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Scientists have identified a group of drugs that could help stop one of the leading causes of vision loss after making an unexpected discovery that overturns a fundamental belief in DNA.
Medicines called nucleoside reverse transcriptase inhibitors, or NRTIs, are commonly used to treat HIV. The new finding suggests that they may also be useful against dry macular degeneration, even if a virus does not cause this condition of sight theft.
A review of four different health insurance databases suggests that people taking these drugs significantly reduced the risk of developing dry macular degeneration, a condition that affects millions of Americans.
“We are extremely pleased that the reduced risk has been replicated in all databases, each with millions of patients,” said Jayakrishna Ambati, MD, one of the top macular degeneration researchers in the United States. Medicine School. “This discovery gives real hope in the development of the first treatment for this blinding disease.”
TARGETING MACULAR DEGENERATION
The new discovery comes from Ambati; Fred H. Gage, PhD, of the Salk Institute for Biological Studies; and collaborators around the world. The book rewrites our understanding of DNA, revealing for the first time that it can be made in the cytoplasm of our cells, outside of the cell nucleus that houses our genetic material.
The accumulation of a certain type of DNA in the cytoplasm, Alu, contributes to macular degeneration, the researchers found. This buildup appears to kill a large layer of cells that nourish the visual cells in the retina.
Based on this finding, the researchers decided to examine drugs that block the production of this DNA, to see if they could help prevent vision loss. They analyzed several U.S. health insurance databases – covering more than 100 million patients over two decades – and found that people taking NRTIs were almost 40% less likely to develop dry macular degeneration.
Researchers are calling for further study to determine whether these safer drugs or derivatives known as Kamuvudins, both of which block a key inflammatory pathway, could help prevent vision loss from dry macular degeneration.
“A clinical trial of these inflammasome inhibitor drugs is now warranted,” said Ambati, founding director of UVA’s Center for Advanced Vision Science. “It is also fascinating how the discovery of the complex biology of genetics and its combination with the archeology of big data can propel information on new drugs. “
Ambati, from the UVA Department of Ophthalmology, previously determined that NRTIs can help prevent diabetes also.
Reference: 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. 2021; 118 (6). do I:10.1073 / pnas.2022751118
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