PAK Program
Afraxis' lead program targets p21-activated kinase (PAK), a protein kinase that is a critical regulator of dendritic spine remodeling. Research from the MIT laboratory of Afraxis' scientific co-founder and Nobel Laureate, Dr. Susumu Tonegawa, demonstrated that abnormalities in FMR1 knockout mice, an animal model of Fragile X Syndrome, are reduced at both cellular and behavioral levels by inhibition of PAK. Postnatal expression of a dominant negative PAK transgene in the forebrain of FMR1 knockout mice resulted in improved dendritic spine shape, corrected the deficit in cortical synapse function, and improved several behavioral abnormalities, including those in locomotor activity, stereotypy, anxiety, and trace fear conditioning. These results suggest that pharmacological treatment of Fragile X patients with a PAK inhibitor may be possible - and represents the first disease-modifying approach for Fragile X.
Afraxis is developing proprietary PAK inhibitors to demonstrate clinical proof-of-concept in Fragile X, and is evaluating PAK inhibitors in a number of CNS disorders including schizophrenia and Alzheimer's disease. These PAK inhibitors have the potential to address large unmet medical needs with disease-modifying drugs that directly target the key underlying cellular pathology behind CNS disorders.
As the first company to target modulators of dendritic spines for the treatment of CNS diseases, Afraxis is establishing an expansive intellectual property portfolio. Patents include PAK inhibitor composition of matter applications - as well as methods to treat patients suffering from a disease resulting from dysfunctional dendritic spines.
