Parsing Parkinson's

APRIL 25, 2017 PARSING PARKINSON’S

Parkinson’s disease is characterized as a movement disorder identified by specific physical and cognitive characteristics. No biomarkers have been identified that determine whether or not a person has Parkinson’s. Often dementia-causing Lewy bodies are discovered in the brain at autopsy. Autopsy is not the most effective way to identify a disease.

After living with the PD diagnosis for nearly 10 years, I have a theory about Parkinson’s, and a suggestion about a research path to pursue. First, it is clear to me that Parkinson’s is a name for a group of diseases, much as “cancer “is the word that lumps multiple subsets of that disease. Cancer has breast, prostate, liver, pancreatic, skin, etc. etc., all forms of cancer with some common characteristics but differentiated by specifics and by treatment modalities. Similarly, the term “Parkinson’s” identifies a class of diseases, not a single entity that can be treated with one approach. It is no wonder that research trials consistently fail when they test a one size fits all application.

From my perspective, as one who lives with an iteration of the disease and who has many friends who live with various forms of it, I see manifestations as: tremor dominant and non-tremor dominant; early onset (before age 55) and normal onset (average age about 62); genetic and idiopathic, cognitively intact and cognitively challenged. Some people endure multiple physical challenges in walking, balance, bowel function, nausea, etc. Nearly everyone loses their sense of smell, ability to write normally and speed of movement and nearly everyone suffers from anxiety.

Treatments are all over the map. For over 50 years levodopa has been the gold standard drug. Deep Brain Stimulation (DBS) seems to be most effective for younger people with tremors. Dopamine Agonists, marijuana, “natural remedies”, and special diets each have their passionate followers. Exercise is the new medicine, especially high cadence cycling, but other exercises show promise as well and each has its following.

I think researchers will eventually catch on to the idea that one treatment won’t serve everyone, and the more they carry out large research studies without differentiating the PD population, the longer they are doomed to finding no single cause and no definitive cure or effective remediation of the diseases, because there IS no ONE disease; there are MANY.

This insight is the result of my very specific personal experience. Diagnosed in 2008, I learned about Forced Pace Cycling research done by neuroscientist Dr. Jay Alberts of the Cleveland Clinic. I signed up and by cycling far beyond his protocols, was able to effectively rid myself of the disease enough to enable me to ride my bike across Iowa six times, climb Mt. Kilimanjaro, and accomplish other unlikely feats for a woman in her late 60s. Despite my success with cycling, the disease continues its inexorable march through my body and mind.

In early 2017 I read about a Phase I study, the Stanford Parkinson’s Young Plasma Study, in which older PD patients would be infused with eight units of plasma taken from 18-25 year old males. This treatment idea was following up on research done with rats and Alzheimer’s patients that showed cognitive and motor improvements with such infusions. I immediately contacted the PI at Stanford and volunteered since my age, degree of deterioration, etc. fit the study parameters. At age 71 I became Patient #1, the first person in the world with Parkinson’s to undergo the young plasma treatment.

Phase I tests safety, not efficacy. However, the inevitable question on the table is whether or not this might work. Each week I flew back and forth to Stanford, receiving two infusions each trip. I had three extensive two day On and Off medication tests: before starting the infusions, at the end of the eight infusions and 5.5 weeks after the last infusion. My response was remarkable and unexpected. My UPDRS score in both On and Off testing was cut in half from the beginning to the 5.5 post-infusion week mark. Things that disappeared: dystonia, irritable bowel, constipation, gas, nausea, anxiety, weariness, apathy, need to nap. Things that returned: sense of smell, high energy, sleeping through the night, confidence. New things: dyskinesia (to a small extent), tremor (increased slightly). I wondered if the dyskinesia and tremor reflected too much dopamine in my system so, with the agreement of my doctor, I cut back my Sinemet from 4.5 tablets per day to 4.0. Both issues were somewhat, although not completely, resolved. Great!

