Category Archives: Clinical trial

Complementary and Alternative Medicine (CAM) and Over-the-Counter Therapies in Parkinson’s

With Parkinson’s, exercise is better than taking a bottle of pills. If you don’t do anything you’ll just stagnate.” Brian Lambert

“With Parkinson’s you have two choices: You can let it control you, or you can control it. And I’ve chosen to control it.” US Senator Isakson

Introduction: Having one of the numerous neurodegenerative disorders can be disheartening, difficult and life-threatening/ending; however, Parkinson’s remains in the forefront of treatment schemes and therapeutic options.  We may have a slowly evolving disorder, yet I remain firmly entrenched both in striking back to try-to-slow its progression and in remaining hopeful that new advances are on the horizon to throttle-back its progression.  Recently, several people have asked for an update on my strategy for treating Parkinson’s.  My plan consists of (i) traditional Parkinson’s medication,  (ii) supplemented by a complementary and alternative medicine (CAM) approach, and (iii) fueled by exercise. My philosophy is simple because I truly believe there are steps I can follow to remain as healthy as possible, which include having a positive mindset to support this effort, and to accept the axiom of the harder I try the better I’ll be.

“Life is to be lived even if we are not healthy.” David Blatt

Complementary and Alternative Medicine (CAM):The National Institutes of Health defines CAM as follows: “Complementary and alternative medicine (CAM) is the term for medical products and practices that are not part of standard medical care. ‘Complementary medicine’ refers to treatments that are used with standard treatment. ‘Alternative medicine’ refers to treatments that are used instead of standard treatment.”  Here is a nice overview of CAM (click here). The National Center for CAM (click here for NCCAM) gives five categories to broadly describe CAM (see below, and followed by some representative components for each of the 5 categories):

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(1) Alternative medical systems include treatment by traditional Chinese medicine, Ayurveda and naturopathic medicine;
(2) Mind-body interventions like mindfulness meditation;
(3) Biologically-based therapies include over-the-counter natural products and herbal therapies;
(4) Manipulative and body-based methods describe chiropractic and massage therapies;
(5) Energy therapies include techniques such as Reiki and therapeutic touch.

“My way of dealing with Parkinson’s is to keep myself busy and ensure my mind is always occupied.” David Riley

CAM and Parkinson’s: Published CAM clinical trial studies have yielded only a sliver of positive response to slowing the progression of Parkinson’s, several were halted due to no change compared to the placebo-control group. Regardless of these ‘failed’ studies, many have embraced a CAM-based approach to managing their disorder, including me. Please remember that I’m not a clinician, and I’m not trying to convince you to adopt my strategy.  I am a biochemist trained in Hematology but I do read and ponder a lot, especially about Parkinson’s.  We know a lot about Parkinson’s and we’re learning a lot about the molecular details to how it promotes the disease.  There is not a cure although we have a growing array of drugs for therapeutic intervention.  Without a  cure, we look at the causes of Parkinson’s (see schematic below), we consider various CAM options, and we go from there (see schematic below). If you venture into adding to your portfolio of therapy, it is imperative you consult with your Neurologist/family medicine physician beforehand.  Your combined new knowledge with their experience can team-up to make an informed decision about your herb, over-the-counter compound use and its potential benefit/risk ratio.

17.12.31.PD_Cause.CAM“I discovered that I was part of a Parkinson’s community with similar experiences and similar questions that I’d been dealing with alone.”Michael J. Fox

A strategy for treating Parkinson’s: The treatment plan I follow uses traditional medical therapy, CAM (several mind-body/manual practices and numerous natural products) and the glue that ties it all together is exercise.  Presented here is an overview of my medical therapy and CAM natural products. I only list the exercises I am using, not describe or defend them.  Due to my own personal preference for the length of a blog post, I will return to them later this year and include an update of the mind-body/manual practices that I’m currently using. Please note that these views and opinions expressed here are my own. Content presented here is not meant as medical advice. Definitely consult with your physician before taking any type of supplements.   The schematic below gives a ‘big-picture’ view of my treatment strategy.

