. Investigators should examine proposal requests published at http://www.grants.gov for announcement of such requests. Announcements will also be published on the TATRC web page when released through grants.gov.
The program is managed as a dual-use program. It advances understanding of Parkinson’s Disease (PD) progression and develops means of diagnosis, prevention, and therapeutic intervention for both dopamine and non-dopamine responsive symptoms, thereby enhancing strategies for treatment of motor and non-motor conditions that affect quality of life and performance for PD patients. For military service members, the research outcomes are leveraged to support long-term health and performance through an increased understanding of biologic mechanisms underlying potentially harmful military exposures, development of information on the safety of chemicals and drugs used in military operations, means of measuring environmental impacts on performance, and improvements in materiel design to reduce potential risks of military exposures.
Key tenets supporting portfolios advance are that alterations in any neurotransmitter system must impose compensatory alterations in other physiologic systems and that the motor aspects—the prime clinical diagnostic criteria of PD—are the result of convergent alterations, which are themselves the result of varied initiating vulnerabilities within the affected population. The inherent limitations of individual genetic inheritance, with an array of combinatorial effects consistent with requirements for biologic differentiation, provides diverse opportunities for environmental modulation and presentation of diverse dysfunctional clinical manifestations in the heterogeneous population. The program’s focus (determination of neurodegenerative mechanisms and related compensatory effects that compromise motor, autonomic and cognitive systems) clarifies why damage to these systems, which are characteristic of the disease in Parkinson’s patients, also provides information relevant for potential performance and health risks for military personnel from similar operational exposures.
As the risk factors for PD, noted in epidemiological research, include many of the hazards in operational environments (e.g., organophosphates, organochlorine compounds, head trauma, certain solvents, etc.), research in the portfolio provides a basis for developing spin-offs that enhance the safety and well being of military service members. The improved understanding of the pathnophysiology of neurodegenerative changes provides a basis for identifying associated risks of military hazards and development of preventive strategies and treatments which, in turn, suggest additional areas for research that can be exploited to clarify the natural progression of PD.
A Sampling of NETPR Credited Publications:
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To learn more about Neurotoxin Exposure Treatment (Parkinson’s) Research (NETRP) or the Telemedicine & Advanced Technology Research Center (TATRC) contact us at: