Discovery of inflammation trigger may lead to new treatment for both lupus and macular degeneration

CHARLOTTESVILLE, Va. — Lupus, a potentially fatal autoimmune disease, and macular degeneration, a leading cause of blindness, have little in common on the surface. However, a new study has discovered a link that triggers both conditions — a genetic source of harmful inflammation.

Researchers from the University of Virginia say their findings may lead to the development of new treatments for both diseases as well as others which this inflammatory source drives.

“We were quite surprised at the common link between lupus and macular degeneration,” says Dr. Jayakrishna Ambati, the founding director of UVA’s Center for Advanced Vision Science, in a university release. “It appears that the new inflammatory pathway we identified could be therapeutically targeted for many chronic diseases.”

Ambati macular degeneration
Jayakrishna Ambati (Credit: UVA Health)

Ambati, a top macular degeneration researcher, and his team found a previously unknown role of the inflammasome NLRC4-NLRP3. Inflammasomes are “agents” of the human immune system which normally muster the body’s defenses together to fight off invaders like viruses and harmful bacteria.

However, NLRC4-NLRP3 appears to contribute to harmful inflammation in patients with either lupus or atrophic macular degeneration.

With lupus, the inflammasome drives the overactive immune response that contributes to patients experiencing symptoms including joint pain, rash, and fever. With macular degeneration, the study finds NRC4-NLRP3 drives inflammation which destroys the light-sensing cells in a person’s retina — leading to vision loss.

Ambati’s team discovered why this is happening

Researchers found that a special type of genetic material called short interspersed nuclear element RNAs (SINE RNAs) activates the inflammasomes. Study authors note that this kind of RNA makes up over 10 percent of the human genome.

Normally, it springs into action in response to cell-stressing events such as infections, genetic damage, and aging. The inflammation SINE RNAs cause is also beneficial to the body as it fights off chronic diseases.

In patients with macular degeneration or lupus, Ambati found elevated levels of SINE RNAs. Moreover, his team also spotted a previously undiscovered genetic receptor for SINE RNAs called DDX17. Scientists have been trying to find this receptor for decades, which Ambati’s team says will help researchers better understand what triggers harmful levels of inflammation within the human body.

“These findings indicate that blocking a single inflammasome might not be enough, and that targeting both the NLRC4 and NLRP3 inflammasomes would be a superior strategy,” Ambati explains.

“We’re excited to have developed drugs called Kamuvudines that block this dual inflammasome, which we anticipate will be in clinical trials next year.”

The study appears in the journal Science Immunology.

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