Stem Cell Transplants for Alzheimer's and Parkinson's Disease

Introduction

Expectations from medical researchers to develop a breakthrough treatment for the most widely occurring neurodegenerative ailments in the French population — namely, Parkinson's Disease (PD) and Alzheimer's Disease (AD), which affect nearly 200,000 and 900,000 individuals, respectively — are now higher than ever before. Considering the nation's aging population, these figures are expected to continue climbing, with around 1.3 million persons projected to be diagnosed with Alzheimer's by the year 2020 (Alzheimer's Association, 2015). PD represents a neurodegenerative condition marked by dopaminergic neuron degeneration within the pars compacta area of the brain's substantia nigra (Hwang, Gill, Pathak, & Subramanian, 2018). This degeneration occurs due to the deterioration of dopamine-generating nerve cells within the substantia nigra, a mesencephalon area responsible for controlling movement. The degeneration leads to lower levels of the neurotransmitter dopamine within the patient's brain, which is vital to the regulation of body movement.

Parkinson's clinical symptoms emerge when roughly 70 percent of dopamine-producing neurons have been damaged. These symptoms include bradykinesia (a slowing down of physical movement), tremors or shaking, muscular rigidity or stiffness, pain, and impaired coordination and balance (i.e., postural instability). Disease prevalence is approximately 1.5 times higher in males than in females; furthermore, PD rates increase with age, affecting around one to two percent of individuals aged above 70 years. While its causes have yet to be fully determined, several research scholars suggest the disease emerges as a reaction to a combination of genetic and non-genetic factors (Goodarzi et al., 2015).

Alzheimer's has been identified as one of the most common causes of dementia. Despite many decades of research on the disease, a standard Alzheimer's-modifying treatment has yet to be developed; the medications currently approved are able to provide only symptomatic relief to patients (Bali, Lahiri, Banik, Nehru, & Anand, 2017). Roughly 5.3 million citizens of the United States suffer from Alzheimer's, of whom 5.1 million belong to the above-65-years age group. The remainder, aged below 65, have premature disease onset. By the year 2050, the number of Alzheimer's patients in the nation is estimated to rise by as many as ten million — growth largely attributed to the aging of the baby boomer generation. At present, it is estimated that a new case of Alzheimer's develops every 67 seconds (Alzheimer's Association, 2015).

Several brain neurons gradually begin to degenerate, particularly in the hippocampus, which is the site of short-term memory storage; this degeneration progressively spreads throughout the brain. The tau protein and the amyloid-β peptide are considered responsible for the degeneration. The latter, a naturally occurring protein in the human brain, accumulates until senile or amyloid "plaques" are formed. This buildup proves harmful to nerve cells. Additionally, it is linked to structural modifications in the tau protein, which is involved in neuron structure. Consequently, brain neurons become disorganized, resulting in cell death and neurofibrillary degeneration. This extremely slow process of neurodegeneration begins affecting a patient's brain several years before the earliest disease symptoms emerge (The Research Journal, 2017).

Stem Cell Transplants and Parkinson's Disease

As of now, there is no standard intervention for PD; the existing approved medicines and interventions focus on reducing symptoms. These interventions include the oral administration of dopamine receptor agonists and L-DOPA (L-3,4-dihydroxyphenylalanine). Deep brain stimulation of the globus pallidus and the subthalamic nucleus using electrodes is also a known intervention for addressing PD symptoms. The pharmacological approach described above is based on L-DOPA uptake and the inhibition of dopamine degradation through the use of dopamine agonists. Many hospitals begin treatment with dopamine receptor agonists before progressing to L-DOPA. The agonists are also regarded as useful in the later stages of Parkinson's disease as a complementary therapy alongside L-DOPA, working by stimulating dopamine receptors at both pre- and post-synaptic sites. Levodopa is one such PD medication, used to relieve the effects of dopamine deficiency; however, its therapeutic effect diminishes considerably after approximately three years (Goodarzi et al., 2015).

Several other drugs are used in the treatment of Parkinson's disease, including Amantadine, monoamine oxidase B inhibitors, anticholinergic drugs, Ropinirole, Pramipexole, and Bromocriptine. Some of these medications — for example, Amantadine — treat PD by stimulating the affected region of the brain. Monoamine oxidase B inhibitors work by stabilizing dopamine levels in the synaptic cleft. Different stem cell types are currently being investigated for use in the cellular treatment of neurological diseases such as PD, stroke, multiple sclerosis, and spinal cord injury. Those being studied for PD are yielding positive results, and both their benefits and drawbacks are being carefully considered (Goodarzi et al., 2015).

