National Parkinson’s Awareness Month Interview with Robert Edwards, M.D.

Seimi Rurup
April 24, 2018

Parkinson’s disease (PD) is a chronic, degenerative neurological disorder that affects roughly one in 100 people over the age of 60. With no biomarker or objective test to make a definitive diagnosis, PD has kept researchers searching for clues on how to treat, and hopefully prevent, the disease.

April is National Parkinson’s Disease Awareness Month, and so we sat down with Dana Alliance for Brain Initiatives member Robert Edwards, M.D., who specializes in the treatment of PD at the Parkinson’s Disease and Movement Disorders Clinic. Edwards is a professor of neurology and physiology at the University of California, San Francisco. His lab has received international recognition for demonstrating that vesicular monoamine transport protects against MPTP toxicity, suggesting an important mechanism that may also protect against Parkinson’s.

Robert Edwards, M.D.

Regular exercise is proven to have positive effects on gait speed, strength, balance, and overall quality of life for people with PD. Though studies are still limited, dance therapy is said to greatly improve quality of life for this group, even more so than typical exercise. Can you talk a little bit about this?

RE: I am not an expert in this area, but exercise has clear short-term effects on function and for those more severely affected, on quality of life—those earlier in the disease are doing pretty well in any case. Presumably, exercise helps by improving the function of the basal ganglia circuitry that controls movement, much as it would in normal individuals. Dance therapy focuses on balance and other aspects of motor function different from standard exercises, so might be expected to add something new.

The big question with any kind of exercise is whether it affects the underlying degenerative process. Some studies have shown longer-term effects that substantially outlived the exercise itself. But again, this may simply reflect long-term improvement in motor function that would occur with any sustained exercise. There is little clear evidence to suggest that exercise helps the underlying degenerative process, which is our ultimate goal in treating and even preventing Parkinson’s disease. That will require something new.

Besides exercise, are there other lifestyle changes that can aid in slowing the underlying degeneration of PD?

There are some things that we do not recommend because they carry their own morbidity. For example, it has recently been found that high uric acid levels seem to protect against Parkinson’s disease, but we do not usually recommend trying to raise uric acid (through diet or medication) because it is also associated with gout. On the other hand, some organic pesticides such as rotenone can produce a model of Parkinson’s disease, so you might want to stay away from those—they are sold widely, and you can just look on the contents to see if they are present. Other than that, there is not too much else to do because we do not know what really causes Parkinson’s—once we know that, we will be able to intervene much more effectively.

Symptoms of Parkinson’s can often be similar to those of other neurological conditions, which causes a high rate of misdiagnosis—an estimated 25 percent. What distinctions should people be aware of?

There are a range of other neurological disorders that can resemble PD, but a good neurological exam can distinguish many of them, such as essential tremor or more remotely, ALS (motor neuron disease). The ones difficult to distinguish are closely related disorders such as Multiple System Atrophy, Progressive Supranuclear Palsy, Corticobasal Ganglionic Degeneration and Lewy Body Dementia, which is basically a variant of PD, involving very similar pathological changes in the brain, but in different locations.

In many cases, these so-called atypical parkinsonian disorders are not apparent at diagnosis, so patients are labelled as PD. However, failure to respond to L-Dopa, faster progression, and a host of other clinical findings usually arise to indicate a different disorder. Unfortunately, these atypical parkinsonian disorders can sometimes progress more quickly than PD; and it is also more difficult to manage their symptoms. DaT scans can distinguish between some of the more distantly related disorders (ALS) but not those more closely related to PD.

What are the most effective treatments for PD available now? How effective are they?

The current treatments for PD do a good job of managing symptoms early in the disease. In many cases, patients can feel almost entirely normal. As the disease progresses, however, the symptoms become more difficult to treat in several ways: the required increase in medication can precipitate intolerable side effects; some symptoms (such as the gait disorder) can be more difficult to treat; fluctuations develop due to more rapid wearing-off of the medication; non-motor symptoms (cognitive decline, incontinence, hypotension) can be difficult to treat; and sometimes the medication just stops working. Recent developments have helped to manage aspects of these problems: a new long-acting version of L-Dopa helps to reduce medication-related fluctuation; and deep brain stimulation provides a very effective way around intractable fluctuations.

[Editor’s note: See the Cerebrum article, “Gut Feelings on Parkinson’s and Depression” to learn more about the microbiota, which scientists are hailing as a new frontier in neuroscience for its potential in treating a number of disorders.]

Regarding your own research in Parkinson’s disease, what are you most excited about?

I am most excited about the prospect of stopping the progression and better yet preventing the onset of Parkinson’s disease. As indicated above, we have generally effective treatment for symptoms early in the disease, but nothing that addresses the cause of the disease and could therefore slow the underlying degeneration. This is because we do not know what causes it. However, we do know that regular PD involves the protein alpha-synuclein. Mutations in the gene encoding synuclein cause PD, and although they are rare, synuclein accumulates in the brain of essentially everyone with regular PD. What we do not know is what triggers this protein to cause PD, and that is because we do not know what synuclein normally does.

In PD and other degenerative disease, including Alzheimer’s and ALS, a lot of attention has been paid to the way synuclein and a small group of other proteins produce toxicity. Rather than focus on the different forms of toxicity, we are more interested in the origin of disease since that will give us the best option to arrest or prevent disease. This requires knowing the normal function of synuclein and these other proteins, but has proven difficult.

Recently, we found that synuclein normally acts at a particular step in the release of neurotransmitter. In essence, this tells us what the protein is good for and why it might go up, down, or misbehave in disease. Thus, we can work backward from the disease toward its origins and arrest degeneration, potentially before it has begun. This might not require a medication, but something as simple as exercise or diet—we just need to know what kind, and that requires more basic information.

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This year’s awareness month theme from the Parkinson’s Foundation is “Start a Conversation,” which is a call to action that urges people to talk about the disease with their loved ones, neighbors, care team, and community.