Approximately 50 families scattered across the world share ultra-rare variants in a particular gene. Silent for years, the inherited mutations cause changes in vision when patients reach the fourth decade of life.
The visual changes start a cascade of symptoms. Five to 20 years later, the rare condition known as retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is fatal.
Researchers at Washington University have reported that a drug, approved by the United States Food and Drug Administration for sickle cell anaemia, may stabilise vision for patients with RVCL-S.
“Fifty per cent of family members with these genetic mutations will inherit the disease,” said the study’s co-senior author, Professor Rajendra S. Apte.1 “These families are devastated by this illness, and we have not been able to offer them much hope.
“However, our new findings suggest that an already approved medication for a different disease may have the potential to help these patients, although additional studies are needed.”
TRAFFIC JAM
RVCL-S is marked by progressive vision loss, cognitive decline, dementia, and mini strokes, among other neurological manifestations. In the 1980s, 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.
“Imagine a traffic jam,” explained first author Dr 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.”
Because there is an FDA-approved drug – crizanlizumab – that acts to unclog congested small blood vessels and prevent blood cells from sticking to the vessel walls in sickle cell anaemia patients, the team launched a clinical trial to test the drug in RVCL-S patients.
Eleven RVCL-S patients participated in the clinical trial for two years. After two years, researchers saw signs that loss of small blood vessel integrity in trial participants was slowing, and eye exams revealed that their vision had stabilised.
Preserving vision has the potential to give patients additional years to read, drive and enjoy everyday activities but is not a cure for the disease.
The study was published in The Journal of Clinical Investigation.2
References
- Washington University School of Medicine, Repurposed drug may help stabilize vision in rare disease (media release) 17 June 2024. Available at: Eeurekalert.org/news-releases/1048219 [accessed June 2024].
- Wang, W.X., Spiegelman, D., Apte, R.S., et al., Crizanlizumab for retinal vasculopathy with cerebral leukoencephalopathy in a phase II clinical study. The Journal of Clinical Investigation. 2024;134(12). DOI: 10.1172/JCI180916.
