At the turn of the millenium, actor Michael J. Fox, whom you might remember from the Back to the Future films and Family Ties if you're a certain age, had to depart the cast of the popular sitcom Spin City because he was diagnosed with Parkinson's Disease. I was a frequent viewer of the show (and of course I watched Back to the Future, and so should you) so it was a shock to the system to see a man who was still so vibrant and young have to take a step back from his profession because of that diagnosis. April is Parkinson's Awareness Month, which you can read more about from Fox's foundation and others, and in this post I thought we could learn more about this disorder together as humanity works towards an eventual cure.
What is Parkinson's Disease?
Around one million people in the United States and millions around the world, including celebrities like the late Muhammad Ali and Michael J. Fox, suffer from Parkinson's Disease (PD). According to the Parkinson's Foundation, PD is the second-most common neurodegenerative disorder behind Alzheimer's disease, with men about 1.5 times more likely to develop PD than women. As the population grows and ages, the number of people who will develop and live with PD will also increase, and with medical costs rising, this places a burden on families, the medical system, and society at large.
Parkinson's occurs because of a specific disruption or death in neurons that produce dopamine, which leads to a number of motor and non-motor symptoms. 1, 2 As a progressive disease, symptoms at the beginning of disease manifestation can be mild, but may include tremors that intensify with time, stiff or altered movements, and some speech issues as well according to the Mayo Clinic. At this time, there is no cure for PD, but there are medications and surgical interventions available to help manage the symptoms, as well as physical therapy. Unfortunately, just as with other neurological disorders including Alzheimer's and multiple sclerosis, the best available treatment is to just help patients feel as comfortable as possible as they continue living with their disease.
Evolving Strategies to Diagnose Parkinson's
The holy grail of diagnosis and treatment is to identify specific biomarkers that can help differentiate between healthy individuals and those who might develop or have a particular disease or disorder. The idea is to have an accurate and reliable biomarker that can help detect PD early and change the course of treatment to alleviate symptoms from the onset, perhaps even before mild symptoms show, and also give an idea of how the disease may progress in that individual. 1, 2 Similarly to multiple sclerosis diagnosis, PD diagnosis may involve using the cerebrospinal fluid (CSF) to detect specific biomarkers. 3 Organizations including the American Parkinson Disease Association understand the value of biomarkers and are funding research to explore existing and novel biomarkers.
Some diagnostic biomarkers include the tremors and possible changes in mood or ability to make everyday movements easily. Imaging systems, including positron emission tomography (PET) and magnetic resonance imaging (MRI) can detect changes in dopamine production and uptake or physical changes in the abundance of certain types of neurons. 1, 2 On the biochemical side, it may be possible to detect changes in abundance for certain microRNA sequences or protein markers. One of the most common proteins studied in PD is alpha-synuclein (SNCA), which is produced in various parts of the brain and can form protein aggregates found in Lewy bodies that are characteristic in a large proportion of PD patients. 2 Another potential biomarker is the neurofilament light chain, particularly if found in the serum, could serve as a predictive biomarker in PD in conjunction with SNCA found in CSF. 4 Since, like other neurodegenerative disorders, the onset of PD is associated with neuroinflammation, measuring pro-inflammatory cytokines such as TNF-alpha and IL-10 could be instructive as well. 1
Treatment Options For Parkinson's
PD manifests in different ways for each afflicted individual, so individual treatment strategies have to adapt to each patient's unique symptoms and circumstances. Physical therapy is often given to patients to help improve balance and slow the deterioration of motor ability. Medications are designed to help alleviate symptoms that disrupt normal movements, and are based on either introducing dopamine or substituting for the effects of dopamine through indirect mechanisms. In some cases, surgery may be employed to manipulate the part of the brain that is causing the involuntary movements associated with the patient's PD through removal of a lesion or deep brain stimulation through electrodes directly implanted into the brain.
One of the most common drugs used in PD is called levodopa, which serves as a metabolic precursor of natural dopamine and is directly converted into dopamine by the patient's own neurons. 2 Levodopa is used in combination with carbidopa, which is a dopamine decarboxylase inhibitor that prolongs the life of dopamine in the system. There are also drugs that mimic the effects of dopamine and also inhibit monoamine oxidases to disrupt their ability to metabolize dopamine and reduce reactive oxygen species generation and protect neurons from oxidative damage. 2 In the future, some potential PD medicines may include inducers of autophagy in order to clear the SCNA and other protein aggregates to prevent apoptosis of affected neurons. 2 Perhaps even further in the future, a cure may be developed using gene therapy to introduce dopamine or help manage movement-related symptoms, but we aren't there yet.
Raising Awareness For Parkinson's Disease
While treatments for PD have improved and there are many research directions being undertaken to trend towards an actual cure, we still need to understand the difficulties suffered by PD patients and find ways to help them achieve a higher quality of life despite their ailment. There are multiple foundations involved in raising funds and awareness to continue researching PD as well as improving the lives of patients through a network of education and resources.
For example, the Michael J. Fox Foundation highlights several fundraising opportunities, including charity concerts and walk/run events to drum up donations. There are events to educate PD patients and their families about research advances and accessibility to resources, as well as opportunities for PD patients to join studies and trials to help research along as direct participants. The Parkinson's Foundation has an event called #Take6forPD that provides many educational talks and also to register patients to participate in a global genetics study and other studies. As with all things, nothing is impossible when we all work together towards a brighter future.
References
- Li T & Le W (2020) "Biomarkers for Parkinson's Disease: How Good Are They?" Neuroscience Bulletin 36(2):183-194.
- Emamzadeh FN & Surguchov A (2018) "Parkinson's Disease: Biomarkers, Treatment, and Risk Factors." Front Neurosci 12:612 (Epub).
- Parnetti et al. (2019) "CSF and blood biomarkers for Parkinson's Disease." The Lancet Neurology 18(6):573-586.
- Liu et al. ((2022) "Neurofilament light as a biomarker for motor decline in Parkinson's disease." Front Neurosci 16:959261 (Epub).
