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Subspecialties Diabetes, Retina

A New Purpose

Montelukast – a leukotriene inhibitor – is well known to asthma sufferers, who benefit from its proven ability to prevent wheezing and shortness of breath. But researchers believe it may have a new indication: diabetic retinopathy. A team at the University Hospitals Rainbow Babies and Children’s Hospital and Case Western Reserve University School of Medicine studied the effect of montelukast on diabetic retinopathy – a condition characterized by neuronal and vascular degeneration – using a mouse model of type 1 diabetes. The results were impressive: after nine months, the retinal microvasculature from untreated diabetic mice demonstrated a nearly threefold increase in capillary degeneration compared to mice treated with montelukast. We spoke to senior author Rose Gubitosi-Klug, Chief of Pediatric Endocrinology at UH Rainbow and the William T. Dahms Professor of Pediatrics at CWRU School of Medicine, to find out more.

Is there any prior research on montelukast being applied to diabetic retinopathy?

No. But the retina is nervous system tissue and montelukast has been shown to help protect neurons in models of other diseases, such as neurodegenerative diseases by multiple sclerosis.

How significantly did the drug affect degeneration in the study?

Montelukast dramatically helped reduce damage to retinal blood vessels. In diabetes, the small blood vessels or capillaries first degenerate – this sets up areas of poor blood flow in the retina and, in time, this leads to advanced diabetic eye disease where vessels try to grow back. As a result, they end up growing aberrantly – it is called proliferative diabetic retinopathy – so much so that vessels can be easily damaged, which might result in retinal hemorrhages that cause vision impairment. Montelukast worked to almost completely prevent the diabetes-related degeneration of capillaries and reduce the generation of VEGF, which causes the vessels to try and grow back erratically. Where nerves are concerned, Montelukast did help with survival of neurons long term, but short-term studies did not show significant improvement in function. More research is needed to understand this finding.

What is the mechanism of action?

We believe it works in a couple of ways. First, by preventing leakage of blood vessels, which makes them more susceptible to degeneration through cysteinyl leukotriene receptor 1. Second, by blocking the generation of leukotriene B4.

How soon do you think you’ll be able to translate the study to human subjects?

We have a manuscript in preparation that looks at the leukotriene cascade in white blood cells from human subjects, which is the first step to translate the findings. We have more clinical studies planned in the coming year.

What are the benefits of repurposing medication?

Repurposing significantly speeds up the timeline to treatment of a new disease. All of the safety studies required of medications have been completed, so we can go straight to advanced clinical trials. A benefit of the drug is that you can orally administer it as a tablet once a day – no injections or procedures are necessary. We envision using this someday as preventative medication, starting in adolescence. With a safe profile and daily dosing, there are few drawbacks to trying montelukast!

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  1. R Bapputty et al., “Montelukast Prevents Early Diabetic Retinopathy in Mice”, Diabetes, 98, 8 (2019). PMID: 31350303.
About the Author
Phoebe Harkin

Associate Editor of The Ophthalmologist

I’ve always loved telling stories. So much so, I decided to make a job of it. I finished a Masters in Magazine Journalism and spent three years working as a creative copywriter before itchy feet sent me (back)packing. It took seven months and 13 countries, but I’m now happily settled on The Ophthalmologist, where I’m busy getting stuck into all things eyeballs.

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