From the WPC Blog, August 15, 2018:



Tanya Simuni, MD presented at the Fourth World Parkinson Congress in Portland, Oregon and will be presenting at the Fifth World Parkinson Congress in Kyoto, Japan. She is currently a Professor of Neurology and Director of the Parkinson’s disease and Movement Disorders Center at the Northwestern University Feinberg School of Medicine.

Ideas and opinions expressed in this post reflect that of the author(s) solely. They do not necessarily reflect the opinions of the World Parkinson Coalition®


Parkinson’s disease (PD) is a chronic neurodegenerative disease that affects 7-10 million people worldwide. While the cause of the disease remains unknown, tremendous progress has been made in developing therapeutic options for management of PD motor disability. The major area of unmet need remains finding therapeutics to slow or halt disease progression and ultimately to reverse its cause. Such therapies are called: “disease modifying” or “neuroprotective”.

Terminology you should become familiar with:

Neuroprotective: Neuroprotection means that the therapy is able to reduce cell death or salvage damaged neurons. We are able to reliably measure neuroprotective effect in animal models and in cell cultures. In order to make such determination in PD patients, we need to have reliable ways to measure cell counts or cell function in a living person, which remains a challenge. For that reason, clinical trials usually measure ability of the intervention to slow disease progression based on a clinical scale or other clinically relevant outcome measures. For that reason “disease modification“ is the preferred terminology for clinical trials. It is the hope that disease modifying intervention does truly impact and slow the process of neurodegeneration.

Biomarkers: Biomarker is a “measurable indicator of some biological state or condition” (Webster dictionary). The key is that it is objective, reliable and reproducible. A perfect example of a biomarker is blood sugar level as an indicator of diabetes or cholesterol level as a risk factor of cardiovascular disease. Biomarkers are essential for screening of the population at risk (disease trait) or for monitoring disease progression (disease state). One of the areas of major unmet needs in Parkinson’s is lack of such objective biomarkers.

History of disease modifying trials in PD: There has been a tremendous effort to develop disease modifying interventions in PD. Over the last three decades multiple drugs have been tested in different phases of clinical trials and none have been successful. What are the reasons for failure? As outlined in Dr Stoessl’s blog dated June 18, 2018, there are multiple factors. We still do not know the cause of PD. Our animal models that are used for drug screening are not reflective of humans’ Parkinson’s disease, we lack biomarkers of PD progression, and we might be using not sensitive enough outcome measures, to name a few …

So now that I have outlined all the challenges, why do I remain optimistic (aside from being an eternal optimist)? I believe that the discoveries of the last decade better our understanding of the mechanisms underlying the disease: PD genetics, ways to screen out less than promising therapeutics, all bring us to the next level of drug discovery. Below are a few examples of most promising therapeutic targets:

α-synuclein targeting therapies: α-synuclein is a protein that accumulates in the cells of people with PD. α- synuclein is a normal constituent of cells, but in the disease state there is pathological aggregation of the protein, failure to clear it effectively from the cells, and potentially propagation from cell to cell. All these changes lead to cell dysfunction believed to be essential in the mechanism of PD development. For these reasons there is tremendous effort in development of α–synuclein targeting therapies. There are a number of different α–synuclein targeting approaches in various phases of development. These include ways to reduce α–synuclein production, intracellular aggregation, increase intracellular and extracellular protein degradation and reduce extracellular propagation. Of these, α–synuclein targeting immunotherapies are most advanced in the clinical trials. The target of these therapies is reduction of extracellular α–synuclein by way of either active vaccination (ClinicalTrials.gov Identifier: NCT02267434) or passive immunization by intravenous administration of antibodies. Two companies are currently testing the latter approach in early phase clinical trials (Roche, ClinicalTrials.gov Identifier: NCT03100149)and Biogen (ClinicalTrials.gov Identifier: NCT03318523). Both agents had extensive preclinical testing and an acceptable safety profile in Phase I studies. While we have to be cautious regarding promises of success, especially with failures of similar approaches in Alzheimer’s disease, these are exciting therapeutic targets tackling underlying disease biology.

