RARE Daily

Repurposed Drug May Help Stabilize Vision in Ultra-Rare Disease

June 19, 2024

Rare Daily Staff

A new study from researchers at Washington University School of Medicine in St. Louis found that the rare condition known as retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations may be stabilized by the use of an FDA-approved drug for a different condition.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is marked by progressive vision loss, cognitive decline, dementia and mini strokes, among other neurological manifestations. In the 1980s, two physicians from Washington University initially linked the symptoms to compromised small blood vessels that cause loss of blood flow to retinal, brain, kidney and liver tissues. The inherited mutations make themselves known when patients reach their 40s. Changes in vision start a cascade of symptoms leading to death in five to 20 years.

“Imagine a traffic jam,” said first author Wilson Wang. “Small blood vessels are the roads feeding into the circulatory highway system. When blood flow trickles, oxygen and nutrients cannot reach the tissue, and damage ensues.”

Other diseases cause similar circulatory system traffic jams. For instance, blockages in small blood vessels are responsible for episodes of excruciating pain in sickle cell disease. Their study was published June 17 in The Journal of Clinical Investigation.

Because there is an FDA-approved drug – crizanlizumab – used to help alleviate pain by unclogging congested small blood vessels and preventing blood cells from sticking to the vessel walls in sickle cell anemia patients, co-senior author Andria Ford, professor of neurology and of radiology, launched a clinical trial to test the drug in RVCL-S patients. A collaboration with Apte – an expert in retinal vascular diseases such as diabetic retinopathy and macular degeneration, conditions affecting blood vessels in the retina – focused on patients’ vision, retinal structure, and function.

The researchers set out to see if crizanlizumab helps to improve blood flow in the eyes and brain, explained Ford, who is co-director of Washington University’s RVCL Research Center and senior investigator on a parallel study looking at crizanlizumab’s effect on brain lesions in the clinical trial participants.

Eleven RVCL-S patients participated in the clinical trial for two years. They received two doses of crizanlizumab in the first month, followed by subsequent monthly infusions.

Images of retinal blood vessels highlighted with fluorescein dye were obtained at baseline and after the first and second years of the study. The images were analyzed and compared with images taken before the patients were treated with the drug and the amount of space lacking blood flow in a defined region of the retina, a measurement referred to as the nonperfusion index, was calculated.

After two years on the drug, trial participants saw their nonperfusion indexes plateau, a sign that loss of small blood vessel integrity was slowing, the researchers explained. Routine eye exams revealed that the participants’ vision had stabilized.

Preserving vision in a disease that often ends in blindness has the potential to give patients additional years to read, drive, and enjoy activities that bring them happiness. But future studies are needed to test the drug’s ability to slow vision loss in RVCL-S. In a parallel study, the researchers will examine the medication’s impact on brain lesions. If blood vessel blockages in the retina correlate with the brain lesions in these patients, the retina could be used as a biomarker for the systemic disease, Apte says.

“Until we have a genetic cure, our patients need treatments that halt or slow the progression of the illness,” Ford said. “Washington University is at the forefront of RVCL-S research. Decades of dedication have paved the way for this clinical trial. It represents our commitment to finding treatments that can alter the course of the fatal, rapidly progressing illness.”

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