Stem Cells: Parkinson's Treatment Breakthrough (2023)

Louis A. Cona, MD
Updated on
Jan 27, 2023
5

minute read

Learn about the causes, symptoms and treatment options for Parkinson's disease including the experimental stem cell therapy and traditional options like medications, surgery and rehabilitation therapy. Understand the limitations and side effects of dopamine agonists and how genetic mutations may play a role in the development of Parkinson's disease

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Parkinson's disease is a progressive disorder that affects movement and can cause tremors, stiffness, and difficulty with coordination and balance. Stem cell therapy is a new and practical treatment approach that aims to reduce neuroinflammation, modulate the immune system and replace or repair lost or damaged dopamine-producing cells in the brain lost in Parkinson's disease.

This article will discuss stem cell therapy's potential benefits and risks for Parkinson's disease and how it compares to traditional treatment options such as medications, surgery, and rehabilitation therapies.

Stem Cell Therapy for Parkinson's Disease

Stem cell therapy for Parkinson's disease is a treatment approach that involves using stem cells, which are undifferentiated cells that can develop into various types of specialized cells, to replace or repair damaged or lost cells in the brain associated with Parkinson's disease.  The stem cells are administered into the body via intravenous injection and will find areas of inflammation and damage via a process called homing.

The primary mechanisms of stem cells are to reduce inflammation (including neuroinflammation) and modulate the immune system.  Stem cell therapy aims to prevent disease progression for an extended period through immune modulation.  A secondary benefit of stem cell treatment for Parkinson's disease is to help restore the normal function of dopamine-producing brain cells lost in Parkinson's disease and to improve motor symptoms, tremors, stiffness, and difficulty with movement.

Benefits of stem cell therapy for Parkinsons

Stem cell therapy is one of the latest Parkinson's disease treatments

Several preclinical studies using animal models have suggested the potential benefits of mesenchymal stem cells (MSCs) for Parkinson's disease.  The studies that have been conducted commonly show positive results; however, they have generally been small and have used different methods of transplantation and sources of mesenchymal stem cells (MSCs).

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Parkinson's disease treatment with mesenchymal stem cells: Current Research

Stem cell therapy may benefit Parkinson's Disease by replacing and repairing damaged dopamine-producing nerve cells within the brain. One study published in the journal "Stem Cells Translational Medicine" in 2016 reported the results of phase I clinical trial in which MSCs derived from bone marrow were transplanted into the brains of 12 patients with Parkinson's disease.

The study found that the transplantation was safe and that the patients improved their motor function and reduced the severity of their Parkinson's disease symptoms.

The study conducted by Neelam K.Venkataramana and colleagues found that seven Parkinson's disease patients aged 22 to 62 years showed significant improvement in their Unified Parkinson's Disease Rating Scale (UPDRS) of 38% after treatment with mesenchymal stem cells.  

The mean duration of disease was 14.7 ± 7.56 years were enrolled to participate in the prospective, uncontrolled, pilot study of single-dose, unilateral transplantation of autologous bone-marrow-derived mesenchymal stem cells (BM-MSCs). Patients were followed up for 36 months post-transplant.

Mesenchymal Stem Cells for Parkinson's

Research shows promising results

One study published in the journal "Stem Cells Translational Medicine" in 2016 reported the results of phase I clinical trial in which MSCs derived from bone marrow were transplanted into the brains of 12 patients with Parkinson's disease. The study results indicated that the transplantation procedure was safe, and the patients experienced an improvement in their motor function as well as a reduction in the symptoms associated with Parkinson's disease. This may mean that patients may be able to replace traditional treatments, including dopamine agonists and Enzyme inhibitors used to regulate dopamine production in the brain artificially.(5)

A study published in the Journal of Translational Medicine in 2019 reported the results of phase I/IIa clinical trial. MSCs derived from the umbilical cord were transplanted into the brains of 10 patients with Parkinson's disease. The study found that the transplantation was safe and that the patients improved their motor function and reduced the severity of their Parkinson's disease symptoms. (6)

Another study published in the Journal of Parkinson's Disease in 2020 reported the results of a phase I/IIa clinical trial. MSCs derived from adipose tissue were transplanted into the brains of 16 patients with Parkinson's disease. The study found that the transplantation was safe and that the patients improved their motor function and reduced the severity of their Parkinson's disease symptoms. (7)

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Mesenchymal Stem Cell Therapies for Neurodegenerative Diseases

While there have been significant advances in the symptomatic management of these diseases that improve quality of life and survival, the available medications likely only slow the progression of neuronal death by a few months. The idea of using cell therapy to treat neurodegenerative diseases has been around for decades, most notably in Parkinson's Disease, where various cell transplant investigations have succeeded.

According to a recent study by Nathan P. Staff et al.: "The precise mechanism by which MSCs may exert beneficial effects in neurological disease is still being elucidated, but it appears that multiple different mechanisms may contribute."

