Drug repurposing shows promise in treating retinal degeneration, according to a new study from an international team of researchers, published in Nature communicationCombination treatment with three existing drugs – tamsulosin, metoprolol and bromocriptine – slowed disease progression in preclinical retinopathy models.

Drug repurposing refers to the use of existing medications to treat diseases or conditions for which they were not originally developed or approved. The new study focused on drug repurposing in the context of inherited retinal degenerations, IRDs.

IRDs are a group of genetic diseases that cause the deterioration of retinal anatomy and function, leading to progressive vision loss and often blindness. Most IRDs are currently therapeutically inaccessible, representing an unmet medical need for a significant population worldwide.

A combination treatment with three drugs slowed the progression of the disease

The researchers found that a three-drug combination treatment significantly slowed disease progression and reduced disease manifestations in four different animal models of IRD. The combination included the blood pressure and heart failure drug metoprolol and tamsulosin, which is used to treat benign prostatic hyperplasia, as well as the now less commonly used Parkinson’s drug bromocriptine.

“When repurposing drugs, it doesn’t matter what diseases or conditions the drugs were originally developed for, it’s the effects of drugs at the molecular level, or pharmacology, that counts,” said Dr. Henri Leinonen, the paper’s first author, currently associate professor of neuropharmacology at the University of Eastern Finland and previously a postdoctoral researcher at the University of California, Irvine.

In retinal degeneration, intracellular second messengers such as cyclic adenosine monophosphate and calcium are thought to be overactive, thereby worsening the disease. Metoprolol, tamsulosin, and bromocriptine suppress the activity of these second messengers through their own separate cell membrane receptor actions.

“We hypothesized that the combined effect of these drugs would alleviate the disease, which was indeed the case in several separate animal models of IRD. However, the efficacy and safety of this combination in humans with retinal degeneration is not guaranteed and controlled clinical trials to test this are needed,” Dr. Leinonen notes.

It is noteworthy that none of the drugs used in the study were effective against retinal degeneration on their own; instead, their combination was necessary for efficacy. According to Dr. Leinonen, the same phenomenon may apply to many diseases that are currently untreatable, and especially in multifactorial diseases, effective treatment may require multiple drugs to be used simultaneously.

Repurposing medicines can provide solutions, especially for the treatment of rare diseases

Rare diseases, including IRDs, are rarely of great interest to the pharmaceutical industry due to a lack of economic incentives. However, drug repurposing, an active research topic in academia, is a promising method to find solutions for rare diseases that remain therapeutically inaccessible.

The main advantages of repurposing drugs are found in faster drug development times and lower costs. Because repurposed drugs have already undergone several mandatory safety tests and early stages of clinical trials, their market introduction is significantly faster and cheaper than that of completely new drugs.

Drug safety is also an important aspect, as the relative safety of repurposed drugs compared to a completely new chemical reduces risk and uncertainty. This is often seen as the most critical point in the drug development process.