Therapeutics aimed at specific PD subtypes: We are well aware that the clinical course of PD can vary substantially among different patients even with a similar age of onset and disease duration. There is a tremendous effort to better understand the biological underpinnings of PD heterogeneity. One obvious target is the subset of people with PD (PwPD) who carry a specific PD related genetic mutations. While a minority of PwPD carries a single PD relevant genetic mutation, these can teach us a lot about PD mechanisms at large. GBA and LRRK2 are two most relevant mutations with therapeutics already in clinical trials.

GBA targeting therapeutics: Glucocerebrosidase is an enzyme essential for normal function of the part of the cell called lysosomes that are responsible for the clearance of proteins and thus assuring normal cell function. The function of the enzyme is coded by the glucocerebrosidase gene (GBA). People who carry two copies of the abnormal gene develop Gaucher disease, the most common lysosomal storage disease. Interestingly, it was noted that people who carry only one abnormal copy of the gene do not develop Gaucher, but are at higher risk of development of PD. In fact, GBA is not considered the most common genetic risk factor for PD. The relationship between GBA and PD is linked to an inverse relationship between lower levels of glucocerebrosidase enzyme and increased levels of α–synuclein and vice-versa. Due to this relationship, GBA targeting therapeutics are believed to be potentially effective not only in GBA mutation carriers, but also in people with sporadic (no genetic mutation) PD. A number of different therapeutic approaches are in development including ways to increase enzyme production, improve the function of enzyme and reduce the substrate for the enzyme (in a way to reduce the work load for the enzyme). The therapeutic that is most advanced in clinical trials is developed by Sanofi (ClinicalTrials.gov Identifier: NCT02906020) testing substrate reduction approach.

LRRK2 targeting therapeutics: LRRK2 is the most common autosomal dominant mutation associated with PD. While the most common, it is still rare in the general PD population, ranging between 1.5-3% and more common in selected ethnic groups. The role of LRRK2 kinase in PD is still not fully elucidated, but multiple convening lines of evidence indicate that reduction of LRRK2 is associated with neuroprotective effect in PD animal models. A number of companies are working on LRRK2 targeting therapeutics though none of them so far have been tested in PwPD.

In conclusion, the new generation of potential disease modifying therapies in PD are being developed based on the latest scientific discoveries, with much higher vigor in selection of preclinical targets, assuring that the drugs actually reach the brain targets they are supposed to work on and targeting genetic subtypes of the disease. All these are the reasons for my optimism though the challenges still remain. It should be recognized that disease modification is the most challenging treatment target across neurodegenerative disease. In the interim, PwPD should remain active contributors to the drug discovery process including active participation in clinical trials.

What we Wish We Had Learned at the Beginning

Contributed by support group members Rick and Arlene Pincus, posted April 2018

A diagnosis of Parkinson’s is not always followed by patients learning what they need to know to live the best lives they can and participate effectively in their care.

What follows is an incomplete list of information we wish we had learned over the first few weeks.

1. Parkinson’s patients should be followed by movement disorder specialists, not just internists or neurologists who do not specialize in Parkinson’s.

2. Sinemet is diagnostic. A therapeutic response to it this medication confirms the diagnosis. (However, patients who do not respond to Sinemet may have an atypical form of Parkinson’s. Lack of response requires further analysis by a movement disorder specialist who can determine if the patient has atypical Parkinson’s or the trouble is something else.)

3. Sinemet, often, but not always, is the first medication a Parkinson’s patient is prescribed. It does not become less effective over time, even though some believe this. The disease progresses, and therefore, patients come to need a larger dose.

4. Parkinson’s does not destroy automatic reflexes. Someone with Parkinson’s will continue to hit the car’s brake when red lights appear ahead. It is voluntary movement that is affected. Other automatic responses will continue to be normal, too. (E.g., blinking in response to intense light or having an object approach the eye.)

5. Parkinson’s affects muscles, including those we do not observe. It affects vocal cords (and therefore both speech and swallowing). Patients trained to properly exercise their vocal cords do better than those who make no such efforts. Speech therapists are critical for analyzing both speech and swallowing and observing how the patient is functioning at diagnosis. Speech practitioners make appropriate recommendations and teach patients how to maintain full-throated speech and how to avoid swallowing problems that can lead to serious medical conditions. (And there’s an APP for monitoring your speech practice!)