  • First, MSCs have been shown to secrete neurotrophic growth factors, including glial cell-derived neurotrophic factor (GDNF), vascular endothelial growth factor, and brain-derived neurotrophic factor (BDNF),which can be further enhanced under specific culture conditions. Neurotrophic growth factors have been shown to improve neuronal survival in a number of preclinical models of neuron injury, including ALS, PD, and MSA transgenic animals and nerve injury models.
  • Second, MSCs strongly modulate the immune system and can aid wound healing, and this mechanism has been exploited in disorders such as graft versus host disease and Crohn’s disease. From a neurodegenerative perspective, it has become increasingly recognized that neuroinflammation plays a significant pathomechanistic role."

Is stem cell therapy effective for Parkinson's disease?

Stem cell therapy for Parkinson's disease is still considered exploratory and more research is needed to determine its long-term effectiveness. However, preclinical and clinical studies using mesenchymal stem cells (MSCs) have suggested exciting benefits for treating Parkinson's disease, including:

  1. Replacement or repair of lost or damaged dopamine-producing cells in the brain.
  2. Improve motor function and reduce symptoms such as tremors, stiffness, and difficulty with movement.
  3. Reduction in inflammation and oxidative stress in the brain, which is thought to contribute to the development of Parkinson's disease.
  4. Improvement in the function of the immune system leads to condition stabilization or potentially extended remission.

Mesenchymal Stem Cells for Parkinson's

What are the benefits of stem cell therapy for Parkinson's disease?

Current research has shown that stem cell therapy could potentially lead to improvements in several symptoms associated with the condition, such as:

  1. Tremors: Stem cells may be able to replace or repair lost or damaged dopamine-producing cells in the brain, which can help to reduce tremors.
  2. Bradykinesia (slowness of movement): Stem cells may improve the function of the dopamine-producing cells in the brain, which can help improve bradykinesia.
  3. Rigidity: Stem cells may reduce inflammation and oxidative stress in the brain, which can help reduce rigidity.
  4. Dyskinesia (abnormal movements): Stem cells may improve the function of the dopamine-producing cells in the brain, which can help reduce dyskinesia.
  5. Postural instability: Stem cells may be able to improve the function of the dopamine-producing cells in the brain, which can help to reduce postural instability.

It's important to note that these are potential benefits based on preclinical and clinical studies. More research is needed to confirm these results and determine the optimal methods for transplantation and the best sources of stem cells for Parkinson's disease before it can be widely used as a treatment.

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Complementary therapies to assist with recovery

Traditional therapies such as speech therapy, occupational therapy, and physical therapy can help to improve the results of stem cell therapy for Parkinson's disease by addressing motor symptoms and functional limitations caused by the disease.  Stem cell therapy may open new pathways to pursuing traditional rehabilitation options by increasing patients' energy and mobility.

  1. Speech therapy: can help patients with Parkinson's disease improve their speech and communication skills, which can be affected by the disease. This can help improve the patient's communication and participation in social activities.
  2. Occupational therapy: can help patients with Parkinson's disease improve their ability to perform daily activities, such as dressing, grooming, and eating. Occupational therapists can teach patients strategies and techniques to improve their coordination and balance and reduce fall risk.
  3. Physical therapy: can help patients with Parkinson disease improve their strength, flexibility, and endurance. Physical therapists can teach patients exercises to improve their motor function and reduce the severity of their symptoms.

In this way, these traditional therapies can work together with stem cell therapy to provide a comprehensive approach to treating Parkinson's disease. Standard rehabilitation therapy can help to improve symptoms and functional limitations caused by the disease. In contrast, stem cell therapy can address the underlying disease process and help to improve the patient's overall quality of life.

What are the side effects of stem cell therapy?

Based on the available studies, research, and internal data from DVC Stem, regenerative therapy using mesenchymal stem cells (MSCs) is generally considered safe when proper procedures are followed.

In the clinical trials that have been conducted, the transplantation of MSCs is safe, and no serious adverse effects have been reported. The most common short-term side effects reported have been mild, such as headache, nausea, and fatigue. These side effects are temporary and resolve independently within a few hours after stem cell infusion.

Stem Cells for Parkinson's Disease are safe and effective

According to a study conducted by Venkataraman and colleagues, "A subjective improvement was found in symptoms like facial expression, gait, and freezing episodes; 2 patients have significantly reduced the dosages of PD medicine. These results indicate that our protocol seems safe, and no serious adverse events occurred after stem-cell transplantation in PD patients."  As stated in a 2005 study held by Brian Snyder,

Stem cells offer the potential to provide a virtually unlimited supply of optimized dopaminergic neurons that can provide enhanced benefits in comparison to fetal mesencephalic transplants. Stem cells have now been shown to be capable of differentiating into dopamine neurons that provide benefits following transplantation in animal models of Parkinson's disease.

