Last Friday, my wife and I attended the "Grand Challenges in Parkinson's" Patient Track Symposium in Grand Rapids, MI. This 'patients based' seminar was sponsored by the Michigan Parkinson's Foundation (an organization whom I whole-heartily support) and was held in conjunction with the more research-based "Grand Challenges in Parkinson's Disease" symposium. This was a very good seminar, so I thought I would present to you a kind of 'condensed' version of some of the information presented there, from my point of view. Even condensed, it's still a pretty long blog entry, but I wanted to highlight the important items discussed. So here goes!
Updates in Parkinson's Disease Research
This was my favorite presentation, as it discussed some of the updates in current PD research. Plus, the presenter, Patrik Brudin, is working right here at the Van Andel Research Institute!
But before I go into what he talked about, I should give you a few '"layman's terms" of some of the words used in his presentation:
Gene - Those 'building blocks' that make up your DNA and are composed of codes for proteins. They basically tell each cell in your body how to function.
Genetic Mutation - An alteration of a person's DNA that makes a gene different than what it should be in most people.
Inflammation - Your immune system's first reaction to an infection or irritation, like when you have a cut on your finger that gets red.
Alpha Synuclein - The protein that is believed to be involved with 'clumping up' in the brains of Parkinson's patients.
Energy Deficiency - A cell's energy production; in this case, causing the cell to produce inadequate energy.
Free Radicals - The 'extra' molecule thrown off when a cell makes energy. This molecule is implicated in damaging a cell's structure (stress).
Anti-Oxidant - Something that 'absorbs' free radicals so that they can't damage a cell.
Stem Cells - Basic, primitive cells that can be changed into any other type of cell.
Environment 'Insult' - Things in the environment that may cause stress on a cell, such as pesticides.
So... In a nutshell, his presentation revolved around five key points:
What are the changes in the nervous system that underlie PD?
This involved a lot of information on what PD is and how it starts, so I've tried to condense it down to one item. Basically, he stated there are four key cell changes that probably play a role in PD:
Protein Clumping (i.e. Alpha Synuclein)
Energy Deficiency (i.e. A cell's energy production)
Free Radical Stress (i.e. Oxidation)
It is theorized that some or all of these items are involved in PD. He also noted that these may not occur in the Parkinson's brain in any specific order; i.e. they may not occur in the exact order shown above.
Why is it important to know these things? If we could target any or all of these cell changes, we have a chance to either slow or stop Parkinson's.
Can we predict the disease and identify things that trigger it?
In order to predict the disease and identify what may trigger it, we have to understand a little bit about genetics and DNA. Turns out only 5-10% of people have an inherited form of the disease where the genetic mutation can be identified; the remainder probably have some genetic predisposition (or increased chance) for PD, when combined with an environment 'insult' (like pesticides) and normal aging.
He then gave us a very 'oversimplified' discussion of genetics (which was great since we were not 'eggheads' in any way, shape or form!) The thing that impressed me is that, of all your DNA, only about 2% are 'genes' (approximately 19,000 to 20,000 total) - and of those genes only 10-15 really 'cause' PD (i.e. gives the person a 10-100% risk of disease). The rest of your DNA is what they call 'junk' DNA, or 'dark matter', which at one time they thought didn't do anything. However, they have found that some of this 'dark matter' actually may regulate (or control) the genes themselves! And therefore some of this 'dark matter' can influence the disease by providing an increased likelihood of developing PD based on a person's genetic makeup. He then discussed some of the discoveries he and others have made in this area (exciting stuff!). Basically, the thought was, if we can predict who will develop PD beforehand, we might be able to prevent it.
The great research challenge
As Michael J Fox says, 'Science is hard!' And so is drug discovery. Why has it been so difficult to develop a new therapy? Well, the Parkinson's disease process itself is complex (affecting more than just the dopamine centers of the brain). Also drug trial design is challenging for PD. Trials require large numbers of patients over long periods of time. Not only that, it has to be compared to control subjects (those in the trial without the disease). It was then stressed that we need 'biomarkers' in order to help shorten the discovery complex. Biomarkers are things that one can test for in an individual that can accurately tell whether or not a person has or will develop a disease. We are working toward that goal - exciting things have been happening recently in this area - but we are not there yet.
Developing a new drug is expensive! 'Brain' type drugs take 35% longer to develop, and only 8% of those actually make it to the patient! What astounded me was this fact: The cost for one successful drug, if you include all research and failed drugs - $5 BILLION! And even without failures, it still costs around $200 million for PD drugs!
Can existing drugs be re-purposed for PD?
This means using a drug already developed and in use for another disorder - in this case, Parkinson's. Why? It's a potentially cheaper and faster approach since the drug doesn't have to be created from scratch.
He then discussed a few drugs that are being looked into using this approach, including - believe it or not - a common asthma inhaler drug that could possibly thwart PD!!
The possibility to repair the brain in PD?
