CALIFIA BIO
NIH extends grant funding for NeuroAids URMC / Califia Bio Collaboration for five additional years: The research team lead by Harris A. “Handy” Gelbard” at the University of Rochester Medical Center has successfully renewed the third cycle of a multiple year program grant (3PO1MH64570) to continue research for the discovery of potential treatments of HIV–associated neurocognitive disorder (HAND). The NIH has recently announced $ 6.7 million in new funding for this project. This funding covers work in Dr. Gelbard’s laboratory as well as in Dr. Stephen Dewhurst’s laboratory at URMC and for Howard Gendelman at the University of Nebraska who will evaluate compounds in novel animal models of HAND.
Califia Bio has identified a lead series of kinase ihibitors with unsurpassed ability to penetrate the blood brain barrier and a potential development compound has been identified. This compound achieves therapeutic CNS levels upon i.p. or oral dosing in mice. In vivo brain imaging experiments in mice (1) have shown that i.p. administration of the compound dramatically alters pathogenic Tat-induced leukocyte trafficking and microglial activation, and reverses Tat-induced damage to synaptic architecture (2). The NIH program grant will provide approximately $1.3 million dollars to Califia Bio to optimize and develop the series of compounds to provide effective and safe treatments for HAND. URMC and Califia Bio have requested NIH Rapid Access to Interventional Development (RAID) XO1 support to help to quickly obtain IND supporting safety studies for this lead series to advance these compounds for treatment of the underserved patient population of people living with AIDS. While recent advances in anti-viral treatments have greatly extended life expectancy of HIV infected individuals, HIV-associated neurological disease negatively affects approximately one half of AIDS patients, limiting the ability of patients to maintain employment and independence, and increasing the need for long-term home and institutionalized care. Effective treatments for HAND will improve quality of life and decrease patient dependence on long-term institutionalized health care.
(1) Marker DF, Tremblay ME, Lu SM, Majewska AK, Gelbard HA. A thin-skull window technique for chronic two-photon in vivo imaging of murine microglia in models of neuroinflammation, J Vis Exp. 2010 Sep 19;(43). pii: 2059.
(2) D. F. Marker, S.-M. Lu, M.-È. Tremblay, A. K. Majewska, H. A. Gelbard; “Pharmacologic inhibition of mixed lineage kinase 3 reduces neuroinflammation and neuronal pathology in mice exposed to human immunodeficiency virus type 1 trans-activator of transcription (TAT) protein. 2010 Neuroscience Meeting, San Diego Poster#: 346.7/H48.
