NU 2022-207

INVENTORS 

• Elena Martinelli*

SHORT DESCRIPTION

A method for activating latent immunodeficiency virus infections using a TGF-beta inhibitor in order to treat HIV.

BACKGROUND

Current HIV treatments focus on inhibiting viral replication but fail to address latent HIV reservoirs, which pose a risk of reactivation and disease progression. These reservoirs consist of dormant HIV-infected cells that can become active at any time. The "kick and kill" strategy has been proposed to activate and eliminate these reservoirs, but existing therapies are insufficient to target latent infections. TGF-beta signaling plays a critical role in maintaining latency, and its inhibition offers a promising avenue for reducing these reservoirs and potentially achieving a functional cure for HIV.

ABSTRACT

Inhibiting TGF-beta signaling through a TGF-beta type 1 receptor inhibitor (galunisertib) reversed HIV latency across various models, including in vitro, ex vivo, and in vivo studies. This approach decreases latent HIV reservoirs in PBMCs from individuals on suppressive antiretroviral therapy and also decreases viral loads in gut tissue, lymph nodes, and blood in non-human primate models. In addition, the treatment also enhances anti-virus T cell responses and antibody titers, suggesting a dual benefit of latency reversal and immune activation. This innovative strategy could significantly impact the management of HIV by targeting persistent viral reservoirs that current therapies cannot eliminate.

APPLICATIONS

• HIV and SIV Treatment:
  • In combination with antiretroviral therapy, targets and reduces latent viral reservoirs in SIV and HIV-positive patients.

ADVANTAGES

• Latency Reversal:
  • Effectively reverses HIV latency while stimulating immune responses.
• Reservoir Reduction:
  • Decreases cell-associated viral DNA load in multiple tissues.

PUBLICATIONS

Martinelli et al, "Blockade of TGF-β signaling reactivates HIV-1/SIV reservoirs and immune responses in vivo," JCI Insight, September 20, 2022.

IP STATUS

US Patent Pending