A new study from researchers at Johns Hopkins Medicine’s Wilmer Eye Institute has produced suggestive evidence that a new experimental drug may slow or even prevent vision loss in patients with diabetes.
Give me some background.
Proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) are both well-known ocular diseases that can occur in patients with diabetes.
Both diseases are frequently treated with anti-vascular endothelial growth factor (VEGF) therapies, but less than half of patients with either disease might not respond adequately to these treatments.
The angiogenic proteins regulated by hypoxia-inducible factor (HIF)-1 and -2 have been observed in diabetic eyes even following anti-VEGF therapy, suggesting an alternative route for diabetic retinopathy (DR) treatment.
Talk about the research.
Using streptozotocin (STZ)-induced diabetic mouse models, the researchers assessed the efficacy of two HIF inhibitors: acriflavine and a novel HIF inhibitor 32-134D, for treating both PDR and DME.
Give me some details.
The study explored acriflavine along with digoxin and doxorubicin, which are known to be pharmacologic HIF inhibitors. However, investigators noted that digoxin and doxorubicin were unlikely to be well-tolerated by patients coupled with increased risk of retinal toxicity. Further, acriflavine accumulated in the neurosensory retina, inhibiting retinal function over time.
Therefore, they looked for a different HIF inhibitor that was structurally unrelated to acriflavine leading to the identification of HIF inhibitor 32-134D, which became the focus of the study.
Findings?
They found that HIF inhibitor 32-134D inhibits HIF accumulation and the expression of HIF-regulated genes in retinal Müller cells, vascular endothelial cells, and human-inducible pluripotent stem cell-derived 3-dimensional retinal organoids.
Intraocular administration of 32-134D did not affect retinal histology or function but instead resulted in a sustained effective drug concentration in the retinal tissue following a single intravitreal injection.
So what does that mean?
While the researchers noted that further studies in animal models are needed before 32-134D can move to clinical trials, the results thus far are promising.
Anti-VEGF therapies are a popular approach for PDR and DME, but alternative routes could offer crucial treatment options for the many patients who do not respond to these medications.