In the largest clinical observational study to date, researchers from Washington University School of Medicine in St. Louis reported that crizanlizumab, an FDA-approved drug for sickle cell disease, may help stabilize vision in patients with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S). The findings, published in The Journal of Clinical Investigation, suggested a potential disease-modifying treatment.

RVCL-S is caused by mutations in the TREX1 gene. Symptoms typically appear in the fourth decade of life and include progressive vision loss, cognitive decline, dementia, and mini strokes. 

The Phase 2 study included 11 patients with RVCL-S who received monthly infusions of crizanlizumab. The treatment prevents blood cells from adhering to vessel walls, thus improving blood flow in small blood vessels.

After 2 years of treatment, retinal imaging showed that patients' nonperfusion indexes – a measure of the area lacking blood flow in the retina – had plateaued, suggesting a slowing of small blood vessel damage. The total change was 7.22% in year 1 and -0.69% in year 2. Eight of 11 patients reported mild side effects. 

A post-hoc analysis showed that patients who withdrew from the study had a 24.3% higher overall nonperfusion and 26.7% higher nonperfusion in the far periphery compared to those who completed the study. Although limited by the small sample size, the study suggested disease severity likely played a role in patients' ability to adhere to treatment. The average time from TREX1 mutation diagnosis was 5 years in those who withdrew versus 1.6 years for completers, further indicating more severe disease in the dropout group.

While the findings are promising, the researchers noted further studies are needed to confirm the treatment's ability to slow vision loss in RVCL-S. A parallel study will investigate the medication's effect on brain lesions.

Leukocyte adhesion and recruitment may play a role in the pathology of RVCL-S and potentially similar small-vessel diseases, concluded investigators. The results raise the possibility that targeting cell adhesion pathways could have implications for treating other retinal vasculopathies, but further research is needed.