Parkinson’s disease: What it is and possible treatment
Parkinson's disease is a prevalent disorder that affects approximately 40-1000 people per 100,000 with increased occurrence in older individuals. It is characterized by progressive neurodegeneration that can manifest in early stages as mild cognitive impairment and moderate motor dysfunction, rigidity and tremor. As the disease progresses, the severity escalates as well. This then includes falls, difficulty swallowing and neuropsychiatric complications including psychosis. this psychosis can occur in up to 75% of cases of this disease (Kitten et al, 2018).
What is this disease?
Parkinson’s disease is a chronic, degenerative, neurological disorder that affects one in 100 people over age 60 years. While the average age of onset is 60, there have been people diagnosed as young as 18 years. There is no objective test or biomarker for Parkinson’s disease so the rate of misdiagnosis can be high, especially if the diagnosis is made by a non-specialist. It is estimated that at least five million people worldwide are affected by this disease.
Parkinson’s was first characterized by an English doctor, James Parkinson in 1817. Now we recognize this disease is a disorder of the central nervous system in the centers that produce dopamine. Because the causes of this disease are unknown there is no scientifically validated preventative course to decrease the risk. While some studies do not definitively link the factors under investigation they do highlight areas where further study is needed (MJF foundation, 2018).
Parkinson’s disease is traditionally classified as a movement disorder due to signature motor deficits. Some of these include rigidity, abnormal diminished motor activity, tremor, and postural instability. They occur due to the loss of dopaminergic neurons in the midbrain. For many years levodopa was drug of choice for this disorder and other issues were treated symptomatically.
Now research is reaching the point of discovering the main contributor to Parkinson’s. One of these is metabolic impairments such as insulin resistance and mitochondrial dysfunction. This study found a promising approach in treating Parkinson’s. Mechanism of action studies may help to connect the dots as it were to explain how modulation metabolism might promote neuroprotection (Quansah et al, 2018).
Promising research for treatment
Polyunsaturated fatty acids are generally considered to be essential fatty acids retrieved from the diet and necessary for normal physiology. Several studies conducted on both human and rodents suggest polyunsaturated fatty acids vary with gender. It is thought that this difference due to the hormonal differences between the two genders. Brain lipid metabolism relies on a complex integration of diet, peripheral metabolism, sex, genetics, and uptake into the brain. It has been found brain polyunsaturated fatty acids contribute to homeostasis and regulate their function in health and disease, especially their role in neuroinflamatory cascades. In some neurological conditions, polyunsaturated fatty acids metabolism is altered in the brain. There are several drugs that target the brain that appear to do so via altering the brains lipid metabolism. Further research needs to be conducted to find the detailed mechanisms in order to find novel therapies (Layé et al, 2018).
The number of interventions for treating motor symptoms in Parkinson’s disease continues to expand. Evidence-based medicine recommendations are designed to assist a treating doctor in deciding which one to use for an individual patient. Some of these recommendations have also been utilized to establish regional and national guidelines. Unfortunately, not all medical recommendations are up to the scrutiny. One of these was dopamine agonist- the study done didn’t provide a positive result. Even after the study of pramipexole there were safety issues so it was noted as not useful. Yet levodopa preparations like Levodopa ER (extended release) and levodopa/carbidopa IR (Sinemet Immediate release) both continue to be clinically useful for this disease with no safety concerns. Many new options exist for treating motor symptoms of Parkinson’s disease. Evidence-based medicine is just one strategy that is used to treat individual patients. To date, however, there is no intervention that will stop or prevent disease progression (Fox et al, 2018).
And still the goal is unreached
Investigators studying Parkinson’s disease have are getting increasingly interested in studies that have been shown that lipid disruption in the brain may contribute to the formation of the disease. Their work found that the enzyme SCD that helps generate oleic acid was protective. This means this could be a promising target for treatment. And while this study did not use them in the clinic, there are multiple inhibitors of SCD that can be used in research labs. It will require further testing to determine how well it works in human testing (Fanning et al, 2018).
A crucial unmet need for patients with Parkinson’s is a disease-modifying therapy. This is particularly urgent considering the number of affected people is set to double by 2040. An inadequate understanding of the relative relationship and sequence of factors involved in the pathogenesis of Parkinson’s (mechanism occurring in the development of morbid conditions in the development of the disease. The research field for Parkinson’s is now questioning the accuracy of considering this disease as a single entity. It has been suggested that it is actually an umbrella term given to a large cluster of disorders. This study argues that if research programs continue to culminate in clinical trials that target a single pathogenic mechanism in groups of people they are unlikely to yield disease-modifying results (Johnson et al, 2018).
Difficulty for development of effective therapies for Parkinson’s disease is the lack of sensitive and objective progression measures. There has beea n push to make use of digital technologies like a smart phone to gather ‘real-world’ information concerning gait and motor function of the patient. We are at a juncture to develop pharmacological treatments based on knowledge of disease pathology and genetics to potentially slow the progression of Parkinson’s. Unfortunately, none of these new agents have produced enough information to convince industry and governmental sponsors to invest in phase 3 clinical trials. We can remain optimistic with the pace of change in the development of therapeutics for Parkinson’s. This progress will lead to the first treatment that slows Parkinson’s within the coming decade (Sardi et al, 2018).
Fanning, S. et al. (2018). New Parkinson’s disease drug target revealed through study of fatty acids. Bringham and Women’s Hospital.
Fox, S.H. et al. (2018). International Parkinson’s and movement society evidence-based medication review: Update on treatments for the motor symptoms of Parkinson’s Disease. Movement Disorders
Johnson, M.E. et al. (2018). Triggers, facilitators, and aggravators: Redefining Parkinson’s disease pathogenesis. Trends in Neuroscience.
Kitten, A. K. et al. (2018). Primavanserin: A novel drug approved to treat Parkinson’s disease psychosis. Innovations in Clinical Neurosciences, 15(1-2).
Layé, S. et al. (2018). Anti-inflamatory effects of Omega-3 fatty acids in the brain: Physiological mechanisms and relevance to pharmacology. Pharmacology Reviews.
Michael J. Fox Foundation. (2018). Parkinson’s Disease causes.
Quansah, E. et al. (2018). Targeting energy metabolism via the mitochondrial pyruvate carrier as a novel approach to attenuate neurodegeneration. Molecular Neurodegeneration, 13(28).
Sardi, S.P. et al. (2018). Targeted therapies for Parkinson’s Disease: From genetics to the clinic. Movement Disorders, 33(5).