SBIR-STTR Award

The mechanism of immobility osteopenia is a complex phenomenon of both biochemical and mechanical etiology. This study is designed to investigate the hypothesis that changes in patterns of both known and unknown small molecular weight compounds (e. g., tyrosine and tryptophan metabolites, neurotransmitters, cofactors, peptides and purines). This study can predict and precede or trigger changes in the balance of anabolic and catabolic processes ultimately resulting in osteopenia. The work will examine the osteopenia inducing human bedrest model as compared with seasonal bear metabolism as a model where osteopenia does not occur. Coulometric Electrode Array Systems (CEAS) will be used to isolate patterns of 4-500 compounds at the picogram level from plasma. Developmental software will be employed for complete pattern matching and data base transfer of 40-60 known and 200-300 unknown compounds. Existing plasma samples from 200-250 seasonal bear, 100-150 human bedrest study subjects, and 30-40 rats will be analyzed. Initial CEAS analysis of summer and winter bear plasma corroborates the theory that, fueled by the bear's winter lipid metabolism, protein synthesis proceeds at higher rates in winter than during summer. There were significant differences in serotonergic, kynurenic, dopaminergic, purine and peptide profiles. PaKern changes in small molecular weight nitrogen cycle metabolites may represent evolutionary adaptation coping with environmental factors and offering osteoregulatory mechanisms mitigating torpor's immobility effects. The data will be analyzed for inter and intraspecies differences in metabolic profiles that may be potential triggers or suppressors of osteopenia. Particular attention will be paid to acquiring information regarding the timing and pattern changes in anabolic metabolism. The data will guide design of a Phase II effort to investigate potential endogenous pharmaceuticals for suppression of osteopenia.Awardee's statement of the potential commercial applications of the research: The primary commercial application is a combined instrument, software and data analysis package utilizing automated chromatographic pattern matching capabilities, data base creation, and integrated statistical protocols for analysis of complex biological mixtures in the research, clinical, process, and quality control markets. Secondarily, the demonstration of the concept for description of endogenous compounds with pharmacological activity will allow penetration of a large coherent pharmaceutical industry market.National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The study uses human bed rest, a NASA space flight model, and the bear where Osteoenia does not occur, to demonstrate the potential of metabolic pattern analysis, based on Coulometric Electrod Array system (CEAS) technology in identifying process involved compounds. Our commercial goal is development of clinical market CEAS applications for degenerative disorders, and pharmaceutical market CEAS technology for rapid isolation of potential natural product drugs. In Phase I a complex CEAS method was developed to correlate ca. 600 plasma compounds among human bed rest and seasonal bear studies. The study defined ca. 45 significant differences in metabolic pathways and possible markers or regulating factors with potential relevance to the complex problem of osteopenia.Phase II has several goals:1) to extend the relevant compound data base to other disorders (spinal cord injury year 1);2) to isolate and identify significant unknown peaks that are potential markers or regulators;3) to evaluate the effectiveness of metabolic profile manipulation and/or specific compounds for Oppressing osteopenia in the NASA rat tail suspension model;4) to simplify specific compound CEAS assays for the clinical laboratory market;5) to configure CEAS technology for isolation of preparative quantities of compounds of pharmacological significance.National Institute on Aging (NIA)