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To some, my treatment plan may seem relatively conservative. It has been developed through conversations with my Neurologist and Internist.  This was followed by studying the medical literature on what has worked in Parkinson’s treatment, the list of compounds to consider was defined/refined (actually, my choice of OTC compounds has been trimmed from several years ago).  My CAM drug/vitamin/natural products strategy for treating Parkinson’s goes as follows: a) compounds (reportedly) able to penetrate the blood brain barrier; b) compounds (possibly) able to slow progression of the disorder; c) compounds that either are anti-oxidative or are anti-inflammatory; d) compounds that don’t adversely alter existing dopamine synthesis/activity; e) compounds that support overall body well-being; and f) compounds that support specific brain/nervous system health/nutrition. [Please consult with your physician before taking any type of supplements.] The Table below presents a detailed overview of my strategy for treating Parkinson’s.

18.01.01.DailyTherapy4Note of caution: Most herbs and supplements have not been rigorously studied as safe and effective treatments for PD. The U.S. Food and Drug Administration (FDA) does not strictly regulate herbs and supplements; therefore, there is no guarantee of safety, strength or purity of supplements.

REPLACING DOPAMINE:
On a daily basis, I use a combination of Carbidopa/Levodopa (25 mg/100 mg tablet x 4 daily, every 5 h on an empty stomach if possible, typically 6AM, 11AM, 4PM, 9PM) and a dopamine agonist Requip XL [Ropinirole 6 mg total (3 x 2 mg tablets) x 3 daily, every 6 h, typically 6AM, noon, 6PM).  This treatment strategy and amount combining Carbidopa/Levodopa and Ropinirole has been in place for the past 18 months (NOTE: I stopped using the additional dopamine agonist Neupro transdermal patch Rotigotine). For an overview on Carbidopa/Levodopa, I highly recommend the following 2 papers:
[1.] Ahlskog JE. Cheaper, Simpler, and Better: Tips for Treating Seniors With Parkinson Disease. Mayo Clinic Proceedings. 2011;86(12):1211-6. doi: https://doi.org/10.4065/mcp.2011.0443.
[2.] 1. Espay AJ, Lang AE. Common Myths in the Use of Levodopa in Parkinson Disease: When Clinical Trials Misinform Clinical Practice. JAMA Neurol. 2017. doi: 10.1001/jamaneurol.2017.0348. PubMed PMID: 28459962.

ISRADIPINE:
An FDA-approved calcium-channel blocker (CCB) named Isradipine penetrates the blood brain barrier to block calcium channels and potentially preserve dopamine-making cells. Isradipine may slow the progression of Parkinson’s. The primary use of Isradipine is in hypertension; thus, to treat my pre-hypertension I switched from the diuretic Hydrochlorothiazide to the CCB Isradipine.  A CCB is a more potent drug than a diuretic; importantly, my blood pressure is quite normal now and maybe I’m slowing the progression of my Parkinson’s. Please see this blog post for a review of Isradipine (click here). [Please consult with your physician before taking any type of new medication.

ANTIOXIDANTS/VITAMINS/GENERAL HEALTH:
N-Acetyl-Cysteine (NAC; 600 mg x 3 daily) is a precursor to glutathione, a powerful anti-oxidant. In several studies, NAC has been shown to be neuroprotective in Parkinson’s (click here).  I have recently posted an overview of NAC (click here). Furthermore, the ‘Science of Parkinson’s disease’ has presented their usual outstanding quality in a blog post on NAC in PD (click here);
trans-Resveratrol (200 mg daily) is an antioxidant that crosses the blood-brain barrier, which could reduce both free-radical damage and inflammation in Parkinson’s. If you decide to purchase this compound, the biologically-active form is trans-Resveratrol. The ‘Science of Parkinson’s disease’ has an excellent blog post on Resveratrol in PD (click here);
Grape Seed (100 mg polyphenols, daily) is an antioxidant that crosses the blood-brain barrier, which could reduce both free-radical damage and inflammation in Parkinson’s;
Milk Thistle (Silybum Marianum, 300 mg daily) and its active substance Silymarin protects the liver.  Dr. Jay Lombard in his book, The Brain Wellness Plan, recommends people with PD who take anti-Parkinson’s drugs (metabolized through the liver) to add 300 mg of Silymarin (standardized milk thistle extract) to their daily medication regime.
Melatonin (3 mg 1 hr before sleep) Melatonin is a hormone that promotes sustained sleep. Melatonin is also thought to be neuroprotective (click here);
Probiotic Complex with Acidophilus is a source of ‘friendly’ bacteria to contribute to a healthy GI tract.
Vitamin (daily multiple)
A high-potency multivitamin with minerals to meet requirements of essential nutrients, see label for content [I only take 1 serving instead  of the suggested 2 gummies due to my concern about taking a large amount of Vitamin B6 as described in a recent blog (click here)]:
IMG_2059 copyVitamin D3 (5000 IU 3 times/week) is important for building strong bones. Now we also know that vitamin D3 is almost like ‘brain candy’ because it stimulates hundreds of brain genes, some of which are anti-inflammatory and some support nerve health (click here). Supplementation with vitamin D3 (1200 IU/day) for a year slowed the progression of a certain type of Parkinson’s (click here). Furthermore, augmentation with vitamin D3 was recently shown to slow cognitive issues in Parkinson’s (click here).

