Afraxis will partner with the NIH under its Therapeutics for Rare and Neglected Disease (TRND) program to further development of its preclinical candidates for fragile X syndrome. The company is developing drugs to treat rare genetic diseases through the modulation of p21-activated kinase (PAK).
This protein kinase 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. Afraxis is developing PAK inhibitors to demonstrate clinical proof-of-concept in fragile X as well as a number of CNS disorders including schizophrenia and Alzheimer disease.
"TRND collaborations help companies focusing on rare and neglected diseases overcome one of the biggest obstacles facing all drug development companies: advancing programs through that 'valley of death' between identification of a promising compound and clinical-stage development when a program becomes more attractive to a big pharma partner," points out Jay Lichter, Ph.D., president and CEO of Afraxis.
"This is a tremendous opportunity for Afraxis as the NIH is providing access to state-of-the-art laboratory facilities, the expertise of collaborating NIH scientists, and the financial resources to continue our research and development efforts through the initiation of human clinical trials."
To make a potential compound attractive to private partners in order to get a treatment to patients, TRND advances a compound through the drug development process to the point where it can be tested in humans. TRND provides all aspects of preclinical development needed to turn promising compounds into potential medicines ready for clinical evaluation. It is anticipated that the average TRND project will take approximately three years.
NIH has allocated $50 million to support R&D collaborations between NIH and TRND partner companies in 2011. More than 60 companies submitted proposals to the NIH, and four were selected to participate in TRND.