Stem Cell Transplants and Alzheimer's Disease

As of now, there is no consensus on how to precisely diagnose or monitor Alzheimer's disease. The lack of uniform diagnostic and monitoring methods has hindered the development of effective AD treatments. Existing therapies include the prevention of neurotransmitter degradation, which provides temporary relief from AD's main symptoms but does not address its pathophysiological burden. Stem cell studies have been conducted to investigate whether stem cell transplants can replace damaged neurons in people with AD, or whether they can secrete trophic factors to protect existing cells. Blurton-Jones et al. investigated whether neural stem cell transplants could reverse memory impairment. By transplanting the cells into mice, the researchers demonstrated that neural stem cells can reduce memory loss and spatial learning deficits, and also boost synaptic density, helping to further reduce symptoms (Bali et al., 2018).

However, some studies have concluded that transplanted cells may activate an immunomodulatory response that causes cytokine secretion and release, which may in turn target the underlying pathology of AD. A pharmaceutical research company, Neuralstem, Inc., recently released comprehensive data on the success of stem cell transplants in mice. According to their results, HK532:IGF1 (NSI-532.IGF) cells improved memory and reduced spatial learning degeneration in mice with AD. For the purpose of generating human IGF1, the company engineered a cortical neural cell for transplant. IGF1 cells are known for their neuroprotective properties. The cells were administered in the peri-hippocampal area over a period of 10 weeks, and the stem cell transplants continued to benefit the mice for up to 14 weeks. These early findings suggest that stem cell transplantation holds genuine promise as a strategy for addressing AD (Bali et al., 2018).

Conclusion

On the whole, stem cell treatment has created great hope among patients diagnosed with multiple degenerative conditions; however, an in-depth assessment of likely risks and risk factors of stem cell-based therapies is essential before widespread approval for clinical administration. For each such therapy, the likely risks to patients must be appropriately assessed, and both the distinct inherent characteristics of the stem cells and the safety information already gathered about similar products must be taken into consideration. Furthermore, external risk factors — such as those related to production, storage, handling, and clinical application — may all contribute to patient risk. In the course of risk assessment, safety-related knowledge derived from similar stem cell-based therapies may prove highly valuable. Established risks, known risk factors, and anticipated risks should all be factored into this assessment process (Herberts et al., 2011).

Further studies are needed to establish the best models for treating both PD and AD. There is also a need to determine the optimal route of administration, dosing, disease stage at intervention, and sources of stem cell transplants, so as to identify the approach that offers the most beneficial therapeutic outcome for patients.

References

Alzheimer's Association. (2015). 2015 Alzheimer's disease facts and figures. Alzheimer's & Dementia, 11(3), 332–384. doi:10.1016/j.jalz.2015.02.003

Bali, P., Lahiri, D., Banik, A., Nehru, B., & Anand, A. (2017). Potential for stem cells therapy in Alzheimer's disease: Do neurotrophic factors play a critical role? Current Alzheimer Research, 14(2), 208–220. doi:10.2174/1567205013666160314145347

Goodarzi, P., Aghayan, H. R., Larijani, B., Soleimani, M., Dehpour, A. R., Sahebjam, M., … & Arjmand, B. (2015). Stem cell-based approach for the treatment of Parkinson's disease. Medical Journal of the Islamic Republic of Iran, 29, 168.

Herberts, C. A., Kwa, M. S., & Hermsen, H. P. (2011). Risk factors in the development of stem cell therapy. Journal of Translational Medicine, 9(1). doi:10.1186/1479-5876-9-29

Hwang, S., Gill, S., Pathak, S., & Subramanian, S. (2018, March 30). A comparison of stem cell therapies for Parkinson disease. Georgetown Medical Review. Retrieved from https://gmr.scholasticahq.com/article/3420-a-comparison-of-stem-cell-therapies-for-parkinson-disease

Railton, D. (2019, February 18). Stem cells: Therapy, controversy, and research. Retrieved from https://www.medicalnewstoday.com/articles/200904.php

The Research Journal. (2017, September 20). Alzheimer's and Parkinson's — the current state of research. Retrieved from