NO LONGER TAKE Coenzyme Q10 (CoQ10), Creatine and Vitamin E because they did not delay the progression of Parkinson’s or they were harmful.
NO LONGER TAKE a high potency Vitamin B Complex (see label below) due to my concern that a large excess vitamin B6 could be detrimental to Carbidopa/Levodopa (click here for blog post):
Screen Shot 2018-01-02 at 11.39.56 PM
List of several recent PubMed peer-reviewed CAM reviews (includes a more comprehensive overview of all areas of CAM in treating Parkinson’s):
Bega D, Zadikoff C. Complementary & alternative management of Parkinson’s disease: an evidence-based review of eastern influenced practices. J Mov Disord. 2014;7(2):57-66. doi: 10.14802/jmd.14009. PubMed PMID: 25360229; PMCID: PMC4213533.

Bega D, Gonzalez-Latapi P, Zadikoff C, Simuni T. A Review of the Clinical Evidence for Complementary and Alternative Therapies in Parkinson’s Disease. Current Treatment Options in Neurology. 2014;16(10):314. doi: 10.1007/s11940-014-0314-5.

Ghaffari BD, Kluger B. Mechanisms for alternative treatments in Parkinson’s disease: acupuncture, tai chi, and other treatments. Curr Neurol Neurosci Rep. 2014;14(6):451. doi: 10.1007/s11910-014-0451-y. PubMed PMID: 24760476.

Kim HJ, Jeon B, Chung SJ. Professional ethics in complementary and alternative medicines in management of Parkinson’s disease. J Parkinsons Dis. 2016;6(4):675-83. doi: 10.3233/JPD-160890. PubMed PMID: 27589539; PMCID: PMC5088405.

Kim TH, Cho KH, Jung WS, Lee MS. Herbal medicines for Parkinson’s disease: a systematic review of randomized controlled trials. PLoS One. 2012;7(5):e35695. doi: 10.1371/journal.pone.0035695. PubMed PMID: 22615738; PMCID: PMC3352906.

Wang Y, Xie CL, Wang WW, Lu L, Fu DL, Wang XT, Zheng GQ. Epidemiology of complementary and alternative medicine use in patients with Parkinson’s disease. J Clin Neurosci. 2013;20(8):1062-7. doi: 10.1016/j.jocn.2012.10.022. PubMed PMID: 23815871. 

Today we take control over our Parkinson’s:
Please stay focused on dealing with your disorder.
Please learn as much as you can about Parkinson’s.
Please work with your neurologist to devise your own treatment strategy.
Please stretch and exercise on a daily basis, it will make a difference.
Please be involved in your own disorder; it matters that you are proactive for you.
Please stay positive and focused as you deal with this slowly evolving disease.
Please stay hopeful you can mount a challenge to slow the progression.
Please remain persistent; every morning your battle renews and you must be prepared.

