A team of researchers has unveiled promising results in the treatment of retinal degeneration through drug repurposing, as detailed in a recent study published in the journal Nature Communications. The study demonstrated that a combination of three existing drugs—tamsulosin, metoprolol, and bromocriptine—slowed disease progression in pre-clinical retinopathy models.
Drug repurposing involves utilizing existing drugs to treat diseases or conditions for which they were not originally developed or approved. This new research focused on inherited retinal degeneration (IRDs), a group of genetic diseases that cause the deterioration of retinal anatomy and function, leading to gradual vision loss and often blindness. Currently, most IRDs lack therapeutic options, representing an unmet medical need for a substantial global population
Dr. Leinonen and co-workers found that a combination treatment using tamsulosin, metoprolol, and bromocriptine significantly slowed the progression of retinal diseases and reduced their impact in four different animal models of IRD. This treatment improved cone photoreceptor function and slowed degeneration in mice with retinitis pigmentosa. Metoprolol is commonly used for blood pressure and heart failure, tamsulosin for benign prostatic hyperplasia, and bromocriptine, previously used for Parkinson’s disease.
Research suggests that tamsulosin’s ability to improve blood flow and its neuroprotective properties might be beneficial in treating retinal diseases. Its vasodilatory effects could enhance retinal blood supply, potentially slowing disease progression. Metoprolol’s neuroprotective and anti-inflammatory properties could play a role in protecting retinal cells from degeneration. It might also help in managing intraocular pressure, which is beneficial in conditions like glaucoma that can co-occur with retinal degeneration. Bromocriptine’s neuroprotective and anti-apoptotic effects might help in preserving retinal cells. Additionally, its ability to modulate insulin resistance and oxidative stress could be advantageous in retinal health, particularly in diabetic retinopathy. According to Leinonen et al., the crucial factor in repurposing drugs is their molecular-level effects, rather than the diseases they were originally developed to treat.
In the context of retinal degenerations, intracellular secondary messengers such as cyclic adenosine monophosphate and calcium are believed to be overactive, exacerbating the disease. Metoprolol, tamsulosin, and bromocriptine suppress the activity of these secondary messengers through their distinct cell membrane-receptor actions. The combined effect of these drugs was hypothesized to alleviate the disease, which was confirmed in several distinct animal models of IRDs.
However, the efficacy and safety of this combination in humans with retinal degeneration are not yet guaranteed, necessitating controlled clinical trials. Notably, none of the drugs were effective against retinal degeneration on their own; their combination was essential for efficacy. This phenomenon, according to Leinonen et al., may apply to many currently untreatable diseases, particularly multifactorial diseases that may require multiple drugs used simultaneously for effective treatment.
Drug repurposing holds particular promise for the treatment of rare diseases, including IRDs, which often receive little attention from the pharmaceutical industry due to a lack of economic incentives. Nonetheless, it is an active research area in academia, offering potential solutions for therapeutically inaccessible rare diseases.
The significant advantages of drug repurposing include faster drug development times and lower costs. Since repurposed drugs have already undergone several mandatory safety tests and early-stage clinical trials, their market entry is considerably faster and cheaper than entirely new drugs. The relative safety of repurposed drugs also reduces risks and uncertainty, often considered the most critical points in the drug development process. This study highlights the potential of drug repurposing to address unmet medical needs in retinal degenerations and other rare diseases, offering a faster and cost-effective route to new treatments.
Reference
Leinonen H, Zhang J, Occelli LM, Seemab U, Choi EH, L. P. Marinho LF, et al. A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models. Nat Commun. 2024 Jul 15;15(1):5943.