PRIMER ON PARKINSON'S DISEASE
PRECIS
Dopamine (levodopa) is a master neurotransmitter that is important for a number of physical, physiological, and psychological functions. With Parkinson’s Disease (PD) the dopaminergic brain cells begin to deteriorate and lose their ability to produce this vital neurochemical. Many Parkinson’s researchers now believe “clusters” of a protein, alpha-synuclein, may play a role in destroying the dopamine producing neurons. As dopamine diminishes, so too do the functions it mediates, from movement to mood, and cognition to coordination. Parkinson’s is a chronic, variably progressive condition, currently without a cure and, ultimately fatal. The annualized economic burden of PD is enormous ($25 billion direct and indirect costs in America alone). Individuals can spend upwards of $17,000 a year on medications. The tab for deep brain stimulation surgery (another advanced form of treatment but not a cure) is around $100,000. Worldwide, the disease affects nearly 10 million people. In Utah the growth rate of PD is alarmingly high (10 year growth rate of 31% in the over 65 population). Feb 1, 2015 Parkinson’s became a reportable disease in the state. Using census data and population occurrence best estimates there may be upwards of 60-90 people in Iron County who are 60 years and older whose lives are affected by Parkinson’s. Tremendous progress has been made toward a better understanding of the disease and, the more that is learned, the more complex Parkinson’s turns out to be, and the greater the challenge in finding a cure. Since advancing age is a primary risk factor and since it takes 12 (often more) years of testing for a new pharmaceutical to reach drugstore shelves, there is little hope that the current generation of people with Parkinson’s will ever be cured. For us, the Holy Grail is to find a way to slow the progression of the disease.
NARRATIVE
Parkinson’s Disease (PD) is a chronic, variably progressive neurodegenerative disease that gradually, but relentlessly erodes a large number of essential body functions. These effects include drastic changes in the ability to move normally (sometimes a complete loss of movement), compromised regulation of involuntary bodily activities and, even changes in facial expression and in personality. Due to its common association with certain causes of death, PD is regarded as ultimately fatal. However, PD is not an immediate death sentence, it is a life sentence. Since the number one risk factor is advancing age and people are generally living longer, some experts are sounding the alarm that this malady is emerging as a world health concern.
For the nearly 1 million people with Parkinson’s in America alone (10 million worldwide) and the 50+ thousand (Americans alone) who will join them this this year, the disease remains incurable.
It has been 50 years since the biomedical community declared it would have a cure for Parkinson’s Disease (PD) in 5 years. Yet, still we wait and we hope. It’s not that some of the keenest minds in medical science haven’t devoted whole careers to finding that cure, nor is it that funding (albeit never enough) hasn’t been applied to a heroic effort to uncover the secret this disease keeps so carefully guarded. For some of the reasons mentioned in the next paragraph, clinical trials have yet to produce a medication that even slows the progression of PD to say nothing of finding a cure. So we wait and we hope. Surely, the past 50 years have given the medical sciences some valuable insights, something to point biomedical research toward better treatment and ultimately a cure for Parkinson’s.
In truth, what has been learned about Parkinson’s in the past 50 years could fill volumes and will indeed be valuable knowledge for improved treatments and possibly lead to a cure at some future date. That said, the single-most important lesson learned in the past 50 years, and the reason PD remains both incurable and unrestrained to advance at its own pace, is that PD and its variants are astonishingly more complicated than ever before thought. No two cases are the same and “parkinsonism” (a combination of symptoms often found together with PD) may also be found in a number of other diseases some of which are fatal in as little as one year. Because of the tremendous variation in symptoms, there is a saying in the medical community: “After you’ve seen one case of Parkinson’s, you’ve seen one case of Parkinson’s.” A vast majority (90+percent) of PD cases are idiopathic (no known cause). Researchers seem to be coming to a consensus that idiopathic PD is a complex interaction between advancing age, environment, and genetics making some people more susceptible to any one or a combination of environmental risk factors while others are resistant to the same risks. It’s not unreasonable to expect the name Parkinson’s Disease will someday be replaced by a more descriptive term such as Parkinson’s Spectrum Disease.
In spite of the veritable constellation of possible symptoms, one thing all people with Parkinson’s do have in common is the death/dysfunction of brain cells that produce a vital master neurochemical, dopamine. Dopamine is in one way or another tied to nearly every essential human function from movement to mood. PD researchers are focusing on a “rogue” protein, alpha-synuclein, as the substance that destroys the dopaminergic neutrons in the brain of someone with PD. Physical symptoms of the disease and side effects of its medications are the most easily identified (tremors, rigidity, uncontrollable, jerking movement, imbalance, freezing, slow or lack of movement, loss of speech). However, PD can also affect autonomic nervous system functions (blood pressure regulation, digestion, swallowing, genitourinary functions). Patients often describe PD-related fatigue is an overwhelming forced surrender of body, mind and spirit. It’s fatigue at a cellular level…at the very core of one’s being.
About 40 percent of people (some experts say more) with PD also experience dystonia – painful, prolonged muscle contractions that cause involuntary repetitive twisting and sustained muscle binding and cramping.
Keeping in mind that depression and dementia are typically under-reported, it is estimated that over half of those with PD will experience depression and 50-80 percent will experience some level of dementia. PD and certain of its medications may also cause psychoses, such as hallucinations and delusions. These can often be managed through careful changes in one’s medications in consultation with an appropriately trained medical professional. PD is an opportunistic disease that can make pre-existing conditions worse, erode friendships and disrupt families.
Although the way in which medication is administered has become markedly improved, and some new drugs have been added, the main PD medication itself - the centerpiece of today’s PD treatment - is in fact one of several versions of the same drug that was administered five decades ago, dopamine replacement therapy. It should be noted that even the best of treatments just mask the symptoms while the disease continues to progress. Due to attrition mentioned in the next paragraph, there is a measure of disagreement within the medical community about when to initiate dopamine replacement therapy.
Typically with time, medications become less effective, dosages need to be increased, and complimentary medications are added. The complete approval process for new drugs to reach pharmacy shelves is 12-plus years. Every day, hour by hour, people trying to manage PD often find it akin to trying to gain some footing while navigating a vessel on a roiling sea to an unknown destination. Well within a decade of diagnosis, medications often develop side-effects of their own, sometimes worse than the disease itself. Ultimately, medications will likely lose their effectiveness altogether. It has been noted in the literature that even the technologically advanced deep brain stimulation surgery (for which a large number patients will not qualify) has certain side effects, and a “shelf life” of its own.
It is not uncommon for Parkinson’s patients to spend $17,000 a year out-of-pocket for medication. The Parkinson’s Disease Foundation reports the annualized direct and indirect costs for the nearly one million Americans with PD is nearly $25 billion. While advancing age is the number one risk factor (sharp rise in occurrence after age 60) 5-10 percent of cases diagnosed are age 50 or under. Early onset PD has an entire set of social and occupational concerns of its own owing to the relatively young age of the patient. Typically, by the time someone is diagnosed, over 60 percent of the dopaminergic brain cells have already died. So again, we wait and we hope. What, if anything, can be done now that might actually alter the path of this disease and perhaps slow its progression?