Grant: Operating Grant - PA: HIV/AIDS Bridge Funding - Biomedical/Clinical Stream

Worldwide, millions of patients infected with Human Immunodeficiency Virus (HIV) suffer from sensory nerve pain (HIV-SN) and numbness in their hands and their feet. The success of anti-retroviral medication means HIV patients are no longer dying from the disease. Instead they are living with chronic exposure to this 'nonreplicating' HIV virus which can lead to secondary effects such as HIV-SN. There is no treatment for HIV-SN as pain medications are ineffective; therefore a novel treatment is desperately needed. We will test the ability of the novel p75 neurotrophin receptor (p75ntr) antagonist LM11A-31 (LM) for treating HIV-SN and loss of skin innervation at the site of HIV-SN. We will test the overarching HYPOTHESIS that: LM successfully treats HIV-SN. The overarching hypothesis is based on our published observations showing that: 1. Chronic expression of HIV viral protein R (Vpr) in our HIV-mouse model leads to chronic pain and loss of nerve innervation at the footpad, as seen in HIV patients. 2. Vpr exposure in cultured rodent and human sensory neurons inhibits axonal growth and this is prevented by blocking p75ntr. 3. The drug LM blocks the p75ntr in multiple animal models and has been shown to be safe and effective. LM is currently undergoing Phase 1 clinical trials which means it will likely be approved for human use by the time our proposal is complete (personal communication from our collaborator, and engineer of this drug, Dr. Frank Longo). In summary, our proposal will test the ability of LM to treat HIV-SN and prevent the loss of epidermal nerves in the footpad of our HIV mouse model. This would provide the basis for a Phase 2 Clinical trial to treat HIV-SN patients with LM in hopes to cure to this debilitating condition.