The scientific research proposed, the determination of pre-clinical stability, pharmacokinetics and toxicology testing of Maas BiolAB's proprietary cyclosporin intrathecal formulation, Mitogard(tm), will allow the company to file for Investigational New Drug (IND) approval with the Food and Drug Administration (FDA) and begin human clinical trials for amyotrophic lateral sclerosis (ALS). Mitogard(tm) is designed for delivery into the intrathecal space. Cyclosporin does not readily cross the blood brain barrier, thus intrathecal delivery is needed to reach affected areas of the brain and spinal cord. Though cyclosporin is an FDA approved active ingredient and its safety profile is known to the FDA, both the Mitogard(tm) formulation and proposed intrathecal route of administration are new requiring further stability and toxicology studies. Cyclosporin is a powerful neuroprotectant, separate from its traditional role as an immunosuppressant, and has shown efficacy in pre-clinical models of ALS, making it a promising candidate to reduce the burden of the disease and extend the life of ALS patients. GMP stability data will be gathered over two years, toward confirmation of product shelf life. SBIR Phase I (year one) testing will confirm the purity and concentration of cyclosporin in the formulation and stability will be measured up to 12 months (with up to 24 month measurements in Phase II of the fast-track proposal). Potency testing will be performed using a HPLC assay following the chromatography guidelines of the USP NF monograph on injectable cyclosporin. Rodent and sheep toxicology tests will ensure that Mitogard(tm) can be safely administered intrathecally. Maas BiolAB and Northern Biomedical Research have planned dose escalation studies via lumbar puncture in both the rodent and sheep to determine the maximal and optimal safe dosing ranges of Mitogard(tm), and will include the histology of the spinal cord and brain. These will be followed by GLP 28 day rodent and 90 day sheep continuous pump infusion studies. These toxicology studies will provide data to enable an IND first for lumbar bolus injection into the intrathecal space, followed by a second IND for continuous infusion via implanted drug delivery pump. Progression from first lumbar puncture to second pump delivery safety studies will satisfy FDA requirements of drug delivery progression. This translational research will bring cyclosporin, which is a powerful broad-spectrum neuroprotectant drug in animal models, from animal testing to approval for human clinical trials. If cyclosporin is found to be an effective neuroprotectant in humans, it could reduce suffering from amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). This research will allow the FDA to assess the safety and stability of cyclosporin in treating ALS and to give permission to start the first human ALS trials.