 

In the midst of winter, I found there was, within me, an invincible summer.  And that makes me happy. For it says that no matter how hard the world pushes against me, within me, there’s something stronger – something better, pushing right back.” Albert Camus

Cover photo credit: news.nowmedia.co.za/medialibrary/Article/109153/Wine-grape-crop-6-7-down-in-2016-800×400.jpg

 

Parkinson’s Disease Research: A Commentary from the Stands and the Playing Field

“You can have a very bad end with Parkinson’s, but on the other hand, you can be like me, because I’m lucky. I’m not having a bad end.” Margo MacDonald

“My age makes me think how valuable life is. How bad is something like Parkinson’s in relation to not having life at all?” Michael J. Fox

Introduction: Last month, together with Dr. Simon Stott and his team of scientists (The Science of Parkinson’s Disease), we co-published a historical timeline of Parkinson’s disease beginning with the description of the ‘shaking palsy’ from James Parkinson in 1817. My post entitled “Milestones in Parkinson’s Disease Research and Discovery” can be read here (click this link). The Science of Parkinson’s Disease post entitled “Milestones in Parkinson’s Disease Research and Discovery” can be read here (click this link).

We spent a lot of time compiling and describing what we felt were some of the most substantial findings during the past 200 years regarding Parkinson’s disease.  I learned a lot; truly amazing what has been accomplished in our understanding of  such a complex and unique disorder.  Simon posted a follow-up note entitled “Editorial: Putting 200 years into context” (click this link). I have decided to also post a commentary from the standpoint of (i) being someone with Parkinson’s and (ii) being a research scientist.

“Every strike brings me closer to the next home run.” Babe Ruth

Baseball: I want to use the analogy of a baseball game to help organize my commentary. Baseball fans sit in the stands and have fun watching the game, thinking about the strategy behind the game, eating/drinking, and sharing the experience with family/friends/colleagues.   Most baseball players begin playing early in life and the ultimate achievement would be to reach the major leagues. And this would usually have taken many years of advancing through different levels of experience on the part of the ballplayer. How does how this analogy work for me in this blog? Stands: I am a person-with-Parkinson’s watching the progress to treat and/or cure this disorder. Playing field: I am a research scientist in a medical school (click here to view my training/credentials).

“Never allow the fear of striking out keep you from playing the game!”  Babe Ruth

Observation from the stands:
I am a spectator like everyone else with Parkinson’s. I read much of the literature available online.  Like you, I think about my disorder; I think about how it’s affecting me every day of my life. Yes, I want a cure for this disease.  Yes, I’m rather impatient too.  I understand the angst and anxiety out there with many of the people with Parkinson’s. In reality, I would not be writing this blog if I didn’t have Parkinson’s. Therefore, I truly sense your frustration that you feel in the presence of Parkinson’s, I do understand.  Given below are examples of various organizations and ads and billboards in support of finding a cure for Parkinson’s.  Some even suggest that a cure must come soon.   However, the rest of my post is going to be dedicated to trying to explain why it’s taking so long; why I am optimistic and positive a cure and better treatment options are going to happen.  And it is partly based on the fact that there really are some amazing people working to cure Parkinson’s and to advance our understanding of this disorder.

“When you come to a fork in the road take it.” Yogi Berra

Observations from the playing field (NIH, war on cancer, research lab, and advancing to a cure for Parkinson’s):

National Institutes of Health (NIH) and biomedical research in the USA: Part of what you have to understand, in the United States at least, is that a large portion of biomedical research is funded by the NIH (and other federally-dependent organizations), which receives a budget from Congress (and the taxpayers). What does it mean for someone with Parkinson’s compared to someone with cancer or diabetes? The amount of federal funds committed to the many diseases studied by NIH-funded-researchers are partly divvied up by the number of people affected. I have prepared a table from the NIH giving the amount of money over the past few years for the top four neurodegenerative disorders, Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), and Huntington’s Disease, respectively [taken from “Estimates of Funding for Various Research, Condition, and Disease Categories” (click here)]. And this is compared to cancer and coronary arterial disease and a few other major diseases. Without going into the private organizations that fund research, a large amount of money comes from the NIH. Unfortunately, from 2003-2015, the NIH lost >20% of its budget for funding research (due to budget cuts, sequestration, and inflationary losses; click here to read further).   Therefore,  it is not an overstatement to say getting  funded today by the NIH is fiercely competitive.  From 1986 to 2015, my lab group was supported by several NIH grants and fellowships  (and we also received funding from the American Heart Association and Komen for the Cure).

