The answer to the question in the title of this post is “Yes, drug repurposing does work” and in this short blog we shall discuss examples of its utility in Parkinson’s. But first it would be wise to explain the drug development process and why drug repurposing is an exciting area of research that is receiving a lot of attention.

Drug development is a very long and extremely expensive process. It starts with the identification of a molecule that can target and manipulate a particular biological pathway. The chemistry of that agent is then thoroughly investigated and characterized before it is then tested in models of medical conditions. If the molecule proves to be effective in those models, it is next tested for toxicities and potential side effects. All this effort takes large budgets, and it occurs years before the drug ever even gets close to being exposed to any human beings. The failure rate at each of these steps is very high, but this ultimately helps to filter down to a few agents that are safe and worthy of testing in humans.

Once clinical testing starts, there are multiple phases of evaluation – starting with short assessments of safety and tolerability (this is referred to as Phase 1 testing). This step typically occurs in healthy volunteers and also helps to determine potential dosing. If all goes well, larger and longer clinical trials are next conducted in the patient group of interest to determine long-term safety and tolerability and to see if there is any evidence that the drug actually does what it is supposed to do. These studies are termed Phase 2 and Phase 3 trials – Phase 3 being the largest and longest, and they are considered the penultimate test before any regulatory approval can be given. Collectively, this entire process can take several decades to finally get a drug to the stage where health regulators are deciding on whether to approve this new medication for clinical use.

While cautious and prudent, the drug development process is obviously a very slow and inefficient path. But efforts have been made to speed it up.

One example of this is drug repurposing (also known as drug repositioning).

Drug repurposing involves testing treatments that are already clinically available. There are currently over 20,000 prescription drugs approved by regulators for clinical use. Given that all of these agents have previously been well characterized in terms of their chemistry, toxicity, safety and tolerability, and approved for another medical condition, they represent a useful reservoir that can be screened and rapidly shifted into Phase 2 clinical testing for alternative medical ailments. As a result, several steps in the drug development process can be skipped, greatly speeding up the drug development process and representing a means of rapidly bringing novel therapies to a patient community.

And drug repurposing has already been shown to be effective in Parkinson’s.

Amantadine was originally developed as an antiviral treatment for influenza in the 1960s, but resistant strains of the virus began appearing in the 1980s, which rendered the drug ineffective. Amantadine gained new life, however, following an incidental observation in 1969, which led to it being repurposed for Parkinson’s: A woman with Parkinson’s was administered amantadine to help treat an influenza infection. She reported to her doctor that her Parkinson’s symptoms improved significantly while on amantadine, and then they worsened after she finished the treatment. Clinical trials were quickly conducted and amantadine was found to be a very effective symptomatic therapy for Parkinson’s. In 1973, the US FDA approved amantadine for the treatment of motor symptoms in Parkinson's. 

Drug repurposing efforts continue even now with a focus on agents that could do more than simply alleviate Parkinson’s symptoms, but hopefully slow down the progression of the condition. A good example of this is the drug exenatide, which is widely used as a diabetes treatment. Exenatide has previously been reported to exhibit neuroprotective properties in models of Parkinson’s and encouraging results have been achieved in two clinical trials which has provided justification for the initiation of a large Phase 3 study currently being conducted in the UK.

One positive outcome of drug repurposing is that similar therapies might also be tested, bringing further interest from different parties. And we see this in the case of exenatide, where there are multiple ongoing Phase 2 trials in Parkinson’s for drugs that are very similar to exenatide (such as liraglutide and lixisenatide – both of which will be reporting results in 2022). Another positive feature of drug repurposing is the development of new and better versions of the repurposed molecule. For example, a new extended-release formulation of amantadine (called Gocovri) was developed and approved in 2015 for clinical use in Parkinson’s. In addition, multiple biotech companies are now developing exenatide-like drugs for Parkinson’s (such as Neuraly and Peptron), based on the initial clinical trial results of the repurposed drug. In this manner, drug repurposing can provide the ‘proof-of-concept’ evidence that is required before further refinement and improvement of a treatment is undertaken to provide additional benefits to patients.

Drug repurposing is currently being applied to Parkinson’s across multiple ongoing clinical trials. For example, a gall stone treatment called UDCA and a prostate treatment named terazosin have both been tested in people with Parkinson’s based on interesting preclinical results indicating that they can enhance the metabolism of cells in the brain. Similarly, a drug that removes iron from the body - called deferiprone - has been tested in Parkinson’s to test if accumulation of iron in vulnerable areas of the brain is involved with the progression of the condition. And a new Phase 3 clinical trial is being set up for the respiratory drug known as ambroxol, which has been shown to elevate levels of a Parkinson’s associated enzyme in patients. 

So, as stated in the first paragraph of this blog, yes – drug repurposing does work, and it represents a rapid method of delivering novel treatment options to the patient community. The research community are actively exploring new opportunities to reposition old therapies Parkinson’s, and the learning from the trials being conducted will also hopefully provide novel insights into the biology underlying the condition.

Full disclosure: The author is an employee of Cure Parkinson’s which is supporting many of the clinical trials mentioned in this blog.

Dr. Stott is the Deputy Director of Research at Cure Parkinson's. Simon has over 15 years of experience in the field of Parkinson's research - in both the academic and biotech industry sector. He has been involved in lab-based research as well as clinical studies, with a number of scientific publications. He also maintains the 'Science of Parkinson's' website, which attempts to explain in plain English the research currently being conducted on Parkinson's. Dr. Stott spoke about “What’s new on drug repurposing?” at the WPC Virtual Congress in 2021. See his talk here.

Ideas and opinions expressed in this post reflect that of the author solely. They do not reflect the opinions or positions of the World Parkinson Coalition®