Objectives and Projects of the Manganese Health Research Program
The objectives and strategy of the MHRP were devised by the Steering Committee in tandem with Dr. Michael Aschner, PI for the program.
The MHRP Steering Committee was chaired by Ms. Anne Tremblay, the Secretary General of the International Manganese Institute (IMnI), and its members included Dr. Barbara Beck of Gradient Corporation, Dr. Tomas Guilarte of the Johns Hopkins University, Dr. Steven Seilkop of SKS Consulting, Dr. Joan Cranmer of University of Arkansas, Dr. Leonard Levy, MRC Institute for Environment and Health University of Leicester, UK, Dr. Jerry Roper of Afton Chemicals, Mr. Christian Plazanet of Eramet, Mr. Jeff Leader of BHP Billiton, and Mr. John Hilbert of Kinghorn, Hilbert & Associates.
Building on the existing base at the time, the Steering Committee and Dr. Aschner focused their proposals on core projects deemed most relevant for the advancement of novel scientific knowledge that would characterize airborne and dietary manganese exposures, its deposition and fate, and its impact on central nervous system function.
The following were the MHRP objectives:
- define the scope of the contributions of environmental and occupational manganese exposure to health, disease and dysfunction;
- identify and investigate factors, such as age, nutritional deficiencies, pre-existing disease, and genetics, that make individuals more susceptible to the effects of manganese;
- develop common exposure assessment protocols and exposure reconstruction methodologies;
- determine whether manganese plays a role in increasing the relative risk for the development of idiopathic Parkinson’s disease (IPD) in welders;
- identify biomarkers for the diagnosis of the potential adverse effects of manganese, taking account of other factors such as diet (i.e. iron deficiency);
- understand the physiological mechanisms that govern manganese accumulation within the brain, with special emphasis on the role of olfactory transport of the metal;
- provide new modalities for the treatment of excessive manganese exposure (i.e. iron repletion);
- provide data to health forum regulators on which sound regulatory and risk assessment may be based;
- provide timely research activity awareness services to health professionals and the manganese industry and its workers;
- support innovative, multidisciplinary research, in humans and animal models, on the specific cellular, molecular, and physiologic mechanisms by which manganese mediates possible adverse health effects;
Six Research Cores along with one Support Core were established as Phase I of the MHRP:
Research Core 1 - Development of Guidance and Tools to Facilitate the Use of Routine Exposure Data in Future Epidemiology Studies of Manganese Exposed Workers, Robert Aitken, Core Principal Investigator (CPI);
Research Core 2 - Biomarkers of Early Onset of Manganese Neurotoxicities among Occupationally Exposed Chinese Workers, Wei Zheng, CPI;
Research Core 3 - Exposure to Welding Fume and Parkinson’s disease: Proposal for a Feasibility Study, Jounni Jaakkola, CPI;
Research Core 4 - Cellular Mechanisms Involved in the Uptake and Delivery of Inhaled Manganese via the Olfactory Nerve, David Dorman, CPI;
Research Core 5 - Magnetic Resonance Imaging (MRI) of Manganese Accumulation in the Rat Brain Associated with Iron-Deficiency and Supplementation, Michael Aschner, CPI;
Research Core 6 - Provision of Research Activity Awareness Services, Leonard Levy, CPI;
Support Core - Coordinator of the Mn Health Research Program Steering Committee and Administrator of the Research Activity Awareness Services, Anne Tremblay, CPI;
An additional 8 Research Cores were chosen for the MHRP Phase II:
Research Core 7 - Neurotoxicity after Pulmonary Exposure to Welding Fumes Containing Manganese, James Antonini, CPI;
Research Core 8 - Identification of Novel Biomarkers of Manganese Exposure, David Dorman, CPI;
Research Core 9 - A Study of the Nervous System in Welders, Dag Ellingsen, CPI;
Research Core 10 - Mechanisms of Manganese-Induced Damage at the Cell and Mitochondrial Level, Thomas Gunter, CPI;
Research Core 11 - Role of Manganese in Prion Disease Pathogenesis, Anumantha Kanthasamy, CPI;
Research Core 12 - Assessment of Genotoxicity and Carcinogenicity of Inorganic-forms of Manganese, Leonard Levy, CPI;
Research Core 13 - Role of Toxins and Genetics in Manganese-Induced DA degeneration, Richard Nass, CPI;
Research Core 14 - Molecular Mechanisms Underlying Mn Neurotoxicity, Jane Wu, CPI;
Acknowledgement: The Manganese Health Research Program is supported by US Army Medical Research and Material Command (USAMRMC) Award Number W81XWH-05-1-0239.