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“In theory, there is no difference between theory and practice. But in practice, there is.” Yogi Berra

War against cancer: In 1971, Pres. Richard Nixon declared war against cancer and Congress passed the National Cancer Act.  This created a new national mandate “to support research and application of the results of research to reduce the incident, morbidity, and mortality from cancer.” Today, cancer is still the second leading cause of death in the USA; however, we’ve come such a long way to improving this statistic from when the Cancer Act was initiated.

Scientifically, in the 1970’s, we were just learning about oncogenes and the whole field of molecular biology was really in its infancy. We had not even started sequencing the human genome, or even of any organism.  We discovered genes that could either promote or suppress cellular growth.   We began to delineate the whole system of cell signaling and communications with both normal and malignant cells. We now know there are certain risk factors that allow us to identify people that may have increased risk for certain cancers. Importantly,  we came to realize that not all cancers were alike,  and it offered the notion to design treatment strategies for each individual cancer.  For example,  we now have very high cure rates for childhood acute leukemia and Hodgkin’s lymphoma and we have significantly improved survival statistics for women with breast cancer. Many might say this was a boondoggle and that we wasted billions of dollars  funding basic biomedical research on cancer; however, basic  biomedical research is expensive and translating that into clinical applications is even more expensive.  [ For a  very nice short review on cancer research please see the following article, it may be freely accessible by now: DeVita Jr, Vincent T., and Steven A. Rosenberg. “Two hundred years of cancer research.” New England Journal of Medicine 366.23 (2012): 2207-2214.]

“One of the beautiful things about baseball is that every once in a while you come into a situation where you want to, and where you have to, reach down and prove something.” Nolan Ryan

The biomedical research laboratory environment:  A typical laboratory group setting is depicted in the drawing below. The research lab usually consists of the lead scientist who has the idea to study a research topic, getting grants funded and in recruiting a lab group to fulfill the goals of the project.  Depending on the philosophy of the project leader the lab may resemble very much like the schematic below or may be altered to have primarily technicians or senior postdoctoral fellows working in the lab  (as two alternative formats). A big part of academic research laboratories is education and training the students and postdocs to go on to advance their own careers; then you replace the people that have left and you continue your own research.  Since forming my own lab group in 1986, I have helped train over 100 scientists in the research laboratory: 17 graduate students, 12 postdoctoral fellows, 17 medical students, and 64 undergraduates. The lab has been as large as 10 people and a small as it is currently is now with two people. People come to your lab group because they like what you’re doing scientifically and this is where they want to belong for their own further training and advancement.  This description is for an academic research  laboratory; and  I should also emphasize that many people get trained in federal government-supported organizations, private Pharma and other types of research environments that may differ in their laboratory structure and organizational format.

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“Hitting is 50% above the shoulders.” Ted Williams

 In search of the cure for Parkinson’s:    First, I understand the situation you’re in with Parkinson’s because I’m living through the same situation.   But when people find out I’m a research scientist they always wonder why aren’t we doing more to find a cure, and I  hear the sighs of frustration and I see the anxiety in their faces. Second, the previous three sections are not meant to be an excuse for why there is still no cure for Parkinson’s. It is presented in the reality of what biomedical research scientists must undergo to study a topic.  Third, the experiments that take place in basic biomedical research laboratory may happen over weeks to months if successful. Taking that laboratory data to the clinic and further takes months and years to succeed if at all.   The section on cancer reminds me a lot of where we are going with Parkinson’s and trying to advance new paradigms in the treatment and curative strategies.  Professionally, I have even decided  to pursue research funding in the area of Parkinson’s disease.   Why not spend the rest of my academic career studying my own disease; in the least I can help educate others about this disorder. Furthermore, I can assure you from my reading and meeting people over the last couple of years, there are many hundreds of scientists and clinicians throughout this world studying Parkinson’s and trying to advance our understanding and derive a cure.  I see their devotion, I see their commitment to helping cure our disorder.

