Old Drugs – New Cures?

From James Beck, Ph.D., Vice President of Scientific Affairs

Using old drugs as new cures seems like a surefire winner. It may be. However, after attending a recent meeting outside London hosted by the Cure Parkinson’s Trust, a small yet impactful British charity, it is clear that this path is neither clear nor easy. A committee of experts at the meeting evaluated and prioritized dozens of existing compounds – many are drugs used to treat other diseases – based upon their potential to stop Parkinson’s disease.

From left, James Beck, Tom Isaacs, and Steven DeWitte at
Cure Parkinson's Trust meeting at Cumberland Lodge.

Repurposing drugs for a new use like this has the potential to shave significant time from the drug development process for Parkinson’s. But existing drugs come with existing problems. And these problems cannot always be overcome. For instance, a recent science article covered by PDF suggested that a chemotherapeutic agent, nilotinib, might be useful for treating PD. However, it is not clear what the proper dose should be (the article suggested a low one would be effective). Moreover, with potential side effects that include sudden death, the committee felt it was not ethical to consider placing people living with PD in potential danger.

Still, there are drugs that appear to be safe and well tolerated, like statins used to lower cholesterol and metformin used for type II diabetes to name a few. These drugs are not chosen at random: By surveying thousands of people, epidemiology studies have been able to link drugs people take for other conditions (like these) with a lower risk of developing PD. There are also data from laboratory studies that suggest how these types of drugs may help. Even here, though, the path forward is not so clear. The mechanism of action, that is how might some of these drugs actually affect PD in people, is not known. This is not always a stumbling block; but when combined with drugs that are likely to have modest effects and low odds of success, it can be a problem, especially with limited resources.

Recognizing these issues, the Trust’s prioritization committee took a hard look at each potential drug candidate and recommended a handful as most promising. These few culled from a list of two dozen compounds will now advance towards evaluation in clinical trials. Hopefully, that phase will begin soon.

Guest Blog: Stroke Story Has Implications for Parkinson’s Treatment

Therapy is most effective when it addresses an individual’s passion 

By Ken Aidekman

Paul West is a professor of English and comparative literature and a prodigious writer of both fiction and non-fiction books. His entire life revolves around words. But, in 2003 he suffered a massive stroke that left him with global aphasia, a condition that rendered him unable to understand words or produce them. His wife, Diane Ackerson, also an author and poet, tells the story of West’s bumpy road to recovery in her book One Hundred Names for Love.

Upon his emergence from critical care, West was faced with the arduous task of regaining his communication skills. Initially, he made reasonable progress, but after a few months of both physical and speech therapy he reached a plateau. Ackerson saw her husband become increasingly frustrated with his failure to achieve more advanced goals. Although his speech therapist asked questions in simple English, try as he might, West could not find the appropriate words to answer her. When he did finally respond, his language frequently included complex metaphors and abstruse literary references. Such answers were lost on the therapist, but Ackerson realized she could parse out her husband’s meanings, albeit with considerable effort.

At this point Ackerson personally took over West’s rehabilitation and re-directed it toward his strengths. She incorporated his extensive knowledge of literature and obscure vocabulary. If he could not call up the exact answer, he was encouraged to get his meaning across utilizing complex word association and phrases from deep in his literary memory. The couple played word games like Dingbats and Mad Libs. They used “immersion therapy” to swamp West with language. When they were too tired to talk, they sang together and exercised together. And when it was all too much they collapsed and fell asleep. Upon waking they would repeat the process all over again.

It took several years, but West’s rehabilitation was a resounding success. He even wrote and published his own book about his experience titled, A Stroke of Genius. The lesson here is that finding the most effective therapeutic approach involves playing to an individual’s strengths. Success or failure in rehabilitating a person with neurological damage may just hinge on appealing to that individual’s unique “passion.”

West did not have Parkinson’s, but the story of his rehabilitation still has implications for those who do. There are therapies that address nearly every symptom of PD. Speech therapy helps with poor vocalization and impaired swallowing. Dance therapy helps with balance and focused movement. Tai Chi promotes body awareness and balance. Vigorous cycling, whether stationary or while riding a bicycle, helps with range of motion and may actually provide some relief from symptoms in general. Exercise and stretching helps keep muscles and joints flexible and strong.

Parkinson’s therapy is a rapidly developing field. Sometimes it seems there are as many different therapies as there are medications. How do you go about finding out which therapy works best for you? Is there a therapeutic mode that fits in with your individual “passion”? Who do you talk to about putting together your own therapeutic action plan?

Your experience provides an important guide for those who are new to the game and less knowledgeable.

What can you share about PD therapies with others that will help them cope?


Ken Aidekman is an investment advisor in Chatham, NJ. Among his activities in the Parkinson's community, he led the Parkinson’s Action Network’s (PAN) efforts in New Jersey to pass the Morris K. Udall Law for Parkinson’s Research and Education. At PAN’s first advocacy forum in 1994 he met Margot Zobel who was in the process of founding the Parkinson’s Unity Walk. Mr. Aidekman helped put together the Walk and became the organization’s first Chair.