6. Constipation can occur because Parkinson’s changes how the bowel behaves. Your doctor can recommend appropriate interventions and make life more comfortable.

7. Physical therapists can analyze functioning at diagnosis and teach patients what work they can do to maintain function. Physical therapists can address gait, posture, and balance and teach patients how to maintain function and protect themselves. Falling is a true risk, and waiting until falls are a problem is not the best approach. (Same goes for occupational therapists, who can help patients set goals with respect to completing tasks that were once automatic and uncomplicated.)

8. With a proper referral, speech, occupational therapy, and physical therapy are covered by most insurance.

9. Although there is a “Parkinson’s pain syndrome,” no patient is immune from other medical problems. A movement disorder specialist can determine if pain is a result of Parkinson’s or if other conditions are in play.

10. Exercise really matters. People who are in good physical shape at diagnosis have a leg up. All Parkinson’s patients should be involved in appropriate exercise programs, and their doctors and/or their physical therapists can recommend options that are safe and effective.

11. Parkinson’s patients’ symptoms vary. Individuals can experience a variety of symptoms even within a single day. Even a movement disorder specialist might not choose the most effective medication or the perfect dose and dosing schedule the first-time medication is recommended. Taking good notes and providing the doctor with these will go a long way to achieving the best possible response.

12. Although Parkinson’s is a progressive disease, patients who are provided with interventions that match their needs and capacities have been known to make improvements.

13. Some patients are candidates for Deep Brain Surgery (DBS). (LINK HERE) Originally, it was thought that DBS should be reserved for when patients were older. Newer thinking is that DBS does not stop working (although batteries need replacing in the same way that pacemakers require battery changes.) Presently, many physicians think that the younger and healthier the patient, the more benefit might be gained and for more years. Only a team that includes a movement disorder specialist and a surgeon, and other adjutant professionals (e.g., a psychologist) can determine if patients are appropriate candidates for DBS. Programing DBS is tricky; there is no manual that prescribes exactly which of the many settings will work for any patient. A talented programmer (a neurologist) and a patient who provides useful feedback will still need to try multiple settings to find the one(s) that work best for each individual. DBS can reduce the amount of medication required, reduce tremor, and lesson or aggravate non-Parkinson’s involuntary movements (dyskinesias). It has also been known to lessen dystonia and even provide settings at which a patient’s speech improves. There are risks that make careful evaluation necessary before this step is offered.

14. Parkinson’s is not a once size describes all disease. Even medication recommendations that advise separating food from medication intake do not apply to all patients.

15. Support for both patients and those who are involved in their care is very helpful. Fine support groups exist, and individual care (e.g., psychologists) might be indicated as well.

PD hallucinations v.posted.pdf

Your Super Power

By David Higgins, January 10, 2018

Growing up as a kid some of my earliest memories were of my grandmother’s struggle with Parkinson’s disease. It was difficult for her to walk - she shuffled with great labor - and there were many awkward moments when she would talk to me and I couldn't understand a word she was saying. I did a lot of guessing at an appropriate response.

It may seem like a strange memory to have of your grandmother, but I’ll always remember her love for atomic fireballs – those hot, red, round, individually wrapped hard candies. She is the only person I’ve ever known that could actually keep one in her mouth the whole time it took the outer hot layer to dissolve. Maybe THAT was my grandmother’s super power!

She kept a supply of fireballs in a drawer in her dining room. I remember how, without a word, she would struggle to rise from her chair, shuffle with great difficulty across the living room and into the dining room. She would spend several concentrated minutes opening the oversized drawer of the buffet that resisted her every tug. At last - fireballs revealed! She would painstakingly fish one atomic fireball out of the drawer. Grasping the fireball as if it were a prize, she would repeat in reverse the process of closing the drawer and returning to the living room, shuffling and holding on to the walls as she made her way toward me. She would hand me the candy and mumble something I couldn’t understand. Nothing about her expression gave away anything she was thinking or feeling. Her Parkinson's mask was firmly in place.

