Tuesday, April 22, 2014

Vitamin X, The Third Great Discovery in Parkinson's Treatment in the Past Forty Years

(Adapted from a talk I gave recently to  our local PD support group)

Parkinson's Disease has been afflicting humanity for thousands of years. For most of that time,  not much could be done to alleviate the symptoms, much less halt the ravages of the disorder. In the past forty years or so, there have been three major developments that have changed the way patients experience symptoms of Parkinson’s.

The first discovery came in the mid 1960’s, researchers found the motor symptoms of PD could be alleviated through use of levodopa. These symptoms of Parkinson’s Disease stem from reduction of the ability of the brain to make dopamine, the chemical messenger that enables our brains to communicate with our muscles. When the body is supplied with levodopa, combined with carbidopa  to avoid nauseating patients, the brain can transmute the l-dopa chemically to dopamine, making up for the lost supply. This can mean nearly total control of symptoms, at first. (Sinemet is the medicine's commercial name)

The second great change in symptom management came with Deep Brain stimulation (DBS). This is a surgical procedure that can have dramatic results in patients who are “Good Candidates” (patients who respond well to l-dopa and have no significant cognitive impairments) DBS was approved as a treatment for PD by the FDA in 2002. The procedure is audacious and demanding, but the results can be impressive. Unfortunately, not all patients qualify to have the operation, and for reasons that are not understood, occasionally a good candidate will have bad results.

In fact, both these developments, impressive as they are in technical rigor and in results in terms of improved quality of life, have drawbacks. In the case of levedopa, as time goes on and patients lose more of their capacity to cope with the disease, they compensate by increasing their dosages. This leads to unwanted side effects that are as debilitating as the disease. Among these side-effects are Dyskinesia, excessive unwanted movement, and motor fluctuation, the "wearing off" of the medication that results in the unmasking of tremor, softness of speech, slowness and all the other motor symptoms that the medicine holds at bay.

Not to mention the that medication must be taken regularly throughout the day, at the correct intervals for meaningful relief. Life being what it is, schedules can get messed up.Which means that the patient gets messed up, too. In addition there are Parkinson’s symptoms that seem beyond the reach of levodopa, in particular the loss of sense of balance. Still, the discovery of levodopa as PD therapy has led to great increases in both quality of patients lives, as well as sheer life duration.

Like l-dopa DBS surgery can have great impact on a patient’s symptoms, but it comes with side effects and limitations as well. As with Levodopa, it seems unable to prevent falling. It has little effect on non-motor symptoms, like depression. And of course it IS brain surgery with all the attendant risks of bleeding, infection, etc. It is also blamed for some patients loss of ability to speak clearly, and in certain cases, for actually worsening balance. Also, again like l-dopa, DBS only treats symptoms without affecting the underlying disease.

There is a third exciting development in the treatment of Parkinson’s Disease that is just now coming into its own. It brings significant advantages and promise of hope to the table. It is relatively cheap and freely available. Furthermore, when used correctly, it is without nasty side effects. Almost more exciting, and unlike the first two developments, there is evidence that it is disease-modifying, not merely useful for coping with symptoms. It is wise to consult with your Doctor before you start this approach, but after the initial work is done, you are free to use the treatment as you see fit.

So what is this miraculous PD panacea, and how can you obtain it? It’s Vitamin X... exercise!

 Ten years ago, little was known, or, at least published, about the benefits that exercise can confer on PD patients. In fact, for awhile, the conventional wisdom was that exercise was not a good idea if you had PD. Times have changed.  Exercise is now seen as indispensable PD therapy. What do researchers say as to how to benefit from exercise? Well one, Dr. Jay Alberts (Check out this video, featuring his research) has found the performing “forced” exercise, over and above what you would normally put into a physical activity can enable patients to increase their score in Parkinson’s assessments by 30-35% over a period of a month! If one came up with a drug that did the same tomorrow, they'd be rich and celebrated the World over. It’s true that if patients did not continue their exercise regimes, they would lose the benefit over three weeks time. So what? If I skip taking pills for three hours, let alone weeks, I’m in a world of hurt.

One of the worst aspects of Parkinson’s is the loss of the ability to balance, and the consequent falls this brings on. In addition to being scary and painful in their own right, falls can result in drastic complications, such as broken bones, These can lead to even worse complications, such as infected bedsores, which can be fatal. Ten year ago when someone came to me and said “How can I cope with falling?” all I could do for them was to suggest ways to recover and to get up off the floor. Now we know that various forms of exercise, Yoga, Tai-Chi, and dance can help to recover and preserve a patient’s ability to balance.  And we are lucky enough in Anchorage to have both an instructor of dance for PD and another for Yoga for PD. Both have gotten special training in working with PD Patients and each give weekly classes in these fields.