[Note from PDF: We thank our friend Ken Aidekman for this thought-provoking blog. We welcome comments below on his post. For additional information on therapies for Parkinson's disease, visit www.pdf.org or contact the PDF HelpLine at (800) 457-6676 or info@pdf.org]

Easing Dyskinesia: PDF-funded Research from 2007 Leads to Testing of Experimental Drug

Earlier this week, PsychoGenics Inc., announced that an experimental drug for Parkinson’s, eltoprazine, seemed to reduce dyskinesia in people with Parkinson’s in early studies.  Dyskinesias are the twisting and writhing movements that occur as PD progresses – a common side effect of the medication levodopa (Sinemet®).   

Back in 2007, it was PDF-funded researcher Manolo Carta Ph.D., along with Anders Björklund, M.D., who performed the pre-clinical research that led to the identification of this drug.  At the time, while many researchers were looking at dopamine neurons as the culprit behind dyskinesias (through their interaction with levodopa), Dr. Carta’s proposal suggested something different – serotonin neurons.  His proposal led to a one-year research fellowship funded by PDF.

After completing his year of research with PDF funding during which he laid the foundation for this approach, he and his colleagues were able to investigate an experimental compounds that might help with dyskinesias.  With the support of other funders, they have now been able to study the effects of eltoprazine in people in this early stage trial – to see whether it is a viable drug treatment.

The study results announced earlier this week indicate positive news about eltoprazine’s potential to ease dyskinesia and possibly some non-motor symptoms of PD.

However, the drug will have to undergo rigorous testing – in additional people with Parkinson’s in phase II and phase III clinical trials – before we know if it’s safe and effective.  While we don’t yet know the fate of this drug, the results help us learn more about dyskinesias so we can find a solution in the future.

PDF believes it’s important to fund ideas like this so that scientists can have both the freedom to explore novel ideas for Parkinson’s and the time they need to gather data that can prove the promise of their ideas.  In Dr. Carta’s work, this proved to be the case. 

We believe this philosophy – funding creativity early on – will help researchers prove their case to other funders that can help them to further develop their ideas ... ultimately into new treatments and a cure for Parkinson’s. 

What are your thoughts? Do you or a loved one need a drug for dyskinesia?

Please share your thoughts below, and as always, call our HelpLine at (800) 457-6676 with any questions you or a loved one may have about Parkinson's.

Why do Promising PD Treatments Fail?

On Tuesday, June 9th, the second day of the Movement Disorder Society International Congress in Paris, Dr. Warren Olanow, one of the world’s leading Parkinson’s specialists, gave a brilliant and authoritative talk on the subject of “What’s New in Parkinson’s Trials?"

His focus was three high-profile clinical trials that have been watched intently and anxiously by people with Parkinson’s around the world.

• One was the Ceregene trial, in which a growth factor called neurturin (CERE-120) was delivered via a gene therapy technique.
• The second was STRIDE, in which a levodopa-COMT inhibitor (Stalevo(R)) was tested for its potential impact on improving dyskinesias.
• The third was ADAGIO, designed to test the potential of rasagaline (Azilect(R)), a PD therapeutic that was approved several years ago to control symptoms of PD, for its potential to actually slow the course of the disease.

Dr. Olanow began his talk by saying that it has been an “extraordinary year …with many new trials involving drugs that offer promise to the patients we serve.” And he concluded it by saying it has been “wonderfully interesting.”

The trouble is, all three trials failed. What does this story mean for PWPs?

To this observer, it means several things:

1. The obvious one is that the intuitive perspective of many clinical scientists is simply different from that of most people with Parkinson's. Studying something, however much one may yearn for it to be successful – as Dr. Olanow does -- is just not the same thing as living with it.
2. Second, it means -- as the speaker himself pointed out in his closing minutes – that we need to do more work in the early stages of the investigative process (e.g., Phase-One trials) to provide greater assurance of efficacy before we proceed to put people living with Parkinson's through the strains and too-often dashed hopes of the much more expensive later stages (e.g., Phase-Three trials).
3. Third, of course, it means, as Ira Shoulson, M.D., another major leader of clinical research and a collaborator with the PDF on several current projects, said to me recently, “clinical research is very, very hard!” Whether it be the imperfections of animal models of Parkinson’s disease, or the data-confounding impact of the notorious placebo effect, or the impact of physician-scientist bias (after all, they too want the trials to succeed!), or simply the immense complexity of defining “end points” – that, is what the measures should be of success or failure, and whether they will be accepted by the FDA – Parkinson’s trials are indeed very hard to do.

There is of course a silver lining to this cloud: that today’s failed trial may be the basis for tomorrow’s successful one.

In at least two of the three trials that Dr. Olanow mentioned, the data have suggested a next step that could have a different outcome. In the Ceregene trial, for example, when the managers went back to see how the trial participants looked three to six months after the trial concluded, they found that some had improved – suggesting that perhaps – just perhaps – the problem was that the trial concluded too early. And in ADAGIO, there does in fact seem to be some neuroprotective effect at lower doses of the drug (though, mystifyingly, not at higher doses), giving some grounds for hope.

In my next post, I will share with you some other things that struck me as interesting about the meeting – including a bird’s eye view of potential new treatments that are currently in the pipeline.