This is the 'holy grail' of PD research - and of most interest to us who have the disease now. And that is a way to 'repair' the brain by replacing the dopamine cells lost to PD.
This might be possible because of a discovery found by a scientist named Dr. Yamanaka - who is called the 'father of the iPS cell'. Basically, he devised a way to take common skin cells and convert them in the lab to BRAIN STEM CELLS! These cells could then be 'injected' (either physically or via a dead 'virus') into the substantia nigra where, as has been shown in lab animals, actually get converted into fully functioning dopamine producing cells! This has the potential to replace those cells lost to PD which in turn would relieve a person's motor symptoms. If I remember, trials have already started on this. Amazing stuff!
Debunking Ten Myths that May Sabotage Treatment of PD
This was presented by J. Eric Ahslkog of Mayo. He first went into a short discussion of exactly what Parkinson's Disease was. Then he went into the ten myths as he saw them:
Myth #1 Levodopa stops working after a few years
In reality it never stops working (in PD patients)! Rather, over 10 to 20 years the response may be less dramatic.
Myth #2 Almost everyone develops disabling dyskinesias on Levodopa
Dyskinesias are the 'wiggly' movements that you see in Michael J. Fox - not tremor. What that really reflects is an excessive levodopa response. And that can usually be fixed by regulating the amount and timing of a person's levodopa intake. And it may never become problematic despite many years on levodopa.
Myth #3 Dyskinesias are worse than parkinsonism
He stressed that dyskinesias, although a nuisance, usually these are not painful, and therefore are not problematic because they can almost always resolve themselves with reduction of levodopa doses.
Myth #4 Levodopa should be saved for later... i.e. don't start it until doing badly
I have to admit, when I first was diagnosed with PD, this was my thought exactly. But as I researched the disease, I found out this myth has been debunked. There is no evidence that the best responses can be saved! Any decline in the benefit of using levodopa is primarily related to how long a person has had PD. Why deny yourself the benefits (and better life) of using levodopa now?
Myth #5 The levodopa dose should be limited... but why?
I myself still sometimes think this way - "Am I taking too much?". But over a six-year levodopa trial, the folks on the low dose had poorer control of their parkinsonism than those with the higher dose.
Myth #6 Carbidopa / Levodopa should be taken with meals
I knew the answer to this myth right away! No, levodopa should NOT be taken with meals, because it competes with protein found in the food you are eating. Rather, it should be taken >= 1 hour before meals or >= 2 hours after a meal.
Myth #7 Controlled-release levodopa (Sinemet CR) is the preferred therapy
Again I knew the answer to this right away - in fact I think the CR in Sinemet CR really means 'Crappy Release'! The fact is, the CR formula is slower to kick in and more erratic. Not only that, it has a more complex interaction with food. That's not to say it's not useful - in my case, I use it at bedtime to help keep my symptoms from coming back while I sleep (a common use of it). But in all other cases, immediate release Sinemet is the preferred therapy. (He did mention the new Rytary levodopa form and the differences it poses, but I won't go into that now)
Myth #8 The dopamine agonist (DA) drugs are nearly as effective as levodopa
Ha! Another one I knew right away! Truth is, although useful, dopamine agonist drugs not nearly as effective as levodopa itself in controlling symptoms. In fact, few can get by with just using DA's alone for more than a few years.
Myth #9 Levodopa disrupts sleep
Not true! In fact, levodopa usually helps with sleep and insomnia - especially if one is waking up in the middle of the night with symptoms. Adequate levodopa is the best sleep aid for PD.
Myth #10 We have drugs that may slow PD progression
In controlled PD drug trials, there has been no evidence for any slowing of PD progression... but there is evidence that regular vigorous exercise may slow PD progression! Now I will say that I think there are some drugs and supplements that are being studied that may slow down disease progression - that is why I take the supplements that I do. But he emphasized that there is no proven evidence that conclusively says they do.
The rest of his talk was really on how regular vigorous exercise may not only slow progression, but has been shown to actually maintain or increase brain/hippocampai volumes! The hippocampus is used to store short term memory (among other things) and keeping it healthy means we can hopefully keep our memories and fight any PD induced dementia. All in all, an interesting talk. So keep up the exercise! 1...2...3..4..., 1...2...3...4...
Managing Non-Motor Symptoms of PD
This was presented by Christos Sidiropoulos of MSU. I personally thought it was more geared toward doctors and clinicians rather than patients; but I still gleaned quite a bit from the discussion.
There is a lot of talk about Parkinson's motor symptoms, but not that much on the non-motor symptoms. It is a hugely under-recognized and under-reported topic. In fact, these symptoms may predominate the early and late stages of the disease.
He then spoke on a number of topics in this domain:
This includes such things as loss of smell, visual hallucinations, impaired color vision, and even pain! Did you know 30-50% of PD patients have pain but a lot of these are never reported? This can usually be helped with optimization of levodopa therapy along with Botox or pain relievers such as NSAIDS (such as Aleve).
