InteliSpark client, PK Biosciences Corporation, has been awarded a grant from the National Institute of Neurological Disorders and Stroke (NINDS) for their project, “Preclinical Evaluation of the Anti-Neuroinflammatory Properties and Pharmacokinetic Profile of a Novel Fyn Kinase Inhibitors”. This Phase I SBIR project will focus on developing a new class of disease-modifying drugs aimed at Parkinson’s disease (PD) treatment.
Current approaches to PD treatment mainly focus on alleviating symptoms, by compensating for neurochemical deficits. However, these treatments often fail to halt the progression of the neurodegenerative process. The lack of neuroprotective drugs for PD is attributed to a limited understanding of the complex mechanisms involved in the degenerative processes of the nigral dopaminergic system. Yet, recent discoveries regarding cell death pathways and oxidative stress signaling have offered some important clues that boost hope about the development of novel mechanism-based neuroprotective strategies for PD.
PK Biosciences has found that oxidative stress triggers the mitochondrially mediated caspase cascade and Fyn kinase activation to induce neuronal cell death, cell culture, and animal models of neurodegeneration. Furthermore, Fyn knockout mice were found resistant to MPTP-induced behavioral deficits, neurochemical depletion, and nigral dopaminergic neuronal damage. Additionally, PK Biosciences observed Fyn kinase is rapidly activated and mediates LPS= and SynPFF-induced increases in nitrite and proinflammatory cytokine production in cell culture and animal models of neuroinflammation. Together, these mechanistic studies demonstrate that Fyn is an essential upstream proapoptotic kinase involved in neuroinflammation, and as such, it could prove to be a promising therapeutic target for PD. With the grant assistance from the NINDS, PK Biosciences will continue work on their proof-of-concept study, to validate tri-heterocyclic small-molecule inhibitors of Fyn kinase as novel anti-neuroinflammatory agents for treating neurodegenerative disorders.