Using Computers To Repurpose Existing Drugs in Treating Rare Diseases

There is a great need for finding new treatments for patients with rare diseases. However, time and effort investments for discovery of new drugs from scratch are formidible. An alternative approach that is gaining momentum, not only for orphan disease research, is the repositioning of existing drugs. This consists of finding a new use for already approved drugs that were first developed to treat a different condition. Sildenafil, more commonly known as Viagra, is the most famous example of a repurposed drug. It was first developed to treat hypertension and angina, but side effects that were observed during clinical trials led to the drug being repurposed to treat erectile dysfunction.

Drug repositioning has several advantages over traditional drug discovery-- the most important being that it can become available sooner to patients. Before any drug is approved to enter the market, clinical studies must prove its safety and efficacy. Although clinical studies would have to be run to prove the efficacy of the repurposed drug for the new condition, safety has already been demonstrated. This implies that both the cost and time to market are greatly reduced. Indeed, drug repositioning is an strategy that will likely be of great importance for the development of new therapies for rare diseases. In fact, new legislation is in the works to promote repositioning in orphan disease research treatments: the Orphan Product Extensions Now Accelerating Cures and Treatments (OPEN) Act.

Recently, a group of researchers from Louisiana State University have published a computational method that could aid in this proccess. They have developed informatic tools that are able to identify proteins associated with rare diseases that could potentially bind to existing drugs. They have identified 381 existing drugs that could potentially have an effect on 761 proteins that are associated with 980 rare diseases on Orphanet. As an example, they have found that the drug exemestane might be used to target the protein NPC2 to treat Niemann-Pick disease type C. Niemann-Pick disease is a fatal hereditary disorder characterized by the accumulation of cholesterol in the lysosomes, an specialized compartment within the cell. It is caused by alterations on proteins that participate in cholesterol transport called NPC1 or NPC2. Exemestane is currently used in the clinic to treat breast cancer.

The results of this study, which are publicly available, can hopefully encourage similar research that would help to find new treatments for other rare diseases.