By Melle Hsing
Published 10:29 EST, Sat October 9th, 2021
Parkinson’s disease (PD) remains the second most common neurodegenerative disorder characterized mainly by bodily tremors, muscle rigidity, and postural imbalances. But with the rise of many popular topics regarding medical advancements, PD may be a potential target of some widely discussed therapies. This article introduces and discusses a few of the advancements for Parkinson’s disease treatment, providing insight into its pathophysiology
The development of NXL-112
Dopamine is an important neurotransmitter for regulating movement. In PD, the dopaminergic neurons of the substantia nigra degenerate, leading to increased difficulty in motion. Levodopa (L-DOPA) is the typical drug prescribed to combat PD because it provides synthetic dopamine to the brain. However, when L-DOPA levels peak in the blood, this can lead to motor fluctuations – akin to a surplus in movement. This fluctuation, known as peak-dose dyskinesia (or in broader terms L-DOPA induced dyskinesia [LID]), may not be a serious problem for those with early-stage PD, but given the fact that PD will slowly worsen, increasing L-DOPA dosage to match the worsening of the disease will also exacerbate LID. Other than Amantadine, which is often used to treat LID, researchers from the US biotech company Neurolixis have been working on a new drug: NXL-112.
NXL-112 lowers dopamine levels in serotonin neurons, as L-DOPA can be converted to dopamine and released by these serotonin cells, thereby contributing to LID. While this is what researchers expect NXL-112 to do, it is important that this drug does not inhibit the effectiveness of L-DOPA by overly decreasing net dopamine levels. Neurolixis, a US biotech company, partnered up with their funder, Parkinson’s UK, to conduct a study that tested just that. They found no statistically significant reduction in the effectiveness of L-DOPA for PD patients when NXL-112 was also administered.
Stem cell therapy
Given the side effects of L-DOPA, such as the one discussed above, researchers are seeking alternative methods to treat PD rather than having to take even more medications to combat side effects. This aim has led researchers to ask: how do stem cells fit into the picture?
Stem cells are special for mainly two reasons. Firstly, embryonic stem cells and stem cells derived from cord blood can be pluripotent, in which they can differentiate into various specialised cells such as nerve cells. Secondly, stem cells seem to have no limit to mitosis, meaning that they can divide an infinite number of times. Given that there are fewer dopaminergic neurons in PD patients, perhaps stem cells can be injected into the substantia nigra such that they can differentiate into new, functional dopaminergic neurons.
Figure 1: Stained mesenchymal stem cells (“Mesenchymal Stromal, n.d.)
Researchers are particularly hopeful about the use of mesenchymal stem cells sourced from umbilical cord tissue in PD treatments. This type of stem cell is unique in that it does not pose a negative response to the immune system if the patient were immunally incompatible with the donor of the stem cells. Hence, mesenchymal stem cells may be able to help many different patients regardless of immunocompatibility.
One should note that stem cell therapy does not ultimately cure PD. After some time, Lewy bodies (proteins made of alpha-synuclein whose buildup in dopaminergic neurons is thought to contribute to PD) may accumulate again in these newly made neurons and damage or kill them. However, if it means alleviating the patient’s suffering and improving their life quality, then this treatment may very well be worth pursuing.
GDNF
GDNF, which stands for glial cell line-derived neurotrophic factor, is a protein suggested to promote the production of dopaminergic neurons. Studies conducting GDNF trials have hinted at the possibility of GDNF even slowing down the progression of PD. With a sustained concentration of GDNF in the brain, theoretically, even if Lewy bodies were to build up in dopaminergic neurons, there would be enough GDNF to keep promoting the growth of more dopaminergic neurons to replace damaged ones. However, the current studies available are not extremely clear; hence, more research is needed to come to solid findings. An animal study on rats found that short-term exercise could increase GDNF levels in the spinal cord; hence, exercise may also play a role in encouraging GDNF production in humans. Of course, there would need to be more substantial evidence to justify this, but animal studies can sometimes give insight into how humans may react to exercise.
Conclusion
The treatments discussed above may just be one cornerstone of possible treatments for PD in the coming years, given the rapid advancements in medical research. Other treatments such as gene therapies and deep brain stimulation have also been researched, possibly providing an even wider variety of treatments for the future. While some of these proposed solutions do still have their limitations, they provide significant hope for PD patients who may be struggling to cope with the disease.
Melle Hsing Youth Medical Journal 2021
References
Cona, L. A. (n.d.). Stem cell therapy for Parkinson’s disease in 2021. DVCSTEM Blog. https://dvcstem.com/post/stem-cell-therapy-for-parkinsons
McCullough, M. J., Gyorkos, A. M., & Spitsbergen, J. M. (2013). Short-term exercise increases GDNF protein levels in the spinal cord of young and old rats. Neuroscience, 240, 258–268. https://doi.org/10.1016/j.neuroscience.2013.02.063
[Mesenchymal stromal cells]. (n.d.). Stem Cell. https://www.stemcell.com/mesenchymal-stromal-cells-updates-and-debates
Our research achievements so far. (n.d.). Parkinson’s UK. Retrieved August 24, 2021, from https://www.parkinsons.org.uk/research/our-research-achievements-so-far
Promising drug could treat debilitating movement problems in people with Parkinson’s. (2020, March 1). EurekAlert! https://www.eurekalert.org/news-releases/759442
When will there be a cure for Parkinson’s? (n.d.). Parkinson’s UK. Retrieved August 24, 2021, from https://www.parkinsons.org.uk/research/when-will-there-be-cure-parkinsons
Youth Medical Journal 