What about the other people in the trial? There are to be 18 all together with testing ending by the end of 2017 and analysis finished by the end of 2018. In the meantime, I get no more plasma and no more testing to see how I’m doing. I keep records anyway and send them in to Stanford. One of the other women in the trial contacted me before she began the study. She has called me regularly to say how she’s doing and we actually met on my last visit to Palo Alto. Her report: nothing changed. How could that be?

Here’s where I go back to my original observation that there are many kinds of Parkinson’s that will call for various in treatments, and a further observation that treatments will most likely be effective when modalities are combined. The other patient doesn’t exercise and would not be considered fit. I exercise like a maniac. Dr. Alberts has shown that when people cycle as per his protocols, the same areas of the brain that are activated by medicine are activated by cycling. Cycling IS medicine. We know that medicine slows the progression of the disease but doesn’t stop it. Same for cycling. But WHAT IF?? WHAT IF?? medicine, cycling AND young blood infusions put us over the tipping point so that the disease is stopped, or even, as seems to be with my body, is reversed?

My last infusion was Valentine’s Day, 2017. More than two months later, despite some slipping, I’m still doing quite well. I feel I could do even better. The symptoms I got rid of slowly are sneaking back into the matrix. I’m told that Phase I will end in 2018, hopefully followed by Phases II and III and FDA approval. That will take at least 10 years, probably more. I’m 71. Do the math.

What would I like to see? There are over 30 Pedaling for Parkinson’s programs currently operating in the US, primarily at YMCAs, which could provide a prepared, eager resource of clinical trial participants who already take pill medicine and cycle medicine regularly. A new trial could reflect a subset of Parkinson’s patients whose inclusion criteria include medicine and cycling or other exercise that has a proven track record with PD patients. If it were successful, it would be a game changer in the world of Parkinson’s. If it weren’t successful, at least we would have some answers without waiting 10 years.

35 Replies

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  • Remarkable, NanCyclist!

  • So true! And I would go.

  • Absolutely stunning.

    One of the mos interesting posts published here.

    Thank you for giving us so much hope, NanCyclist.

  • medicalxpress.com/news/2017...

    "The time has come to ask what we should be doing differently," Espay says. "Medical science has made a global investment of $23 billion in therapies with the promise to slow down the progression of Parkinson's disease, and the 17 completed phase III clinical trials have yielded little more than disappointment. We need to ask whether the growing number of failed trials might be explained by our single-target and single-disease approach to drug development."

    Espay and his colleagues theorize that Parkinson's is not one disease but rather several diseases when considered from genetic and molecular perspectives. They acknowledge that viewing Parkinson's as a single disorder that predominantly involves dopamine-neuron degeneration has been useful in the development of treatments for symptoms, such as tremor and unstable walking, that touch the vast majority of patients. At the same time, this view has yet to deliver a therapy that is effective in slowing, modifying or curing Parkinson's. One important reason, Espay says, could be that promising molecular therapies have been tested in large clinical trials of people who share the diagnosis of Parkinson's, but not to the specific disease subtype most likely to benefit.

    The researchers advocate a "precision medicine" approach that is rooted in systems biology, an inter-disciplinary study that focuses on the complex interactions of biological systems.

    "Looking at the disease from a systems biology perspective allows us to recognize that our patients can be divided into subtypes based on genetic, biological and molecular abnormalities," Espay says. "As a result, they will respond differently to different therapies."

    Neurologists have long observed the many faces of Parkinson's in their patients. Some progress rapidly in their disease, some slowly. Some develop dementia relatively early, while others do not.

    Read more at: medicalxpress.com/news/2017...

    As you will be pleased to see the scientists have finally realised after 23 billion on research that they need to change their track, but will they is anyone's guess, they also agree its time to start LISTENING to PWP as they are the ones who hold the key to a cure,

    I am also an advocate for cycling and believe it has slowed my progression.I admire you taking part in the trial immensely and hope it is not another dead end.

  • I found it almost spooky reading Dr. Espey's article. How strange that we would come to the same conclusions from such different directions. My ideas are based on thoughtful observation of myself and others and his are conclusions reached from a scientific perspective. I think I would like this man! Thanks for posting this.