The science behind Parkinson’s is quite complicated. These complications suggest that Parkinson’s may be more of a syndrome rather than a disease. Instead of a one-size-fits-all like a disease would be classified; Parkinson’s as a syndrome would be a group of symptoms which consistently occur together.  What this might imply is that some treatment strategy might work remarkably well on some patients but have no effect on others. However, without a detailed understanding and advancement of what Parkinson’s really is we will never reach the stage where we can cure this disorder.

bright-future-ahead-1024x772
In a recent blog from the Science of Parkinson’s disease, Simon nicely summarized all the current research in 2017 in Parkinson’s disease (click here to read this post). To briefly summarize what he said is that there are multiple big Pharma collaborations occurring to study Parkinson’s.  There are more than 20 clinical trials currently being done in various stages of completion to prevent disease progression but also to try to cure the disorder.  From a search of the literature, there are literally hundreds of research projects going on that promise to advance our understanding of this disorder. With the last point, it still will take time to happen. Finally, I am a realist but I’m also optimistic and positive that we’re making incredible movement toward much better therapies, which will eventually lead to curative options for Parkinson’s.

And a final analogy to baseball and Parkinson’s, as Tommy Lasorda said “There are three types of baseball players: those who make it happen, those who watch it happen, and those who wonder what happens.”  I really want to be one of those scientists that help make it happen (or at least to help advance our understanding of the disorder).

“You can’t expect life to play fair with your heart or your brain or your health. That’s not the nature of the game we call life. You have to recognize the nature of the game and know that you can do your best to make the right choices, but life if going to do whatever the hell it pleases to you anyway. All you can control is how you react to whatever life throws at you. You can shut down or you can soar.” Holly Nicole Hoxter

Cover photo credit: PNC Park photo: i.imgur.com/32RWncK

Sign post scienceofparkinsons.com/

“Go the Distance” With MAO-B Inhibitors: Potential Long-term Benefits in Parkinson’s

“Life is 10 percent what you make it, and 90 percent how you take it.” Irving Berlin

“My attitude is that if you push me towards something that you think is a weakness, then I will turn that perceived weakness into a strength.” Michael Jordan

Précis:  (1) A brief review of the major classes of therapeutic compounds for treating Parkinson’s. (2) Defining clinical trials.  (3) Hauser et al.(Journal of Parkinson’s Disease vol. 7, no. 1, pp. 117-127, 2017) report that Parkinson’s patients who received an MAO-B inhibitor for a long period of time had statistically significant slower decline in their symptoms compared to patients not on an MAO-B inhibitor (click here to see paper). (4) Addendum: “New Kid In Town”, The FDA approves another MAO-B inhibitor named Xadago (safinamide). 

Pharmacological treatment of Parkinson’s [Please note that these views and opinions expressed here are my own. Content presented here is not meant as medical advice. Definitely consult with your physician before taking any type of drug.]: The management of Parkinson’s is broadly divided up into motor and non-motor therapy.  A brief description of the therapy for motor dysfunction will be presented here.  Please see the drawing below for an overview.   Within the framework of treating someone with Parkinson’s you must consider managing their symptoms with the hope that some compound might possess either  neuroprotective or neurorestorative actions. To date, we do not have a cure for Parkinson’s but the study described below suggests an existing compound may be neuroprotective when used for a long  time.

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“Things turn out best for the people who make the best of the way things turn out.” John Wooden

Medical management of the motor-related symptoms of Parkinson’s:

Levodopa, together with carbidopa, is the ‘gold standard’ of treatment of motor signs and symptoms. Carbidopa is  a peripheral decarboxylase inhibitor (PDI), which provides for an increased uptake of levodopa in the central nervous system. As shown above, levodopa (denoted as L-DOPA) is converted to dopamine by the dopaminergic neurons. Levodopa is still the most effective drug for managing Parkinson’s motor signs and symptoms. Over time, levodopa use is associated with issues of “wearing-off” (motor fluctuation) and dyskinesia.  For further information about levodopa and dopamine, please see this previously posted topic (click here).

Catechol-O-methyl transferase (COMT) inhibitors prolong the half-life of levodopa by blocking its metabolism. COMT inhibitors are used primarily to help with the problem of the ‘wearing-off’ phenomenon associated with levodopa.

