Grants and Contracts Details

Description

Evidence from clinical studies and preclinical animal models suggest the importance of neuroinflammation and proinflammatory cytokine overproduction from activated glia as a potential driving force for pathology progression in both acute neurodegenerative conditions such as traumatic brain injury (TBI) and chronic neurodegenerative disorders such as Alzheimer’s disease (AD). In addition, prior head injury is a known risk factor for later development of dementia, and it has been postulated that the chronic glial activation induced by TBI drives the enhanced susceptibility to later dementia. This raises the possibility that selective targeting of the dysregulated cytokine response, a component of the neuroinflammation that contributes to neuronal dysfunction, may be a useful therapeutic approach. Our candidate compound, MW01-6-189WH (hereafter called MW189), was developed as a selective suppressor of disease and injury-induced glia proinflammatory cytokine overproduction associated with destructive glia inflammation/neuron dysfunction cycles, and their long-term neurotoxic effects. MW189 has been shown to be efficacious in mouse models of TBI, intracerebral hemorrhage, and Alzheimer’s disease. MW189 has been through the entire preclinical drug development process, and the IND-enabling pharmacokinetic (PK) and toxicity studies revealed no significant liabilities. More importantly, MW189 has also successfully completed a first-in-man phase 1a single ascending dose (SAD) clinical trial with no safety issues. Because of the attractive features of the drug (aqueous soluble, stable, CNS-penetrant, drug-like properties) and its strong PK/safety profile in humans, we are very excited to move forward with further development. In order to move the development project forward, we are planning an application to the NINDS NeuroNEXT program for an exploratory clinical study that involves a phase 1b multiple ascending dose (MAD) study and a phase 2a proof-of-concept pilot human study in TBI subjects. Our NeuroNEXT clinical study concept has been selected to participate in the Network and move to the next steps of preparing a full application. This is very exciting news, because only a few proposals pass this first hurdle. However, we are now facing a time-sensitive problem. Specifically, a NINDS requirement for submitting the full NeuroNEXT application is that IND approval must be in place. The biotech company allowed the original IND to expire in 2013, and so we must resubmit for IND approval. Therefore, we are requesting from ADDF critical gap funding to support the regulatory costs associated with preparing and submitting the IND application for FDA approval, and drug costs to maintain the API and drug product under appropriate conditions and make new drug product if required by the FDA.
StatusFinished
Effective start/end date7/1/146/30/16

Funding

  • Alzheimers Drug Discovery Foundation: $209,364.00

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