  • Nan, you may be having memory problems.

    Please see post #37 (03-24-2017) on the "The Stanford Parkinson's Disease Plasma Study (SPDP)" thread at NT.

    Jeff

  • That's what's really spooky Jeff. I had completely forgotten that I had read that article. I hope this doesn't portend more serious memory problems. I wrote that the last day of my followup testing at Stanford. Thanks for pointing it out.

  • No worries, Nan. Something quite similar happened to me recently.

  • Extremely interesting and thought provoking post.

    Thank you for sharing this with us.

    All the best for your future.

  • Great post.Many thanks :-)

  • Nan.

    Thank you, thank you, thank you. You capture the problem perfectly and lay out a logical solution. Around your last paragraph, I was thinking Where do we go with this? Who calls the shots on how studies are conducted? NIH? FDA? Parkinson's Trust? MJFoxFdtn? How do we turn around the thinking of those controlling the clinical trials?

    How do we get them up to 85RPM on this?

    First year after my diagnosis, I'd look for trials but so many required virgins - PWP who hadn't taken dopiminergic drugs - and i was not one. It was dispiriting. I pretty much gave up on trials and put my attention on exercise, thinking that he brain growth factor benefit might at least make me more receptive to whatever drug/cure/ treatment that might be developed.

    That amounts to a waiting game, but your essay strikes me as a call to action. Any thoughts on where to go from here?

  • I'm interested to hear what others will have to say. In the meantime, the trials are the best the research community has to offer and I think it is important that we all do our best to participate in as many as possible. I think participation insures our credibility.

  • Hi Nan.

    It’s important of course that PWP continue to take part in trials.

    Perhaps I misread the initial post's point. I thought it was that trials could be more productive if they took into account things such as the subject’s level of exercise and what other drugs they were taking. Coming as this did shortly after the piece on Dr. Espay’s call to fine tune trials for particular types of PD, I was simply wondering what we PWP could do to push that approach along.

    Cheers,

    M

  • I recommend you contact everyone you know to express your point of view. You have permission to use my words and you can reference Dr. Espay's article as well. You are the voice of PwPs. We all are.

  • I have no reason to believe there ever will be A cure, as in eradication, globally speaking, of Parkinson's, in any one of today's person's lifetime. I see the disease as genetically and environmentally evolutionary over the very long time. I believe all humans have some form of pre-disposition to PD (as to other 'diseases'). Managing, over time, the multitude of identifiable and changing symptoms experienced by PWP's constitutes our daily challenge, using available and continually developing strategies and tactics based on our limited knowledge. The search for THE 'cure' must nonetheless continue as well as the search for THE 'cause'. Thank you Nan for your quite thoughtful/experiential/personal perspective...continue the search...I will reap its benefits.

  • Dear Nan,

    You are my mentor of cycling enthusiasm.

    You also have a unique talent to record complex ideas in a clear fashion.

    I offer this tidbit as a healthy caveat about cause and effect in PD. In your writing, you mentioned a lady who does not exercise and she also received a lesser response from the plasma infusion. I would suggest that there is a confounding factor as powerful as exercise and that is PAF (Positive Attitude Factor) manifest by hope, faith, persistence, determination, and outlook. Exercise and PAF are positively correlated; one usually does not occur without the other and the two together generate an even more enhanced outcome. How so? The PAF actually improves neuro-biologic activity (better use of residual dopamine, serotonin, norepinephrine confirmed by blinded MRI studies); thus, some of the subjective outcomes measures that you outlined would be predictably better in a study group that has the grit to climb Kilimanjaro.

    Here’s the hard part! Any study of subjective and objective outcomes should (at least theoretically) control for PAF (which is a quality measure that is poorly quantified). If we can’t control for it in studies, we should at least exploit it in our daily lives. You have!

    I have found it helpful to study the paths of others who are fighting or have fought motor impairment. I list Nancyclist as a current star. An ancient star was King David who left clues that he may well have had PD; he left recommendations that remain current for PD. The Medici (Godfathers of the Italian Renaissance) had severe motor impairments but gave us Florence Italy. Hitler had PD and used his motivation to do evil. We can learn from all four.

