New findings by MGH researchers and other scientists are adding to what is known about Parkinson’s disease (PD) and identifying new ways to tackle the disease.
“There is a great deal of work being done that is resulting in new revelations about what causes PD and how it might be prevented, slowed, or reversed, and the exciting thing is that there are so many approaches that the chances are growing that one of them might result in a cure,” says neurologist Todd M. Herrington, MD, PhD, Director of the Deep Brain Stimulation Program at MGH. “Current research is deepening our understanding of PD, and leading to the development of promising new vaccines, genetic approaches, medications, surgical treatments, and other potential therapies.”
WHAT YOU CAN DO
Looking for an exercise program designed with Parkinson’s disease in mind? Contact the Helpline at the National Parkinson’s Foundation at 1-800-4PD-INFO (473-4636) for a referral to a local Parkinson’s-tailored exercise class in your area.
Lack of Dopamine
PD is a degenerative disorder of the central nervous system characterized by progressively worsening motor symptoms, such as slowed movement, rigidity, tremors, and impaired balance, as well as confusion and memory loss. The disorder destroys nerve cells in the area of the brain called the substantia nigra, resulting in a reduction in the production of dopamine, a brain chemical essential to proper muscle movement. The motor symptoms of PD come on gradually, as do other symptoms—such as depression, speech changes, bladder and bowel problems, fatigue and cognitive difficulties.
Researchers have identified hundreds of abnormal genes that are found in the brains of people with PD, but not in the brains of healthy people. Despite this, and the fact that as many as 15 percent of people with PD have relatives with the disease, the genetic link is not very strong in most cases.
“Genetic factors appear to confer a small risk for developing the disease, and the greater the number of abnormal genes an individual has, the greater his or her risk may be,” Dr. Herrington says. “However, single-gene mutations causing PD are rare, and even if your sibling or parent has PD im most cases, your absolute risk of PD increases by only 2-to-3 percent overall.”
Other factors believed to play a role in PD causation include exposure to toxins, such as pesticides and chemicals in well water; the development of clumps of proteins called Lewy bodies, which are found in larger-than-normal amounts in the brain cells of people with PD; and older age.
At this time, PD is considered to be incurable. However, that could change any day, thanks to exciting research activities that are closing in on PD. The following five examples are among many promising approaches:
- Importance of Exercise: Recent research suggests that a lifestyle factor—exercise—may help people with PD slow disease progression and manage their symptoms. A study published in the February 2017 issue of the Journal of Parkinson’s Disease found that people with PD who exercised just 2.5 hours, or 150 minutes, a week had a significantly smaller decline in quality of life and mobility over two years compared to those who did not exercise or who exercised less. Individuals with advanced PD saw the greatest improvements to their quality of life.“It’s not yet clear precisely how exercise produces these benefits,” Dr. Herrington says. “It may be that physical activity helps slow the neurodegenerative process, has a salutary effect on cerebral blood vessels and brain cells, or strengthens muscles and bones to improve resiliency. Exercise might also help promote the creation of new brain cells and connections to replace those that are damaged by disease.”
Experts recommend that people with PD consult their doctors about engaging in exercise, and begin a program of regular exercise as soon as possible to slow physical and cognitive decline and help preserve mobility. (See What You Can Do for helpful information about finding PD exercise activities.)
- The urate connection: MGH researcher Michael Schwartzchild, MD, PhD, is leading a phase-3 trial of a supplement that appears to slow PD progression by elevating blood levels of urate, a salt produced by the body that is derived from uric acid and acts as an antioxidant. People with naturally higher levels of urate are known to be less likely to develop PD. Participants in the study are receiving carefully calculated doses of inosine, a supplement that is converted to urate in the body. An earlier trial showed promising results, according to Dr. Schwartzchild, but “we need to keep cautioning patients and caregivers against using inosine outside of carefully designed trials, since excess urate can cause kidney stones or gout.”
- Deep Brain Stimulation (DBS): A number of exciting new experimental advances are focused on modifying DBS, a treatment option for PD that involves the implantation of electrodes into the brain to reduce the need for drugs. The electrodes are attached by wires to small electrical devices buried under the skin of the chest and can be externally programmed to deliver an electrical pulse to areas involved in uncontrolled movement, reducing symptoms. “There’s been a burst of new technology,” says Dr. Herrington, whose research focuses on DBS. “One technique now being tested involves using ‘current steering,’ a fine-tuning of the DBS device that allows electrical pulses to more accurately target brain areas involved in abnormal activity. Other interesting research is producing DBS devices that are capable of responding to changes in brain activity from moment to moment, and decoding this activity to customize stimulation to fit the symptoms. Finally, new work is assessing whether DBS might be used to address the psychiatric symptoms of PD, such as depression and anxiety.”
- Vaccine: An Austrian biotech company is working on a vaccine that targets alpha-synuclein, a protein that forms into toxic clumps that kill dopamine-producing cells. The drug, called PD01A, is designed to stimulate the production of antibodies that prevent the development of the toxic clumps and/or clear them out to protect dopamine-producing cells. PD01A has produced promising results with few side effects in early trials.
- Gene therapy: A small, preliminary trial has reported success with experimental gene therapy designed to improve the response of people with PD to the dopamine-boosting medication levodopa. Response to the medication tends to decline over time, resulting in a resurgence of motor problems. The experimental technique—in which viruses carry genetic material to convert non-dopamine-producing cells into cells that produce the chemical—appears to have shown promising results.
Any or all of these advances may one day join or replace current treatments. They aim primarily at reducing the symptoms of PD by using DBS or through medications, such as levodopa, the anticholinergic drug trihexyphenidyl, or drugs that mimic the effects of dopamine in the brain or slow its breakdown.