Methods for treating neurological conditions (WO2011159945)

Abstract

This patent application claims that inhibition of p21-activated kinases (PAK) reverses, partially reverses or delays clinical signs in neurological conditions (main claim for Huntington's disease (HD), substance abuse and addiction, Parkinson's disease, depression, bipolar disorder, anxiety disorder, posttraumatic stress disorder and neurofibromatosis). Several compounds with a pyrido-[2,3-d]pyrimidine-7(8H)-one core and high affinity to the catalytic domain of PAK1-4 are described in the patent. These PAK inhibitors are hypothesized to exert beneficial effects on clinical symptoms via modulation of dendritic spine morphology and/or synaptic function. Preliminary preclinical data suggest that PAK inhibition may be an interesting approach for the treatment of HD, neurofibromatosis and fragile X syndrome, while data for other neurological conditions are missing. Current limitations call for a comprehensive characterization of the role of PAK dysfunction in neurological disorders before further testing the effect of PAK inhibitors in relevant preclinical models. If ever, it will probably take many years before the most promising compounds will head to the clinic for further assessment in patients with neurological disorders.

Keywords::

• dendritic spine morphology
• Huntington's disease
• p21 kinase inhibition
• Parkinson's disease
• pyrido-[2,3-d]pyrimidine-7(8H)-one