Treatment of HIV-Associated Neurocognitive Disorders (HAND)

Categories: “Viruses, Chronic & Infectious Diseases” “Neurological Disorders“

Reference #: 2019-036

OTC Contact: Zeinab Abousisa. (Directory Information | Send a Message)

Description

Despite successful antiretroviral drug therapy, a subset of HIV positive individuals still display synapto-dendritic simplifications and functional cognitive impairments referred to as HIV-associated neurocognitive disorders (HAND). HIV envelope protein gp120 is a potential contributing factor for loss of synapses seen in a subset of HIV positive individuals who develop HAND. Among mechanisms proposed to explain gp120’s neurotoxicity is the alteration of axonal transport, which relies on acetylation of neuronal tubulin. Gp120-mediated tubulin deacetylation, which is mediated by histone deacetylase 6
(HDAC6), impairs the association of key motor proteins, with the microtubule, and thus damages axonal transport.

Using primary rat neuronal cultures, researchers at Georgetown University’s Department of Neuroscience demonstrated that ACY-1215, a potent and selective HDAC6 inhibitor currently in clinical trials as an anti-cancer therapy (Ricolinostat), prevents gp120-mediated deacetylation of tubulin, as well as gp120-mediated neurite shortening and cell death.

Applications

• HDAC6 inhibition as a viable therapeutic strategy to reduce synaptopathy and neuronal damage seen in HAND patients

Advantages

• At present there is no cure for HIV-associated neuronal degeneration (HAND). HDA6 inhibitors are clinically used for cancer and thus this invention proposes a novel therapeutic intervention for HAND

Inventors

Italo Mocchetti, Ph.D.

Patent Status

Provisional patent application filed