This isn’t a solicitation for a financial donation. But I am going to ask for something valuable that is in short supply and critical to getting an approved therapy to slow the progression of Parkinson’s disease (PD), and move us closer to a cure. It is something you can do to improve the lives of people with PD and take an active role in the Parkinson’s community. Only you have the power to do this.
The discovery that clumping of a misfolded protein in the brain (called alpha-synuclein) causes loss of dopamine neurons and dysfunction in other areas of the brain and nerves that control bodily functions provides opportunities for new Parkinson’s therapies. The research community is excited that preventing this protein clumping process or clearing these toxic clumps may be able to slow or stop the progression of Parkinson’s disease.
However, we still don’t have biomarkers, such as a blood test, that allows us to assess PD progression and test promising therapies in people with PD. Therefore, our best opportunity to test a new potential disease modifying therapy is to see if it can slow progression of PD signs and symptoms in people who were recently diagnosed with early PD and who are not taking symptomatic medications (like levodopa, dopamine agonists, amantadine, or MAO-B inhibitors).
But this poses a difficult challenge! Those diagnosed with early PD based on a combination of bradykinesia (slow and small movement), rigidity (stiffness) and tremor (shaking), can usually only go about six to twelve months before they will want or need medication to relieve symptoms.
Ideally, researchers would like to observe patients in a clinical trial to test a potential disease slowing medication immediately following diagnosis, and for as long as possible. This gives us the best chance of identifying a difference in the rate of progression between those treated with active (“real”) study medication and those treated with placebo. The shorter the testing period, the more difficult it is to identify the beneficial effect of a disease slowing medication. Conversely, the longer the testing period, the more obvious a slowing effect should be.
However, if the proposed time period to test the new medication is too long, many patients will need symptomatic treatment, and researchers will lose their ability to monitor clinical disease progression. Therefore, most trials of potential disease slowing medications in early PD observe patients for about six months to a year.
The key problem is that patients with early PD who are able and willing to enroll in a clinical trial, and whose PD symptoms are mild enough to go up to a year before starting symptom medications are in short supply. To test promising disease slowing therapies, patients with early PD must be identified as early as possible and referred to centers hosting a clinical trial before beginning symptomatic PD medications. Unfortunately, this process fails too often. Patients often wait to seek treatment until their symptoms become troublesome. After all, why see a doctor when you don’t need treatment? However, research-wise it is then too late to participate in an early PD disease slowing trial. Additional unwanted delays may also occur between the time it takes to make an appointment and be seen.
In another disappointing scenario, patients with early PD are diagnosed and immediately placed on symptom medication, even though it’s not immediately required. The doctor may do so instinctively and without considering the lost research opportunity. Of course, immediately beginning medication may be necessary in cases where progression has been swift or if necessary to maintain employment.
The critical time of about one year from an early PD diagnosis until symptom medication is required is called the “Golden Year” for participation in disease slowing clinical trials. It is critical that care providers and patients don’t unknowingly waste this Golden Year.
Therefore, I ask this of care providers and patients:
Care Providers: When you diagnose early PD, please don’t unnecessarily institute symptomatic therapy. Evaluate whether a clinical trial for early untreated PD patients is being conducted within a reasonable distance and discuss the possibility of participating with your patient. At a minimum, let your patient know that there are early PD disease modifying trials being conducted and they may want to learn more about the trials before beginning therapy. Centers conducting such trials would be delighted to discuss ongoing trials with your patient.
Patients: If you have new onset of tremor or slowness, or if a care provider says you may have PD, don’t wait until your condition worsens to the point that you feel you need treatment. Seek evaluation with a specialist as soon as possible. If you are diagnosed with PD, ask about clinical trials. Search online for open trials you can enroll in by visiting ClinicalTrials.gov and Parkinson.org/ClinicalTrials. In addition, if you are diagnosed with PD and your doctor wants to begin medication immediately, consider seeking a second opinion from a center that conducts clinical trials. If you explain that you were recently diagnosed and interested in learning about clinical trials that center will often quickly provide you with an appointment.
Our ability to test promising new potential disease slowing therapies depends on both patients and health care providers understanding the critical value of the Golden Year in PD. I hope that individuals with early PD will consider participating in clinical trials, and the earlier, the better.
The journey to a cure will likely be incremental. If a medication does not work, we want to find out, discard it, and move on to other promising new therapies. Once we demonstrate that a therapy can slow disease progression, we will want to improve on it or find other therapies that can also slow progression and perhaps use them together.
We also need to ensure that clinical trials are designed to meet the needs and priorities of the PD community. This can only be done by working with people with PD to design and implement clinical trials, such as is done in the Parkinson’s Foundation Parkinson's Advocates in Research program. This model of patient engagement in research is being increasingly mandated by regulatory agencies and study sponsors as critical to the research process. Finally, we must be sure study participants and people with PD involved in research represent the diverse PD population to ensure that new treatments benefit the greater PD community. Once we can slow disease progression sufficiently and can identify patients early enough (even before the onset of slowness, stiffness and tremor), the result will be equal to having a cure.
This article was written by Robert A. Hauser, MD, MBA, University of South Florida Parkinson's Disease and Movement Disorders Center, a Parkinson’s Foundation Center of Excellence. Dr. Hauser’s primary research interest is in the development of new medical and surgical treatments for Parkinson's, tremor, tardive dyskinesia, dystonia, and restless legs syndrome.