VAI Voice

The Official Blog of Van Andel Institute
10 Apr 2018

Revealing the “hidden face” of Parkinson’s: A Q&A with Professor K. Ray Chaudhuri

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When British surgeon Dr. James Parkinson penned the first medical account of the disease that would come to bear his name, he described more than the condition’s hallmark movement-related, or motor, symptoms.

Interspersed in his case reports are mentions of other seemingly unrelated afflictions such as pain, difficulty sleeping and constipation. Though brief in nature, they foreshadowed a shift in our understanding of an often inexplicable disease.

Now, 200 years after Parkinson’s Essay on the Shaking Palsy was published, these non-motor symptoms are changing the way we study, understand and treat Parkinson’s. They may also be the key to unlocking many of its secrets, including how it begins.

For the past two decades, Professor K. Ray Chaudhuri has been at the forefront of this field. An international authority on non-motor symptoms of Parkinson’s, his work greatly expanded our understanding of the disease and reinforced the importance of addressing non-motor problems to improve quality of life for people with the disease.

He is a professor and consultant neurologist at King’s College Hospital in London and is the medical director of the Parkinson’s Foundation International Centre of Excellence at King’s College. Professor Chaudhuri has earned numerous accolades for his contributions to science and the Parkinson’s community, including the Royal College of Physicians London Award for Outstanding Research Leadership.

We chatted with Professor Chaudhuri about the importance of understanding and treating the non-motor symptoms of Parkinson’s and where he sees treatment going in the future. You can also hear from him at Grand Challenges in Parkinson’s Disease Sept. 26–27 at Van Andel Research Institute, where he will receive the 2018 Jay Van Andel Award for Outstanding Achievement in Parkinson’s Research.

Please tell us about your work. How did you get interested in your field?
I have always been interested in what I call the “hidden face” of Parkinson’s. We are all concerned with motor problems in Parkinson’s — tremor, rigidity, gait, bradykinesia — but I also noticed that if you read James Parkinson’s original description of the disease, he details many other symptoms in these patients, such as pain, sleep and autonomic problems, constipation and delirium. Yet, for a long time, we as a specialty never really concentrated on taking these symptoms together as a whole.

Professor K. Ray Chaudhuri

In the last 20 or so years, my research has largely focused on developing and recognizing the range and nature of these non-motor symptoms of Parkinson’s — the hidden face — and figuring out what we can do about it. I have been interested in the whole, big picture, not just focusing on individual non-motor symptoms. This is because the patient comes to us with a complex medley of symptoms,  not just individual symptoms.

We have established that you can actually measure these symptoms at the bedside; one can make “holistic” scores that change after treatments and as such can be monitored. You also can develop biomarkers for these symptoms and you can even try generating good animal models for them. By using these tools, you can measure, and measurement is crucial for developing treatments as well improving care and delivery of health care. That is important because the burden of these non-motor problems drives quality of life for patients and their families.

How has our understanding of non-motor symptoms in Parkinson’s changed in the past two decades?
I think we have a much greater understanding of non-motor problems and their impact on people with Parkinson’s. More importantly, patients are more aware of them, patients are driving research into these symptoms, and patients are also asking their doctors, “Can you do something about these non-motor problems?”

Are there symptoms we now consider related to Parkinson’s that we didn’t consider related to the disease 20 years ago?
I think it’s more of an awareness of the problem. These symptoms have always been there. A key area of understanding is that not everything in Parkinson’s is related to dopamine — you can have other neurochemicals involved; for instance, cholinergic chemicals, which can drive problems such as dementia and apathy, and serotonergic and noradrenergic chemicals, which can drive sleep problems and autonomic problems, such as dizziness.

There also are medication-induced non-motor problems, like hallucinations and so on. Then you even have the rare group of patients who might have specific genetic mutations and who, as a result, might express particular non-motor problems. An example is the GBA gene mutation. In these patients, we now know that there is a higher risk for cognitive impairment such as cognitive dementia.

The other thing we now know is that the reason that most neuroprotective treatments don’t work is because they’re started too late. By the time a patient develops tremors or bradykinesia — the typical motor symptoms of Parkinson’s — they may have had the condition for five, 10 or 15 years. In many situations, the initial problem might have been a reduced sense of smell or a sleep dysfunction we call rapid eye movement behavior disorder. These problems begin years before the symptoms of Parkinson’s that we traditionally recognize start, but because we rely on motor symptoms only to initiate treatment, we are starting so-called neuroprotective treatment late. That is another area where our understanding of Parkinson’s has changed.

