By James Beck, Ph.D.
Cholesterol-lowering pills, chemotherapy and an injectable medication for diabetes: what do these three things have in common? Answer: they are all being tested for the treatment of Parkinson's disease (PD).
Increasingly, scientists are examining drugs that are already on the market for non-PD health conditions for their potential to treat Parkinson's. This idea is called "repurposing," or repositioning. And it's not unique to Parkinson's. Among the many examples of repurposing is a well-known blockbuster drug, sildenafil (Viagra®). In fact, the drug was originally intended to treat hypertension. In our own community of Parkinson's disease, deep brain stimulation, a surgery that was first approved for PD in the 1990s, is now being used to treat the neurological disorders known as essential tremor and dystonia.
In the past, repurposing drugs was simply a matter of serendipity. A doctor or scientist would notice that a drug intended to treat one health condition seemed to work for another one - typically, unrelated. But now, it is pursued as a deliberate tactic. In fact, in 2012, the National Institutes of Health announced $20 million in grants designed — in the words of Kathleen Sebelius, US Secretary of Health and Human Services — to "see whether we can teach old drugs new tricks."
The repurposing of existing drugs offers major advantages over the creation of new ones, mainly as it relates to efficiency. The reason: a drug already approved for the market by the US Food and Drug Administration (FDA) has already been proven safe for human use, which means that a drug company looking to explore alternative uses can quickly leapfrog one crucial and expensive stage of drug testing. For the company, this means welcome savings in dollars. And for people who so urgently need better treatments, it may mean savings in time. Could repurposing translate into better treatments at a faster pace for people with Parkinson's disease? At PDF, we thought it was time to take a critical look at why researchers are trying to repurpose drugs, what could be the possible benefits for the PD community, and what, if any, are the pitfalls to be encountered with this approach.
How It's Done: An Overview
Worldwide, there are nearly 6,500 drugs available for treatment of thousands of health needs, and many thousands more that never made it to market. It would be virtually impossible — not to say financially prohibitive — to test all of these drugs for Parkinson's disease. Where do we start?
Clinical Observation: One source of intelligence on likely candidate drugs for repurposing is simply observation. Say, for example, that a Parkinson's specialist notices over time that several of his or her patients seem to have a slower disease progression. The doctor investigates, and finds that they have one thing in common: they are undergoing the same treatment for cancer. This is in fact what happened in the case of sargramostim (Leukine®), a drug used to boost the immune system in people with cancer. It is now being studied for PD. Observations don't always pan out — they could very well be coincidences — but they can provide clues.
Basic Science Discoveries: Another place to find candidate drugs for repurposing is in the laboratories of basic scientists. Basic scientists study the biological processes that go awry in PD. Sometimes they will learn that a drug on the market already ‘fixes' a problem they may find in PD. This is what happened recently at the PDF Research Center at Columbia University Medical Center (see page 3), when scientists led by Yvonne Schmitz, Ph.D., discovered that in PD, the long arms of the cells, called axons, were damaged. She then identified a compound that could repair axons, and therefore had the potential to be developed into a new treatment. Better yet, she went on to find that a drug already in clinical trials for schizophrenia was very similar to the one she had discovered. The next step is for the schizophrenia drug to be tested in people with Parkinson's.
Population Studies: Another place to find clues is epidemiological studies, in which information is gathered on the health of thousands of people. For example, a few years ago, several studies found that people who took certain medications for high blood pressure, called calcium channel blockers, showed a lower risk of PD. Prompted by this observation, the scientists did more research. They examined some of these drugs for their potential effectiveness in PD, and the outcome was that one of these — called isradipine (Prescal®) — is now in late-stage clinicaltrials for Parkinson's.
Benefits and Pitfalls
Repurposing is clearly an important potential path to new and improved PD treatments. It can save time and money, and uses drugs with well-known risks and side effects. But it has its pitfalls. And without basic research to come up with new potential interventions, repurposing can only get us so far in our quest for new treatments. Here are a couple of the problems:
Inexact: Using a non-PD drug to treat PD could be compared to buying a suit off the rack. It works, but perhaps not as well as a suit that has been custom-tailored. In the best-case scenario, we find that a non-PD drug may ease symptoms of people who live with PD. But it may not be as perfect as a drug that has been designed with Parkinson's in mind.
Look at isradipine, which we discussed on page 6. It is one in a class of drugs called calcium channel blockers that are used to treat high blood pressure. Scientists recently discovered information about the cell biology of PD (see Science News on page 1) that explains why this class of drugs could be very helpful for PD. They also found that while isradipine works, it may not be the best member of this class to treat Parkinson's. There may be a better one.
A Shot in the Dark: In some ways, repurposing is a shot in the dark. For example, if we find that a diabetes drug works for PD, is it clear why it works? Probably not. We can run clinical trials, and maybe even use the drug to treat PD. But it might need finetuning. And until we go back to the drawing board to understand the biology of why it worked in the first place, we cannot perfect it.
The Final Verdict: A Balanced Approach
Is repurposing a shot in the dark or a path to a cure? It is neither. From a scientific point of view, it is imperfect and imprecise. It is not likely that this approach alone will lead us to a cure, or to a blockbuster drug. But from a practical and economic point of view, it is needed.
And for the millions of people worldwide living with Parkinson's, being able to find a good drug on the shelf now is an important interim option while we work to come up with that perfect drug of the future.
We do not have to make a choice between these two types of research. We can use them together — repurposing the good drugs of today while at the same time investing in the even better drugs of tomorrow.
Dr. Beck is Vice President, Scientific Affairs, Parkinson's Disease Foundation.