This includes such things as anxiety, depression, apathy, fatigue, psychosis, and impulse control disorders. He mentioned that some of these can be more debilitating than the actual disease itself! Most of these can be controlled via depression/anxiety drugs (commonly called SSRI's); and since impulse control disorders are usually side-effects of using dopamine agonists, regulating or eliminating those can help resolve that issue.
Apathy was something I had read about but never thought about much. This is when a person simply stops wanting to do anything - no longer wants to go out, or work on their hobby, or talk to people, etc. So this part of the discussion I found extremely interesting - so much so I began to think about myself and if I had experienced anything like this! It's definitely something I - and my wife - need to keep a look out for.
These (including cognitive impairment and dementia) may affect up to 80% of PD patients after 20 years of having the disease. Again, he discussed various drugs that can be used to help control these symptoms - although the benefit varies.
I know this to be a fact; ever since I have been diagnosed I've had trouble sleeping (resulting in even more fatigue). It's a very common disruption for almost all PD patients - up to 90% may be affected. It can significantly affect quality of life, mood and even cognitive performance. He then discussed some things that can help, such as: Better sleep hygiene, light therapy, drugs, melatonin, and reducing PD symptoms (by better managing levodopa therapy or even using Deep Brain Stimulation).
Autonomic nervous system (ANS) dysfunction
I knew about these, but there is not much discussion on them out there. The Autonomic System in your body controls those things that you don't need conscious thought to do - heart beat, digestion, breathing, etc. The issues with dysfunction of this system in PD include urinary dysfunction, erectile dysfunction, gastrointestinal dysfunction, cardiovascular dysfunction, and others (like orthostatic hypertension or even dysfunctional sweating!) A lot of these are very common among PD patients - in fact gastro issues, such as constipation and delayed gastric emptying, are reported in 80-90% of patients. Most are simply a result of the disease progression - turns out the basil ganglia is involved with a lot of these ANS functions, and that is right where PD starts. He then discussed some ways to combat these issues - some with drugs, other with more common things like extra fiber, speech and language therapy, drinking more water, etc. Bottom line is that this is a hugely under-reported problem, and if one is experiencing any of these they need to bring it up with their neurologist, because there are ways to help!
Up to 90% of PD patients are affected at some time with speech issues, including slurred speech or talking too softly. Again, there are ways to compensate; first make sure the person has an adequate level of levodopa, because this has a profound affect upon a person's speech centers. Also, use of the LSVT-LOUD speech therapy can and has helped greatly.
Mental Health Issues: Coping with Anxiety, Depression & Sleep Issues and What You Can Do About It
I'm not going to go into extreme detail on this session presented by Barbara Fisher, but just to say that it dealt a lot with sleeping - the stages of sleep and how you can help get and stay asleep better. She also talked a lot about relaxing (even using self hypnosis) and mindfulness therapy - basically being kind to yourself and to others, and getting rid of negative thoughts. Staying de-stressed is important, because we all know that stress just makes our PD symptoms worse! She emphasized there are always options for different situations, and we parkies need to be aware of that. But doing these things is NOT easy and it takes practice!
The Role of Rehabilitation in Managing Parkinson's Disease
This was put on by someone I know well - Mercy Health Hauenstein! The basic premise of this talk was to discuss and show how rehabilitation services (such as speech therapy, swallowing therapy, occupational therapy, and physical therapy) can help with or even restore a parkie's quality of life. It ended with a talk about the LSVT BIG and LSVT LOUD therapies - if you wish to see more about this, go to http://www.lsvtglobal.com.
The other side of the coin
I truly enjoyed the symposium and got a lot of information from it, and would encourage everyone to attend this next year. However, there is another side of the coin, so to speak. How can I put this?? After the day was over, I felt drained and, frankly, somewhat depressed. "You? Tom?? Mr. Optimistic??" Yes, even though I preach to try to be optimistic and enjoy life with PD, I am human just like the rest of you and there are times where even I get kinda melancholy. Why? During the conference I was reminded time and time again about just how ugly this disease really is - not only from the seminars presented, but also seeing lots of other PD patients there who were more advanced than I currently am in the disease process. It reminded me also, unless that cure is found, of what I am in store for in the future. And that is not only mighty depressing but humbling.
I'm happy to say, though, that I've since 'recovered' and remembered that we need only take one day at a time and not worry about the future. I was reminded of this today by the horrible events that transpired in Las Vegas - you just never know when 'your time' will come - so why worry about the future? As Jesus said, "You have enough problems for today, so why worry about tomorrow? Tomorrow can take care of itself."
And so, I say that, not only to everyone out there, but to myself also. Therefore enjoy your day, and don't worry too much! Thanks for reading!! Till next time...
Note: For more on the conference I just attended, go here at Michigan Parkinson's Foundation.