Dopamine agonists are ‘mimics’ of dopamine that pass through the blood brain barrier to interact with target dopamine receptors. Dopamine agonists provide symptomatic benefit and delay the development of dyskinesia compared to levodopa.  Dopamine agonists are not without their own side-effects, which can occur in some patients, and include sudden-onset sleep, hallucinations, edema, and impulse  behavior disorders.  For more information about dopamine agonists,  please see this previously posted (click here).

Finally, monoamine oxidase (MAO)-B is an enzyme that destroys dopamine; thus, MAO-B inhibitors help prevent the destruction of dopamine in the brain. MAO-B inhibitors have some ability to reduce the symptoms of Parkinson’s. The most common severe side effects of MAO-B inhibitors include constipation, nausea, lightheadedness, confusion, and hallucinations.  There may also be contraindications between MAO-B inhibitors with other prescription medications,  vitamins, and certain foods/drinks (e.g., aged cheese and wine). Definitely talk to your doctor and pharmacist about potential drug interactions if you are considering an MAO-B inhibitor in your therapeutic regimen.

“You should just do the right thing.” Dean Smith

What are clinical trials? The simple description is that a clinical trial determines if a new test or treatment works and is safe. The National Institutes of Health (NIH) defines a clinical trial (paraphrased here) as a research study where human subjects are prospectively assigned1 to one or more interventions2 (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.[1The term “prospectively assigned” refers to a predefined process (e.g., randomization) in an approved protocol that stipulates the assignment of research subjects (individually or in clusters) to one or more arms (e.g., intervention, placebo, or other control) of a clinical trial.2An intervention is defined as a manipulation of the subject or subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints.  3Health-related biomedical or behavioral outcome is defined as the prespecified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life.]  For the complete NIH definition, please click here.

As described by ‘ClinicalTrials.gov’, clinical trials are performed in phases; each phase attempts to answer a separate research question. Phase I: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. Phase II: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.Phase III:  The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely. Phase IV: Studies are done after the drug or treatment has been marketed to gather information on the drug’s effect in various populations and any side effects associated with long-term use. A more complete description is included here (click here).

What is important to remember is that clinical trials are experiments with unknown outcomes that must follow a rigorous approach to safely evaluate and possibly validate potential treatments.

“Nothing has ever been accomplished in any walk of life without enthusiasm, without motivation, and without perseverance.” Jim Valvano

NET-PD-LS1 clinical trial went bust on creatine use in treating Parkinson’s: The NET-PD-LS1 clinical trial went from March 2007 until July 2013. NET-PD-LS1 was a multicenter, double blind, placebo-controlled trial of 1741 people with early Parkinson’s. The goal of NET-PD-LS1 was to determine if creatine could slow long-term clinical progression of Parkinson’s (to learn more about this clinical trial go here or go here) . NET-PD-LS1 was one of the largest and longest clinical trials  on Parkinson’s . This clinical trial was stopped after determining there was no benefit to using creatine to treat Parkinson’s.

“It’s what you learn after you know it all that counts.” John Wooden

NET-PD-LS1 clinical trial gets a ‘gold star’ for MAO-B inhibitors in treating Parkinson’s: NET-PD-LS1 was  a thorough and well organized clinical trial.  New results have been published in a secondary analysis of the clinical trial to determine if MAO-B inhibitors for an extended time affected the symptoms of Parkinson’s. Almost half (784) of the patients in NET-PD-LS1 took an MAO-B inhibitor. The MAO-B inhibitors used in NET-PD-LS1 were Rasagiline (Brand name Azilect) and Selegiline (Brand names Eldepryl, Zelapar, or EMSAM).  More than 1600 of the patient’s completed both baseline and one year evaluation/assessment measuring changes in their symptoms (this was done using a combination of five different measurement scales/systems).  Their results were exciting; the patients that were taking an MAO-B inhibitor for a longer time (1 year) had a slower clinical decline (~20% benefit in the magnitude of the decline compared to the patients not taking an MAO-B inhibitor).  These results indicate that MAO-B inhibitors  somehow are able to slow the progression of the symptoms of Parkinson’s.