Exercise may be the only way known to achieve the Holy Grail of Parkinson’s treatment: Disease modification. To slow or stop the progression of this disease has long been an unfulfilled goal of Parkinson’s research . CoQ10, Eldepryl and Azilect have all  been touted as having the ability to slow this disease. None has been proven to make a dramatic difference. According to the Michael J. Fox Foundation “While Teva (maker of Azilect) was praised by members of a US FDA advisory panel and regulators on 17 October for conducting a complex clinical trial aimed at demonstrating that its Parkinson's disease drug Azilect (rasagiline) may slow the progression of the disease, the committee unanimously said the study ultimately failed in providing substantial evidence to back up that claim.” What would such a claim mean if proven? Again, from the Fox Foundation: “Dr Russell Katz, director of the FDA's Division of Neurology Products, noted that US regulators have never approved a treatment for disease modification in any neuro-degenerative conditions. "The effect of disease progression is something that is tremendously important, both from a clinical point of view for patients, but also from a regulatory point of view," he said. "If you tell people in labeling that a drug has an effect on disease progression, you really want to be sure it has an effect on disease progression."If a drug is found to have an effect on disease progression, Dr Katz said it would "change dramatically, not only clinical practice, but controlled trials in the future.”

 Exercise is now seen as a likely way to reach this elusive goal. According to the National  Parkinson’s Foundation:

“There is a strong consensus among physicians and physical therapists that improved mobility decreases the risk of falls and some other complications of Parkinson’s.  They agree that practicing movement—physical therapy, occupational therapy, and participating in an exercise program—improves mobility.  By avoiding complications, you can avoid some of the things that can make PD worse.  Beyond this, we know that people who exercise intensely, for example by doing things like running or riding a bicycle, have fewer changes in their brains caused by aging.  Studies in animals suggest that Parkinson’s disease is also improved by exercise.”

Furthermore there is a clear theory that  explains what exercise may do to foster neuroprotection, the guarding of nerve cells from harm. Exercise increases the level of neurotrophic chemicals in the brain, These are the chemicals that promote the growth of nerve cells. The more of the neurotophic chemicals available, the better the conditions for bolstering  your brain cells. It also appears that exercise allows the brain to use dopamine more efficiently. So you make the most of what you’ve got.

What is the best way to take advantage of this new knowledge of the benefits of exercise?  According to the NPF:

”The best way to achieve these benefits is to exercise on a consistent basis. People with Parkinson's enrolled in exercise programs with durations longer than six months, regardless of exercise intensity, have shown significant gains in functional balance and mobility as compared to programs of only two-week or ten-week durations. However, when it comes to exercise and PD, greater intensity equals greater benefits. Experts recommend that people with Parkinson's, particularly young onset or those in the early stages, exercise with intensity for as long as possible as often as possible.  Your doctor might recommend an hour a day three or four times a week, but most researchers think that the more you do, the more you benefit. Intense exercise is exercise that raises your heart rate and makes you breathe heavily.  Studies have focused on running and bicycle riding, but experts feel that other intense exercise should provide the same benefit. Regardless of your condition, you should always warm up and cool down properly, exercise in a way that is safe for you, and know your limits.  There are many support groups, therapists, and exercise programs who can help with PD-safe exercise and help you to set up your own program if that’s what works best for you.  Be sure to consult your physician.  If your physician is not a PD expert, you can call the NPF helpline (1-800-4PD-INFO) to help you to explain to your physician the importance of exercise so that you and your doctor can put together a plan that will work for you.”

Is exercise a magic bullet against PD? Lab experiments with Rats that were injected with a substance that induces PD-like symptoms, and then exercised showed a lower rate of symptoms than a group that did not have exercise. But the problem is that if exercise were an all-protective panacea against Parkinson’s Disease, how do we explain the fact Olympic Athlete Davis Phinney got the disease?  He was certainly exercising big-time before diagnosis. So, no. We haven’t got a magic bullet. But turn the question around. How bad off would Phinney be if he had NOT been training for the Olympics much of his life? We don’t have any way of  knowing. But the knowledge we do have suggests that his exercising was not a waste of time.

Of the three major developments in the world of Parkinson’s in the past 40 years, it’s hard to say which is the most significant. But there is clearly one which, in its ease of  access, low cost, return on investment, lack of dangerous or otherwise undesirable side effects, and promise of substantial outcomes is in a class by itself. The question for you, given the stakes and the state of the science is what are you waiting for? (h/t @ Dr. Dave Heydrick)


pdwarrior said...

Great post. Thanks for the info

Peter Dunlap-Shohl said...

You're welcome! Now drop and give me 50 :~)