Despite the fact that, in terms of prevalence of neurodegenerative diseases, Parkinson’s Disease is only surpassed by Alzheimer’s Disease, there remains no cure. Treatments are purely palliative, seeking to manage symptoms and make day-to-day life easier for sufferers. Care options range from physical therapy to surgery, though some drugs have been developed that appear to alleviate the physical symptoms. However, none of these options slow the progression of the disease.

Dopaminergic neurons such as those of the substantia nigra are more susceptible to the neurotoxic Lewy body aggregates than other neurons in the brain. This causes an overall reduction in the amount of dopamine, the brain’s “motivational chemical”, which in turn affects the initiation and execution of movement. Consequently, L-DOPA (a precursor to dopamine) injections remain the most common treatment for those suffering with PD. L-DOPA is then converted to dopamine by dopamine decarboxylase. Whilst effective at treating early-stage Parkinson’s, patients need progressively stronger doses as the decarboxylase enzymes become insensitive to the dose. There are other side effects, such as unintentional movement (dyskinesia) and nausea.

There have been more recent reports of success in treating Parkinson’s with drugs that relieve oxidative stress. One such drug, D-512, was found to be more effective at relieving symptoms than current medications prescribed to patients (Lindenbach, 2017). Though not yet tested in clinical trials, results from animal models offer new hope for patients.

Other research suggests that drugs already approved for other conditions can also be utilised in treating Parkinson’s patients. Exenatide is a glucagon-like peptide-1 agonist used in managing diabetes. Results from a phase two clinical trial showed that those that received injections of the drug had a slight improvement in motor ability whilst those in the control group worsened over the same time period (Athauda et al., 2017). The study was small, though the results are significant enough to warrant further research.

Similarly, it has been found that those with early-onset Parkinson’s may benefit from treatment with folinic acid, usually used in treating bowel cancers (Lehmann et al., 2017). The trial was conducted in a Drosophila model of Parkinson’s, and was specifically associated with those carrying mutations in the pink1 gene. Previous research had shown that folinic acid had a neuroprotective effect that slowed the progression of the disease. The fact that the drug has already been approved for clinical use, even for a different disease, is of great benefit as it streamlines the approval process.

Drugs are not the only component of the Parkinson’s treatment repertoire. Other, lifestyle changes can help alleviate many of the physical symptoms of the disease, or at least slow their progression. A recent study found that just two-and-a-half hours of exercise a week was enough to confer a benefit (Rafferty et al., 2017). Other studies lend support to this finding: patients that exercise are also less likely to suffer falls (The University of Stavanger, 2017).

There are other, more invasive procedures that are currently in use. Deep brain stimulation, for example, involves the insertion of an electrode in the patient’s brain to deliver electrical pulses to certain areas of the brain (National Institute of Neurological Disorders and Stroke, 2017). The procedure is generally used as a last resort, though recipients generally experience significant improvement in motor symptoms post-surgery.

Nevertheless, more effective treatments – and preferably, cures – are still necessary. These will come about through years of intensive research, both into the basic biology underpinning the disease and clinical trials looking at existing treatment options. Until then, the only option is to reduce the suffering of Parkinson’s sufferers through palliative care.

References:

Athauda, D. Maclagn, K., Skene, S.S., Bajwa-Joseph, M., Letchford, D., Chowdhury, K., Hibbert, S., Budnik, N., Zampedri, L., Dickson, J., Li, Y., Aviles-Olmos, I., Warner, T.T., Limousin, P., Lees, A.J., Greig, N.H., Tebbs, S. and Foltynie, T. (2017) Exantide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. The Lancet http://dx.doi.org/10.1016/S0140-6736(17)31585-4

Lehmann, S., Jardine, J., Garrido-Maraver, J., Loh, S.H. and Martins, L.M. (2017). Folinic acid is neuroprotective in a fly model of Parkinson’s disease associated with pink1 mutations. Science Matters doi: 10.19185/matters.201702000009

Lindenbach, D., Banibrata, D., Conti, M.M., Meadows, S.M., Dutta, A.K. and Bishop, C. (2017). D-512, a novel dopamine D2/D3 receptor agonist, demonstrates superior anti-parkinsonian efficacy over ropinirole in parkinsonian rats. British Journal of Pharmacology DOI: 10.1111/bph.13937

National Institute of Neurological Disorders and Stroke (2017). https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Deep-Brain-Stimulation-Parkinsons-Disease-Fact

Rafferty, M.R., Schmidt, P.N., Luo, S.T., Li, K., Marras, C., Davis, T.L., Guttman, M., Cubillos, F. and Simuni, T. (2017). Regular exercise, quality of life, and mobility in Parkinson’s Disease: A longitudinal analysis of National Parkinson Foundation Quality Improvement Initiative Data. Journal of Parkinson’s Disease 7:DOI: 10.3233/JPD-160912

The University of Stavanger (2017). “Exercise helps prevent falls in Parkinson’s patients.” ScienceDaily.  <www.sciencedaily.com/releases/2017/03/170301083706.htm>.

About the Author

Rachel Murray-Watson is currently pursuing a PhD in Cambridge University. Rachel obtained a first class honours (BSc) in Biological Sciences from Imperial College, London. Her thesis was on “Modelling the Spatial Spread of Gene Drives” and she won the Howarth Prize for excellence in plant sciences. Rachel won the Institute of Biology’s prize for 1st place in biology in the national examinations in Ireland. Her current area of research is mitigating the impact of communicable agriculural diseases by developing effective control strategies.