Neurodegenerative diseases like Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS) are among the most challenging medical conditions to treat. These disorders involve the gradual breakdown and loss of neurons in specific areas of the nervous system, leading to symptoms such as memory loss, paralysis, and impaired movement or cognition.
Despite decades of research and billions of dollars in clinical trials, researchers have yet to find a cure for these conditions, and even effective treatments remain limited. As a result, neurodegenerative diseases place a significant emotional, physical, and economic burden on individuals, families, and healthcare systems worldwide.
In this review, Sivandzade et al. summarize the current knowledge of stem-cell-based therapies in neurodegenerative diseases and the recent advances in this field.
The Potential of Stem Cells in Treating Neurodegenerative Disorders
In recent years, regenerative medicine, particularly stem cell therapy, has emerged as an exciting new frontier in the treatment of neurodegenerative diseases. Stem cells have the remarkable ability to become various types of specialized cells in the body. In the context of neurodegenerative diseases, they may be able to repair damaged tissue, replace lost neurons, or create a healthier environment in the brain or spinal cord that helps preserve existing cells.
This unique potential has led researchers to explore whether stem cells could help slow disease progression, reduce symptoms, or even restore lost function in patients affected with these conditions.
Stem Cell Therapy Approaches in Neurological Disorders
Stem cell therapy strategies for neurodegenerative diseases typically fall into two main approaches. The first involves directly replacing the specific types of neurons that are lost during the disease process. For example, researchers aim to generate dopamine-producing neurons for patients with PD or restore damaged motor neurons in people with ALS. The second approach focuses on environmental enrichment, where stem cells are used to support the body’s own repair mechanisms. According to the authors, this could involve delivering neuroprotective growth factors like brain-derived neurotrophic factor (BDNF) or glial cell line-derived neurotrophic factor (GDNF), which help nourish and protect surviving neurons.
Recent research has also explored combining both strategies – using stem cells to replace lost cells while simultaneously enhancing the surrounding environment.
Stem Cell Therapy for Parkinson’s Disease
In Parkinson’s disease, the main issue is the gradual loss of dopamine-producing neurons in a part of the brain called the substantia nigra. This loss leads to symptoms like tremors, muscle rigidity, and slowed movement, usually appearing in people between their 50s and 70s.
Current treatments focus on increasing dopamine levels or using deep brain stimulation to control symptoms. While helpful, these options do not stop or reverse the underlying neuron loss. Stem cell therapy offers a promising alternative by aiming to replace the lost dopamine neurons or protect those that remain.
Recent studies have used embryonic stem cells (ESCs) to produce new dopamine-producing cells that can be transplanted into animal models of PD. These cells have shown the ability to migrate to damaged areas and improve motor function. However, ESCs come with ethical concerns and a risk of tumor formation, which has limited their use in human trials.
Mesenchymal stem cells (MSCs) have also shown potential in PD animal models by helping rebuild damaged dopamine nerve networks. Additionally, induced pluripotent stem cells (iPSCs) – adult cells reprogrammed to act like embryonic stem cells – have recently gained attention because they can be used to generate personalized dopamine-producing neurons without the ethical concerns associated with ESCs. These iPSC-derived neurons have shown promising results in animal models, surviving and integrating into the brain while improving motor symptoms.
Stem Cell Therapy for Alzheimer’s Disease
For patients with Alzheimer’s disease, the situation is more complex. AD is the most common neurodegenerative disease, affecting over 5 million Americans. It leads to memory loss, confusion, impaired judgment, and eventually complete cognitive decline. The disease is marked by the buildup of two harmful proteins in the brain: amyloid-beta, which forms plaques outside neurons, and tau, which forms complex tangles inside them. These protein abnormalities disrupt communication between brain cells and eventually cause them to die. Current medications focus on improving symptoms and slowing progression, but they do not reverse the damage.
Stem cell therapy for AD focuses on restoring lost neurons and improving the brain’s ability to function and heal. Studies using human neural stem cells in animal models of Alzheimer’s have shown that these cells can improve learning and memory, possibly by enhancing synaptic plasticity and increasing the production of proteins involved in cognitive function.
However, challenges remain, including understanding how these stem cells exert their effects and controlling the formation of unwanted cell types. Researchers are currently exploring the use of nerve growth factor (NGF) in combination with stem cells to protect existing neurons and encourage the growth of new ones.
NGF gene therapy has shown promise in early trials and may help amplify the positive effects of stem cell treatment.
Stem Cell Therapy for ALS (Amyotrophic Lateral Sclerosis)
Amyotrophic lateral sclerosis, or ALS, is another devastating condition in which motor neurons in the brain and spinal cord gradually die, leading to muscle weakness, paralysis, and ultimately death, typically within a few years of diagnosis. Most cases are sporadic and occur without a clear genetic cause, though some cases are linked to inherited gene mutations. Because multiple mechanisms may contribute to the disease, including protein misfolding, oxidative stress, and inflammation, it has been extremely difficult to find effective treatments.
Stem cell research in ALS is still in the early stages, but it holds potential. The goal is not necessarily to replace the lost motor neurons – which is extremely difficult – but rather to create a supportive environment that preserves the neurons that remain and slows disease progression.
Some clinical trials have tested the use of MSCs and neural stem cells (NSCs) injected directly into the spinal cord. Results from these early studies suggest that the treatments are safe and may help stabilize function in some patients. In animal models, stem cell transplants have been shown to reduce inflammation, promote motor neuron survival, and improve muscle strength.
As with other neurodegenerative diseases, the success of stem cell therapy in ALS will likely depend on a deeper understanding of disease mechanisms and finding the best ways to target and deliver treatment.
The Future of Stem Cell Therapy for Neurodegenerative Diseases
While stem cell therapy is not yet a viable cure for neurodegenerative diseases, Sivandzade et al. believe it represents one of the most promising paths forward. The ability to regenerate or repair damaged tissue offers hope where traditional therapies have fallen short. As research continues to advance, more clinical trials are likely to explore the safety and effectiveness of these treatments, along with better methods for personalizing therapies and improving the delivery of stem cells to targeted areas within the nervous system.
Source: Sivandzade F, Cucullo L. Regenerative Stem Cell Therapy for Neurodegenerative Diseases: An Overview. Int J Mol Sci. 2021 Feb 22;22(4):2153. doi: 10.3390/ijms22042153. PMID: 33671500; PMCID: PMC7926761.
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