    What do I know?? I am just a retired and shuffling surgeon 5 years into this trembly journey.

    Tribselyov

    WWW.CRVOYLES.COM

  • I really like the PAF addition to the discussion. I think you're right spot on with that one.

  • Excellent contribution and very helpful Doctor! I also advocate exercising each day! With the release of endorphins, exercise helps with a positive approach to coping and helping with one fighting the sometimes, frustrating symptomology of having a Parkonism type diagnosis.

  • Visiting the European Parkinsons therapy centre in Italy empowered me to take control of PD .PD is living with me ,I'm no longer living with PD.

    I am better than I was 6 years ago when I was living with PD. I could barely ride 25 kms on my bike,only play an hours tennis and having to give up mountain walking, I had extreme fatigue to the point of exhaustion , had to nap every day and depressed with suicidal thoughts.

    Since taking control I can ride 50 km twice a week ,play tennis 2 hrs twice a week and power walk In between.Im still able to ski albeit for 2-3 days not6-7. I am no longer depressed and rarely nap.

    I don't have on /off periods,,I have normal periods and takes a little longer periods

    Life's too short to dwell on the past or think of the future ,I am mindful and live in the moment,I live every day as if my last .That way there's no 'if only '

    Parkinsons is my inconvenience, I definitely have the PAF, I have a wonderful life-which I am thankful for every waking moment.

  • Can you tell us what you've been doing? Thanks

  • Whom are you asking, Parkie 13?

  • I'm asking Bazillion, sorry

  • Accepting PD , that it's living with me not me with it!

    I try to be mindful ,live in the moment,Focus on what I can do ,not what I used to do.

    At the centre they challenged me to push myself far more than I thought I was capable of.

    One day I did 30,000 steps,yes 30.000. That's not expected of anyone but I knew I had to prove to myself I could.

    It makes the 10,000 a day recommendation achievable ,but you have to believe in yourself.

    I have 2 x50 km bike rides a week,play tennis 2 hrstwice a week,try and get a power walk in once a week,ski ,have a quarter acre garden,.

    I have a wonderful group of friends and my wife is 100% supportive,and motivating, we do all these activities together.

    No one can do it for me I know Ihave to put the effort in to reap the rewards,and that is slowing the progression of PD.

  • I thought the study patients were not suppose to all get the treatment, (some get a placebo and others the real thing). So how did your friend know she did not get the placebo?

  • This is phase 1 in which everyone gets the real thing to see if it is safe. Phase II is the blinded trial.

  • thanks

  • I was diagnosed 17 years ago by a by a Doctor that was head of neurology at a very large hospital and university. He told me then exactly what you have said . He said that someday PD would be a collective name for 15 to 20 different diseases, and that exercise was the only thing that so far can help besides medication and that the medication while relieving some symptoms created it own problems.

    There is hope, but now I am just tired and here lies the problem.

    It is the next phase of the disease , I am told it can be delayed and I am trying but how does one exercise when totally exhausted. Sometimes I cant get my leg over the stationary bike and when I do , I still fall asleep. If indeed PAF is real ,it is destroyed by exhaustion, it just drips away with the energy and both are lost and then pain creeps back in to replace them.

    "Autopsy is not the most effective way to identify a disease. "

    IT DOES NOT HURT THOUGH

    I am reading your post again, very interesting, excellence, thank you

  • One day at a time. Sometimes, one hour at a time. Know that others are pulling for you.

  • Exhaustion is a common symptom of PD. If you are taking Azilect, try selegiline instead, and try it anyway if you are not currently taking it. Amantadine is also said to help with exhaustion. That didn't work for me because it aggravated my dry mouth. Bu if you can tolerate it ok it's worth a try.

  • Remarkable, intelligent observations! Thank you for sharing this ma'am! Your efforts to help yourself are laudatory. I agree with you. Actually, an initial diagnosis of Parkinsonism covers a variety of symptoms and diseases, that seem to be all related. I will follow up on some of your suggestions for my own diagnosed PD. I am very familiar with the Cleveland Clinic, having lived in Cleveland for many years. My wife had heart bypass surgery at the Cleveland Clinic, many years ago! It is an excellent medical institution! Good luck to you!