This is the only way I ever knew my grandmother. I knew she had Parkinson's disease, but only as a person living with Parkinson’s myself have I come to appreciate what cruelty it can impose. Now I understand that she was showing me she cared by giving me one of her prized atomic fireballs, sharing her simple passion and performing a feat that for her demanded great effort. She was conquering Parkinson's in her own way, as best she could. In spite of her disease she was living life largely on HER terms. Surrounded by family, showing a grandchild she loved him. THAT was her super power!

Parkinson’s is a quality of life disease. It can take away everything it means to be human, every aspect of your life that you think of as living: your ability to walk, talk, smile, think clearly, drive, dress yourself and eventually even to eat. It will challenge the relationships with those around you, test your loved ones with unfair demands, and make carrying out simple acts of daily living a super power.

We all have a super power. Ours, here, today, is to be doing exactly what we’re doing: Making a difference in the lives of people living with Parkinson's disease.

Coming Out as a PD Patient

By Rick Pincus, November 19, 2017

I had the most difficult time “coming out.” I was diagnosed at 60 and didn’t tell anyone at work until I put in for retirement five years later. I had few visible symptoms and became very adept at concealing those. I don’t know why I instinctively held back from telling people, but the feeling was quite strong and extended beyond the workplace.

My late mother-in-law was still alive and a fuss-pot worrier. My wife was rightly convinced that every phone call would be an interrogation about my PD. We never came out to my mother-in-law, who lived 10 more years and continually pressed us for why I seemed different. We lied.

On some level I convinced myself that people would see me as Mr. PD and ignore who I am. You are your disease would be the attitude. The first time I came out was to my granddaughter.

She was a student in the school where I was a librarian. It didn’t feel right to make her be a guardian of my secret. Still, it finally felt right when we made our first trip to look at colleges. Rachel and I flew from New Jersey to Portland, Oregon. We were visiting my alma mater, Reed College. It was the first night of the trip.

We had just had dinner and were sitting in the lobby. I said, “Rachel, have you noticed that I have a tremor in my right hand?

She said that she had. “I have Parkinson’s Disease.”

“Are you going to die, Grandpa?”

“Not for a long time.”

She asked a few more questions about PD and asked why I was keeping it a secret. I realized that I didn’t have a very good reason, so I blamed it all on my mother- in-law and we moved on.

I spent the next year in the closet, figuring that most people wouldn’t handle the news as well as Rachel had. There didn’t seem to be any way to broach the subject.

Some People did ask me if something was wrong, that pesky tremor again. I passed it off on to a pinched in my neck, which I do have.

It wasn’t until we moved to San Diego in January of 2012 that I openly admitted that I had PD. It had seemed shameful, making me feel as if I were a leper. I don’t know where that came from. Yet, I found that other PD people had similar feelings. I sure would like to know what you, dear readers, went through in your journey from diagnosis to public person with Parkinson’s Disease.

Well, wouldn’t you know, just as I was about to wrap this column up, Jesse Jackson announced he had Parkinson’s and had hesitated in going public. Remember Michael J Fox’s long struggle to keep his PD secret.


Write me, Rick Pincus, at repincus@gmail.com and let’s get this conversation started.

Please indicate in your email whether you are just telling me, or you are inviting me to quote or summarize what you have to say (and with or without your name) so that I know not only how you feel and what you think and also whether what you write to me is private or for all our readers.


By Sharon Jones, November 17, 2017

In honor of Thanksgiving, many of us give thanks during November. But we really should be expressing gratitude on a daily basis.

Numerous scientific studies have shown the health benefits of gratitude, including one done in collaboration with University of California, San Diego (UCSD) and the University of Sterling, Scotland. That study, published in the Journal Spirituality in Clinical Practice, assessed the role of gratitude in wellbeing among asymptomatic heart failure patients. Its results suggest that a simple gratitude exercise may benefit these patients.

As study author Paul Mills, a UCSD professor of family medicine and public health, explained: “We found that those patients who kept gratitude journals for those eight weeks showed reductions in circulating levels of several important inflammatory biomarkers, as well as an increase in heart rate variability while they journaled. Improved heart rate variability is considered a measure of reduced cardiac risk.”