Is a better understanding of non-motor symptoms helping people get diagnosed earlier?
There’s a long way to go still. These problems, such as reduced sense of smell, can occur in the general population as well. However, we now know that if you have reduced sense of smell for no other cause — such as an accident, a head injury or bad rhinitis — and suddenly your sense of smell is gone or reduced and on top of that you have sleep dysfunction, the two together makes it quite likely that that person will go on to develop Parkinson’s.

How does a better understanding of non-motor symptoms in Parkinson’s impact research and treatment?
It’s the burden of non-motor symptoms that really drives quality of life in Parkinson’s. You can improve a patient’s tremor and rigidity by administering treatments that we already have, but that patient might still be deeply unhappy because he or she is in pain, they’re depressed, they’re anxious, they might have sleep problems, they might have apathy, their personality might change — these are all non-motor symptoms in Parkinson’s.

We need to move away from this very old-fashioned view that treatment of Parkinson’s can only be done by dopamine-related therapy. Instead, we need to think about Parkinson’s treatment in a more holistic manner and start using personalized treatments like we do for many other conditions, like multiple sclerosis, diabetes, breast cancer or Hodgkin’s disease.

Parkinson’s is exactly the same as these conditions — no one size fits all. We need to be more individualized; we need to assess relative risk factors for each patient, and then we need to expand on that and provide treatment appropriately.

In some patients, for instance, there might be a high risk that if you give a dopamine drug, the person might fall asleep while driving. For this particular group of patients, we should have a system that recognizes this particular subtype and leads us to avoid certain dopaminergic drugs. In another group, we know they have a high risk of memory issues and cognitive problems so in those patients, we should avoid drugs that enhance memory problems and perhaps start memory enhancing agents. In other patients, we know that the stomach absorption of Parkinson’s drugs is very limited; if we recognize this early on, we can use non-oral therapies because administering oral drugs to a patient who can’t absorb the drug properly is going to be largely useless.

This is how we should shift our paradigm. It’s not so much discovering new drugs because levodopa is still our best option and it was discovered in the 1960s. It’s more about how you administer treatment and how you consider the whole aspect of Parkinson’s — only then can you deliver true personalized medicine.

What should a person who is newly diagnosed with Parkinson’s know about non-motor symptoms?
It’s very important to try to use biomarkers to assess these patients individually and decide for each person what the trajectory of their Parkinson’s is going to be. This is not absolutely accurate at the moment but I believe we will come to a stage when we can do this properly in the future, which will lead to better individualized plans for each patient.

We need to tell patients that some of the problems they’re experiencing, such as sleep problems or fatigue, are actually part of Parkinson’s so they don’t get sent to different doctors and treated for other diseases when their symptoms can be managed as part of Parkinson’s.

We also must reinforce that many of these symptoms are treatable. We did a study a few years ago, and 40 to 50 percent of patients never discussed non-motor problems during their primary consultation. Many of the problems that were later identified in these patients can be treated — you can manage depression, you can manage anxiety, you can manage pain — but if it’s not discussed, we don’t know to treat it.

The reasons why it was not discussed were, first, the consultation doctor didn’t have enough time; second, the patient didn’t know that these symptoms might be related to Parkinson’s; and third, some patients found it very embarrassing to discuss. In younger patients, for instance, sexual dysfunction or dribbling of saliva is not something they want to talk about but the fact is if you do discuss it, we can treat it effectively and hugely change their quality of life. All these issues are important to discuss openly when patients are diagnosed.

Where do you see Parkinson’s treatment going in the next five years? 10 years?
I think treatment is going to become more holistic and rely more heavily on medications that work on multiple different sites in the brain. Parkinson’s affects so many different systems and that’s why levodopa is still the best drug because it works on multiple pathways.

We also will probably have more precision and personalized medicine thanks to improved delivery methods for drugs and a better understanding of genetic and other mechanisms, which can be targeted for treatment. An example is mutations in GBA genes. Drugs that affect the GBA pathway might be curative for patients who carry the gene. If they do not yet have symptoms and take such a drug early enough there may be a possibility that it might stop the disease or delay the development of Parkinson’s.

We need to focus on the gut as this is emerging as an important area for management of Parkinson’s. Then there also is the role of complimentary therapies. We need to understand these better in properly controlled trials and studies.

Would you like to hear more from Dr. Chaudhuri? Please join us for Grand Challenges in Parkinson’s Disease Sept. 26–27, 2018 at Van Andel Research Institute in Grand Rapids, Mich., where he will give a talk and receive the 2018 Jay Van Andel Award for Outstanding Parkinson’s Disease Research. For more information on Grand Challenges and to register, please visit grandchallengesinpd.org.