In January 2014, scientists, doctors, patients, and advocates convened at Parkinson's Disease 2014, a conference sponsored by the National Institute of Neurological Disorders and Stroke (NINDS). The goal of the conference was “A cure for tomorrow, care for today,” says conference chair Thomas J. Montine, M.D., Ph.D., professor and chair of the department of pathology at the University of Washington in Seattle.
This is an exciting time for research on Parkinson's disease (PD) and other brain disorders because of the President's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, according to NINDS Director Story C. Landis, Ph.D. The NINDS will use many of the recommendations discussed at the January conference to decide which new research projects to fund. “What would be a real success is a new therapy that slows disease progression,” Dr. Landis says.
Up to one million Americans have PD, according to the National Parkinson Foundation (parkinson.org ). The disease, which destroys nerve cells (neurons) in the brain, causes slowness in movement, stiff walking or “freezing,” problems with balance, and hand tremors when the hands are at rest. No cure exists.
The following are key research goals in PD, according to experts who attended the conference.
No screening test exists to diagnose PD early. Therefore, one important goal is to identify people at high risk of the disease—such as those with genetic mutations, heavy exposure to a toxic substance in the environment (certain pesticides, for example), or accumulations of a protein called alpha-synuclein in their brains—with the hope of prevention. “Identifying people at high risk of PD could allow researchers to focus on delaying its onset,” says Werner Poewe, M.D., professor of neurology and director of the department of neurology at Innsbruck Medical University in Austria.
Researchers are actively searching for biomarkers—telltale biological signs that show up on blood, urine, or imaging tests—that could be used to identify and track people at higher risk of PD. “Ideally, we need a biomarker for PD that changes over time,” says Caroline M. Tanner, M.D., Ph.D., director of clinical research at the Parkinson's Institute in Sunnyvale, CA. For example, if research confirms that a rising level of alpha-synuclein in the brain is a risk factor for PD, a biomarker for alpha-synuclein accumulation over a period of years might be useful in the clinic, much as doctors use increased cholesterol levels to identify an increased risk of heart disease in patients.
Several speakers compared brain accumulation of the protein alpha-synuclein in PD to brain accumulation of the protein beta-amyloid in Alzheimer's disease. However, it is not yet known how important alpha-synuclein will prove to be as a biomarker for PD. The NINDS considers PD biomarkers so important that it funds the NINDS Parkinson's Disease Biomarkers Program aimed at identifying high-risk people, tracking PD progression, and speeding up the development of new treatments, according to Dr. Landis.
The commonly prescribed drug levodopa, which increases the amount of a key chemical messenger called dopamine in the brain, can reduce many symptoms of PD. However, it does not stop the disease from progressing. “We are fortunate to have a number of effective options—including drugs, exercise, and surgical approaches—that relieve the symptoms of PD. But the holy grail is finding an approach that slows the underlying progression of the disease. Nevertheless, we should judge all therapies by their ability to result in meaningful benefits for people with PD,” advises Lisa M. Shulman, M.D., professor of neurology and director of the Maryland Parkinson's Disease and Movement Disorders Center at the University of Maryland School of Medicine and Fellow of the American Academy of Neurology. “We need to include patient-reported outcome measures in research studies. This is are the only way to ensure that the outcome of medical treatments is experienced as a benefit from the patient's perspective,” says Dr. Shulman.
In addition to hoped-for new drugs, one exciting technology for PD patients is deep brain stimulation (DBS), which makes use of an electrode that is surgically inserted into areas of the brain involved in the disease. While DBS can help with movement problems, it does not slow progression of the disease. Scientists need a much clearer understanding of how DBS works before the surgical treatment can realize its promise as therapy for patients. NINDS is currently funding research to determine the safety, reliability, and effectiveness of DBS.
Participants of the conference stressed the need for more clinical studies on the non-motor symptoms of PD such as cognitive impairment and psychosis. Substantial cognitive impairment with PD is called PD dementia or Lewy body dementia. In both conditions, Lewy bodies (protein clumps that are a telltale sign of PD) containing alpha-synuclein are found in abundance in the areas of the brain involved in memory and thinking. Problems with memory and thinking may result in significant disability.
Speakers at the conference discussed in detail the widely hailed promise of induced pluripotent stem cells—which can be made to turn into any cell type in the body—in helping people with PD. Currently, researchers are taking these stem cells from people with PD and coaxing them into becoming dopamine neurons in the laboratory in order to test possible new therapies, says Dr. Landis.
It is likely that research on induced pluripotent stem cell lines will lead to “innovative, personalized therapies,” says Clive Svendsen, Ph.D., director of the Cedars-Sinai Regenerative Medicine Institute in Los Angeles. But he cautions that a great deal of work needs to be done before these cells can be transplanted into the brains of people with PD to treat the disease. One key question is whether the lab-engineered dopamine neurons would communicate like natural neurons in the brain. In theory, if the engineered replacement brain cells behaved like natural neurons, they could restore nearly normal movement for years.
A number of patients and patient advocates spoke at the NINDS conference. Jean Burns, an artist who has participated in 10 clinical trials and co-founded PDPlan4Life.com as a resource for patients, urges people with PD to enroll in clinical research trials. To scientists, she said, “I encourage you to use patients in your meetings; I hope you will remember me and remember to add the patient voice when you have your discussions.”
Linda Morgan, who also has PD, supports participating in clinical research trials and including patients and advocates in the research planning process. She urges scientists to balance their efforts on “long-game research” aimed at a cure for the disease with “short-game research” aimed at helping patients with their symptoms, especially fatigue.
Like Burns and Morgan, advocate Steven DeWitte has PD. He is another strong proponent of participating in clinical research trials. DeWitte started the Clinical Trial Transportation Program by partnering with Beth Israel Deaconess Medical Center in Boston, MA, to help volunteers with PD who lacked transportation participate in research studies. DeWitte participates in a program of the Parkinson's Disease Foundation called Parkinson's Advocates in Research (PAIR). For information on help with transportation needs and other support, go to pdf.org .
Daniel M. Lewis, who has had PD for 20 years and served as chairperson of the Parkinson Foundation of the National Capital Area, stresses the importance of support groups and exercise for those living with a diagnosis of the disease. In the absence of a cure, it's important for everyone who has PD to find ways of improving his or her quality of life, Lewis says. He notes that exercise provided “a dramatic change” for the better in terms of his own health.
Amy Comstock Rick, J.D., CEO of the Parkinson's Action Network (parkinsonsaction.org ), says everyone with a stake in PD research, including patients and advocates, should have a voice in the research agenda. “No research is successful in isolation,” she notes, adding that recommendations coming from the conference should reach as broad an audience as possible, including members of Congress.
To watch video interviews with experts in Parkinson's disease, go to bit.ly/1fyjxzU.
* For more Neurology Now articles on PD, go to bit.ly/1j50Mnz
* For articles on PD from Neurology Today, go to bit.ly/1gqRIZW
* To read Patient Pages on Parkinson's disease (and other conditions) from Neurology, one of the American Academy of Neurology's medical journals, go to bit.ly/1eAj50Y