Inflammasome Therapeutics reported that data analyses published in the current issue of Proceedings of the National Academy of Sciences (PNAS) confirms that the company’s proprietary compounds hold significant promise in the prevention and treatment of dry age-related macular degeneration (dry AMD). Dry AMD affects 85% of people with AMD and no current treatments are available; wet AMD affects 15% of patients with numerous treatments available and represents a multi-billion dollar market.
The PNAS paper, authored by Jayakrishna Ambati, MD, at the University of Virginia School of Medicine, along with Salk Institute for Biological Studies’ Fred H. Gage, PhD, and collaborators from around the world, reveals that patients taking certain drugs to prevent HIV infection have a 40% lower risk of developing dry AMD compared to matched controls.
The drugs, nucleoside reverse transcriptase inhibitors (NRTIs), have been used for decades to fight HIV. In a 2014 publication in Science, Dr. Ambati found that NRTIs not only inhibit HIV replication but also inhibit part of the immune system—inflammasome activation—and that inflammasome inhibition by NRTIs prevented dry AMD in animal models. NRTIs have systemic toxicity that would limit their use in AMD but Dr. Ambati also found that low toxicity derivatives of NRTIs (Kamuvudines) also block inflammasome activation and are at least as effective as NRTIs in dry AMD.
Dr. Ambati and the team at Inflammasome Therapeutics are developing Kamuvudines as treatments for dry AMD and several other chronic diseases.
“The present study provides the missing link between animals and humans,” said Dr. Paul Ashton, president and CEO of Inflammasome Therapeutics. “The authors analyzed insurance claims data bases covering more than 100 million Americans, so the data are extraordinarily robust. Importantly, the study indicates the type of response that we can expect from Kamuvudines and de-risks our planned clinical program. We know Kamuvudines and NRTIs have the same effect on inflammasome activation; we know they are both highly effective in animal models of AMD; and now we know NRTIs can prevent AMD in humans. We hope to demonstrate as we move into the clinic this year that Kamuvudines work in people.”
“We believe Kamuvudines may be effective against a large number of prevalent degenerative diseases involving inflammasome activation such as multiple sclerosis, Alzheimer’s and type II diabetes,” said Dr Ambati. “The present paper is very encouraging following our September 2020 publication in Nature Communications that showed use of NRTIs is associated with a 30% reduced risk of developing type 2 diabetes.”
Inflammasome Therapeutics was founded by Jayakrishna Ambati, MD, and Paul Ashton, PhD, in 2016 to develop therapies for prevalent, degenerative diseases. The company combines scientific excellence with proven development expertise and works to develop products via a mixture of licensing agreements and internal development. Inflammasome currently has collaboration agreements with Boehringer Ingelheim and the Bill & Melinda Gates Foundation.