  • Hi Nan,

    Interesting theory and one that certainly has merit. I too believe the ideal combination of meds, supplements, food, exercise, and attitude (aka 'lifestyle') holds the key to relieving our symptoms. Maybe a couple doses of young plasma is all that's missing(?). Despite PD's varied, ever-changing set of symptoms, the one common factor that we share (like cancers share DNA/gene mutation) is the shortage of dopamine producing neurons. And, although there are thus far no reliable biomarkers for confirming a diagnosis of Parkinson's, there does exist the means for confirming a 'parkinsonian' condition.

    Among the "Inclusion Criteria" for the Stanford study for which you qualified were "a diagnosis of clinically probable or established Parkinson's Disease (MDS criteria)", and participants "must be on a stable dose of dopaminergic medication and/or Deep Brain Stimulation (DBS)". In other words, you had to first demonstrate your dopamine shortage via a positive response to l-dopa meds - the "levadopa challenge", or via more rigorous diagnostics like DaTscan/DAT SPECT "to help rule out other diseases that may have similar symptoms, like essential tremor" (individuals diagnosed with essential tremor and those who fail to respond to dopamine therapy would not qualify i.e., individuals like J.Pepper).

    In any case, the generous account of your clinical trial experience is honest, thorough, and MUCH appreciated. As you meticulously detail, however, certain symptoms within that ever-changing set seem to have intensified since your treatment (dyskenesia, tremor), there's been "some slipping", and some symptoms are slowly "sneaking back into the matrix". Like most who find themselves here on HU's PD forum, I'm really hoping you continue to get stronger, that your symptoms continue to improve, and (of course) that you continue to post your progress. I also hope you will continue to exercise some patience before declaring your disease "reversed" (we already have one of those).

    pdf.org/en/science_news/rel...

    ncbi.nlm.nih.gov/pmc/articl...

  • So many people have responded positively to my post on Parsing Parkinson's. I honestly have no recollection of having read the article by Dr. Alberto Espay "Researchers help map future of precision medicine in Parkinson's disease..." that outlines my thoughts in a similar fashion. Although I recognize that my ideas take a long time to take shape, I was astonished at how closely they parallel Dr. Espay's analysis. The fact that I referenced his article in a post on NeuroTalk and didn't realize I had even read it ...

    Not to worry about me claiming my PD is reversed. There is too much evidence that it is not!

  • Sign me up! I was diagnosed with PD in April of 2011. Prior to receiving that devastating news, I had always been quite active and kept myself physically fit. I had ridden across the State of Iowa 12 times, 3 times on a tandem, with my wife. We had also taken several week-long tandem bike trips in Minnesota, Michigan and Wisconsin. I loved to all sorts of other sporting activity, but then, between 2013 and 2017, I had to undergo 4 lumbar fusion surgeries. Thanks to the unhappy combination of degenerative disc disease, Parkinson's Disease and spending way too much time on an operating table, I have lost a significant amount of muscle mass and tone and my stamina is shot. Nonetheless, with proper rehab (starting next week) and plenty of time on my Star Trac Spinner XRT (simple, barebones, but providing smooth 80-100 RPM spinning) AND inspiration provided by you, my dear lady, I am confident that I will bounce back.

  • I think I am very lucky to have What we call PD lite, kind of like Miller lite, only Parkinson's. I don't have any of the lumbar issues you have or cancer or any of the other things that so many people suffer with. I've had the plasma infusions. I take medicine for PD, exercise like a maniac and my symptoms are pretty much under control. It warms my heart to think that I'm an inspiration for you. I'm sure you're an inspiration for many others. We all have a positive role to play.

  • You may have lost a lot of muscle mass and stamina but with yourPAF past sporting history and a wife who rides tandem you have every reason to bounce back.Give it hell and show PD who's in charge. I know you can do it.Good luck.

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