New research out of the National Institutes of Health (NIH) supports the use of an FDA-approved compound to preserve light-sensitive photoreceptors in pediatric cases of Leber Congenital Amaurosis (LCA).
Talk about this type of LCA first.
LCA type 10 (LCA10) is an inherited retinal ciliopathy disease that typically leads to either severe visual impairment or blindness in pediatric patients.
LCA10—caused by mutations from a cilia-controsomal gene called CEP290—is the most common gene associated with LCA, accounting for 20 to 25% of all cases. Due to mutations in CEP290, retinal cells in LCA10 experience primary cilium dysfunction.
Now tell me about the study.
Researchers designed a mouse model study on LCA10 using two types of retinal organoids (miniaturized and simplified version of an organ) that were differentiated from induced pluripotent stem cells (iPSC) of the rd16 mutation.
They then performed an unbiased, high-throughput screening of 6,000+ FDA-approved compounds in order to identify which could support photoreceptor survival (and potentially visual preservation).
Findings?
They identified five potential FDA-approved drug candidates for treating LCA, including Reserpine, previously indicated for high blood pressure.
Reserpine was found to maintain photoreceptor development and survival in the rd16 organoids as well as improve the organoids derived from iPSC of LCA10 patients and in the rd16 retina mice in vivo.
These models also uncovered dysregulation of autophagy (where cells break down old or abnormal proteins) of the primary cilium biogenesis within patients’ organoids and the rd16 mouse retina.
What else did Reserpine do?
Reserpine appeared to partially restore autophagy—leading to improved assembly of the primary cilia—by targeting intracellular signaling pathways that were poorly regulated downstream of the primary cilium.
Significance?
The effectiveness of Reserpine shows potential for treating retinal ciliopathies caused by 160+ disease-induced genes (including LCA).
Take home.
According to investigators, the findings suggest that ongoing monitoring for potential glaucoma development in patients post-lensectomy is needed at any age.