At a recent support group presentation, I asked J. Vincent Filoteo, PhD, a psychologist on UCSD’s movement disorder team, if gratitude was being studied in relation to Parkinson’s. He didn’t seem to know anything about scientific studies in relationship to gratitude’s health benefits.

I found this surprising. Many studies on treatments of Parkinson’s have demonstrated the power of the placebo affect. Patients who believe they are receiving treatment (but actually aren’t) show improvements equal to those receiving the treatments. Clearly the beliefs and thoughts of PwP affect how the illness progresses. If a gratitude journal benefits heart patients, certainly it would benefit PwP.

If you want to learn more about the power of gratitude, follow these links:

For All Parkinson's Disease Patients

By Katy Searles, November 8, 2017

I feel motivated to write about something that I'm passionate about (as many of you know) and that's maintaining a positive attitude. I remember in the August meeting of the Mission Valley group that the stem cell doctor talked about the placebo effect being real. I believe it is. To quote from Brain Storms by John Palfreman, “while medicines may be false, the placebo responses going on in our brains must be real, mediated by actual neurotransmitters. It's not mind over matter...it's coming from dopamine.”

So this means to be that so much of PD is about mindset, and if we keep a positive attitude, exercise (which we now know produced dopamine) and live our lives to the fullest (despite Parkinson's) we can defy PD. The placebo effect is a double-sided coin, however, and if we feel victimized and downcast and believe everything is negative, etc., guess what the result will be. I urge all my friends in our support groups - DON'T GO THERE – you'll be harming yourself, no kidding.

When you hear horror stories about scary symptoms that can happen with PD like hallucinations, etc., don't take it personally. Rather take it as information about the disease that can happen, but not necessarily to you. If difficult symptoms of Parkinson's happen to you, deal with them then – if and when they show up – not before. There's nothing you can do before they show up anyway, except worry and get depressed. Trust that your doctor will know what to do if difficult symptoms show up. Don't ruin what good feelings you can have today by worrying what may or may not happen tomorrow. That's CRAZY! Have as much fun as you can while you can. Who knows – some people say laughter and having fun produce more dopamine. Might as well give it a try, in my OPINION.”

The Invisible Patient

By Rick Pincus, October 29, 2017

When did I first realize that I had become invisible?

It was recently, in a UCSD office, where a tech who did not usually work for my movement disorders neurologist addressed my wife instead of me.

The assistant had been taking down my recent history. Arlene was supplying as much of the information as I was. It seemed to be a three-way conversation. Then the assistant hauled out her sphygmomanometer. It was blood pressure reading time, and I was about to go invisible.

She turned to Arlene and asked, “Does Richard prefer one arm over the other?” Arlene answered for the first of many times, “Ask him he’s right there…and he talks.” The tech replied, “Oh, I know that. It’s just that Parkinson’s patients are sometimes more comfortable if their caregiver talks for them”

I put in my two cents worth: “It might be more sensitive to ask the patient first.”

There was a flutter of words and the matter was settled for that moment. But…

It keeps happening. PD makes us invisible. We need to be seen. This is our responsibility as Parkinsonians. When even one of us accepts invisibility, it makes it harder for all of us to take control of our treatment, our meds, our lives. It sometimes feels good to be taken care of, to let other people make decisions, transport us, make receiving care our reward for suffering from Parkinson’s.

Yet if we let other people act for us when it is unnecessary, we contribute to other people’s tendency to disregard us in favor of turning to anyone we might have along, possibly even someone who has no real clue about what we need. It is only through each person’s fullest possible participation that we can live in true dignity and be recognized as functioning adults. None of this is possible if we allow ourselves to be invisible. It is as simple as waving a hand and saying, “Yoo-hoo, Doctor, I am over here.”

This is why I go to Rock-Steady boxing 4 or 5 times a week. It is why I fight to overcome my considerable shyness. It is why I have agreed to write this column.

Chronic diseases, in general, lead many to see the disease and not the person. We are not our disease. We are merely human beings who have a condition that will only be more bearable if we are own best advocates.

So, take a pad and pen to your next appointment. Bring notes take notes and ask questions. Keep calling for the focus to be on you. Do it for yourself, and do it for me. Support groups exist for only a couple of hours a month, but we support each other each time we insist on being visible.