“Always look at what you have left. Never look at what you have lost.” Robert H. Schuller

Does this prove that MAO-B inhibitors are neuroprotective in Parkinson’s?   The hopeful person inside of me  wants this answer to be yes; however, the scientist that also resides inside of me says no not quite yet.  The goal of neuroprotection is to slow or block or reverse progression of Parkinson’s; and by measuring changes in dopamine-producing neurons.  Early basic science results with MAO-B inhibitors found some neuroprotection in model systems. This new publication reignites the storyline that MAO-B inhibitors are potentially neuroprotective.

“Efforts and courage are not enough without purpose and direction.” John F. Kennedy

A personal reflection about the strategy for treatment of Parkinson’s: MAO-B inhibitors have never been part of my strategy for treating my disorder. I have been using a traditional drug therapy  protocol [Sinemet and Ropinirole] (click here),  supplemented by a  relatively comprehensive CAM approach (click here), bolstered hopefully by a neuroprotective (experimental) agent [Isradipine] (click here), and fortified with as much exercise in my day that my life can handle (click here).  However, there is a constant and dynamic flux/flow of ideas regarding treatment options for Parkinson’s. Thus,  my strategy for treating my disorder needs to be fluid and not fixed in stone. Over the next few weeks, I will be reading more about MAO-B inhibitors, having some serious conversations with my Neurologist and Internist,  with my care partner assessing the risk and benefits of taking an MAO-B inhibitor, and coming up with a consensus team opinion about whether or not I should start taking an MAO-B inhibitor.

Addendum- FDA Approves Xadago for Parkinson’s Disease:
As the Eagles sing in New Kid In Town, “There’s talk on the street; it sounds so familiar / Great expectations, everybody’s watching you”. The first new drug in a decade to treat Parkinson’s is an MAO-B inhibitor named Xadago (Safinamide).  This drug has an interesting past with the FDA before getting approved this week. Is it different? Xadago is for patients using levodopa/carbidopa that are experiencing troublesome “off episodes”, where their symptoms return despite taking their medication. Thus, Xadago is being marketed as an add-on therapy, which is different than existing MAO-B inhibitors because they can be used as stand alone monotherapy. In two separate clinical trials for safety and efficacy of Xadago, compared to patients taking placebo, those taking Xadago showed more “on” time and less “off” time. Interestingly, this is exactly what you’d expect for an MAO-B inhibitor  (sustaining dopamine, see drawing above).  The most common adverse side-effects reported were uncontrolled involuntary movement (side-note: isn’t this what we’re trying to prevent in the first place?), falls, nausea, and insomnia. Clearly, taking Xadago with another MAO-B inhibitor would not be good. Xadago joins a list of other MAO-B inhibitors that are FDA approved for Parkinson’s including Selegiline (Eldepryl, Zelapar, EMSAM) and Rasagiline (Azilect). Whether the efficacy of Xadago is different or improved from existing MAO-B inhibitors remains to be shown; however, having another MAO-B inhibitor may allow Parkinson’s patients the possibility to use the one with the least adverse reactions.  Clearly, close consultation with your Neurologist will be very important before adding any MAO-B inhibitor to your daily arsenal of drugs.  The good news is now you’ve got another option to join the stable of possible MAO-B inhibitors to be used with levodopa/carbidopa.

For the background/rationale behind using “Go the distance” in the title, watch this video clip: Field of Dreams (3/9) Movie CLIP – Go the Distance (1989) HD by Movieclips  (click here to watch Go the Distance).

“Only the mediocre are always at their best. If your standards are low, it is easy to meet those standards every single day, every single year. But if your standard is to be the best, there will be days when you fall short of that goal. It is okay to not win every game. The only problem would be if you allow a loss or a failure to change your standards. Keep your standards intact, keep the bar set high, and continue to try your very best every day to meet those standards. If you do that, you can always be proud of the work that you do.” Mike Krzyzewski

Cover photo image: https://img1.10bestmedia.com/Images/Photos/304499/Pier-orange-sky-compressed_54_990x660.jpg

Dopamine neurons for the drawing wermodified from http://www.utsa.edu/today/images/graphics/dopamine.jpg

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