Kamuvudines for the Treatment of Advanced AMD

Article: HIV Drugs May Help Prevent Blinding Macular Degeneration
Source: University of Virginia Health, via NEI
Published: February 1, 2021
Article: HIV Drugs May Be Repurposed for Blindness
Source: Genetic Engineering & Biotechnology News
Published: February 2, 2021

Jayakrishna Ambati, MD, professor of ophthalmology and founding director at the Center for Advanced Vision Science at the University of Virginia, recently published a study in Proceedings of the National Academy of Sciences showing the strong correlation between patients taking nucleoside reverse transcriptase inhibitors (NRTIs), FDA-approved anti-HIV drugs, and reduced risk of developing advanced dry macular degeneration. This observational study is extraordinarily robust, applying "big data archeology" to four different health insurance databases comprising more than 100 million American, of which 35 million records were analyzed. The data of reduced risk was found in all of the databases, approximately 40% reduced risk overall, which is a significant finding. An earlier study by Ambati's team published in Nature Communications showed that the use of NRTIs is associated with a 30% reduced risk of developing type 2 diabetes, providing an estimate for the team's further studies into the effect of NRTIs and kamuvudines (less toxic derivatives) on degenerative diseases that involve inflammasome activation, including macular degeneration such as in the present study, but also multiple sclerosis and Alzheimer's disease. Given the robust data on the effect of these drugs that are already FDA-approved to treat HIV in humans, the drugs have great potential to be repurposed for off-label use in the treatment of advanced macular degeneration. While there are eye vitamins following the AREDS2 formulas to promote eye health in some forms and stages of dry macular degeneration, there is as yet no therapeutic treatment for the disease at this point. As Ambati states, “A clinical trial of these inflammasome-inhibiting drugs is now warranted."

Personal commentary: It is rare that I think a study that appears in general science news outlets is a five-star study. This is not because I am picky but because most such studies involve clinical trials at the final leg of the research marathon. The magnitude and subject matter of those studies are necessarily excellent and are reported upon by much more experienced commentators than I. Once in a while, however, there is a study that is technically basic science or observational science, but contains the magnitude of clinical trials. In the study above, for example, these drugs are already FDA-approved for HIV treatment. The population size is enormous. The discovery was made through meticulous data mining. And finally, though the nuances of Alu elements and various transcription enzymes are best appreciated in the coverage by Genetic Engineering & Biotechnology News, the study provides new information to areas of foundational science, in this case genetics. For example, in addition to DNA in the nucleus and in mitochondria, DNA is also found in the cell's cytoplasm; it is this cytoplasmic DNA that the researchers investigated in the degeneration of retinal pigment epithelium (RPE) cells, the malfunctioning of which leads to macular degeneration.

My rating of this study: ⭐⭐⭐⭐⭐

Further reading: Human Cells Can Synthesize DNA in Their Cytoplasm

Edit note: The above as been edited to include the detail that Ambati's study analyzed nearly 35 million patient records in four insurance databases comprising over 100 million Americans.

Fukuda S, Varshney A, Fowler BJ, et al. "Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration." PNAS.  118(6):e2022751118. 9 February 2021. https://doi.org/10.1073/pnas.2022751118