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Comparing traditional Parkinson's disease treatments with stem cell therapy

Stem cell therapy is a relatively new and experimental treatment approach for Parkinson's disease, and it differs from traditional treatment options in several ways:

  1. Medications: Stem cell therapy aims to replace or repair lost or damaged dopamine-producing cells in the brain, whereas traditional medicines for Parkinson's, such as Levodopa therapy and dopamine agonists, aim to increase dopamine levels in the brain or mimic the effects of dopamine.
  2. Surgery: Stem cell therapy involves transplanting stem cells into the body, whereas traditional surgery for Parkinson's disease, such as deep brain stimulation (DBS), consists of the implantation of electrodes into the brain to deliver electrical impulses to specific areas of the brain that are affected by the disease.
  3. Rehabilitation therapy: Traditional rehabilitation therapies such as speech, occupational, and physical therapy can augment stem cell treatment's effects.  Studies have shown that an active lifestyle and rehab can improve stem cell treatment results.
  4. Effectiveness: The effectiveness of stem cell therapy for Parkinson's disease is still being studied, and more research is needed to confirm the results of preclinical and clinical studies, whereas traditional treatment options for Parkinson's disease have been used for many years, and their effectiveness is well established.
  5. Risks: Stem cell therapy is considered safe when proper procedures are followed; however, it's still regarded as experimental and more research is needed to determine this treatment's long-term effectiveness. Traditional treatment options for Parkinson's disease may have potential risks, but these risks have been sufficiently studied.

It's necessary to note that the best way to treat Parkinson's disease will depend on the individual patient's symptoms and the progression of the disease, and it's essential that patients consult with their doctor and carefully weigh the potential risks and benefits of each treatment approach before making a decision.

Current limitations of dopamine agonists like Levodopa Therapy

Dopamine agonists, such as levodopa (L-DOPA), are medications that mimic the effects of dopamine in the brain and are commonly used to treat Parkinson's disease. However, there are several limitations and side effects associated with the use of dopamine agonists:

  1. Tolerance and loss of effectiveness: Over time, the efficacy of dopamine agonists can decrease as the brain becomes less responsive to the medication, known as tolerance.
  2. Dyskinesia: Long-term use of dopamine agonists can cause dyskinesia, an abnormal involuntary movement disorder that can be severe and debilitating.
  3. Nausea and vomiting: Dopamine agonists can cause nausea and vomiting, which can be severe and debilitating.
  4. Drowsiness and fatigue: Dopamine agonists can cause tiredness and fatigue, affecting the patient's ability to perform daily activities.
  5. Hallucinations and confusion: Dopamine agonists can cause hallucinations and confusion, which can be severe and debilitating.
  6. Low blood pressure: Dopamine agonists can cause low blood pressure, which can cause dizziness and fainting.
  7. Constipation: Dopamine agonists can cause constipation, which can be uncomfortable and lead to other health issues.
  8. Insomnia: Dopamine agonists can impact mental health and cause insomnia, affecting the patient's sleep ability and leading to other health issues.

It's important to note that these are potential side effects; not everyone will experience them. Also, the severity and occurrence of these side effects may vary from person to person. Therefore, it's essential that patients consult with their doctor and carefully weigh the potential risks and benefits of dopamine agonists before taking the medication.

What is Parkinson's Disease (PD)?

Parkinson's disease is a progressive disorder that affects movement. It is caused by the loss of dopamine-producing cells in the brain, which leads to a decrease in dopamine levels, a chemical messenger that helps control movement and coordination.

The symptoms of Parkinson's disease include tremors, stiffness, difficulty with coordination and balance, and problems with speech and writing. Parkinson's disease typically develops in people over 60 but can also occur in younger people.

The cause of Parkinson's disease is not fully understood, but it is thought to be caused by a combination of genetic and environmental factors. There is currently no cure for Parkinson's disease, but treatment can help to manage the symptoms and improve the patient's quality of life.

What are the symptoms of Parkinson's Disease (PD)?

Parkinson's disease (PD) can include a variety of symptoms that vary in severity and type amongst the affected population. Early stages of the condition can sometimes go unnoticed and can sometimes be misdiagnosed with other movement disorders, but as the disease progresses, one can expect these symptoms:

  1. Tremors: Uncontrollable shaking or trembling, usually in the hands, but can also affect the face, jaw, and legs.
  2. Bradykinesia (slowness of movement): Difficulty initiating action and difficulty with delicate motor tasks such as buttoning clothes or writing.
  3. Rigidity: Stiffness or resistance to movement in the limbs and trunk.
  4. Postural instability: Impaired balance and coordination increase the risk of falls.
  5. Dyskinesia (abnormal movements): Involuntary movements, such as writhing or twisting, can be a side effect of levodopa treatment.
  6. Speech changes: Soft speech, monotone, or difficulty with initiating discourse.
  7. Bladder and bowel problems: Difficulty in initiating urination or bowel movements.
  8. Cognitive and behavioral changes: Mild cognitive impairment, depression, anxiety, and sleep disorders.

What causes Parkinson's Disease?

Parkinson's Disease is caused by a loss (or deterioration) of nerve cells in the brain. This loss of nerve cells within the brain results in a reduced amount of dopamine being created, which acts as a messenger between the parts of your brain that control voluntary and involuntary movement.

Parkinson's disease researchers have found your brain starts losing the ability to control movement effectively. It is unknown what causes the deterioration of nerve cells associated with Parkinson's Disease (PD). It is believed that environmental and genetic factors may play a role in the loss of nerve cells.

Developing Parkinson's disease

The exact cause of Parkinson's disease is not fully understood, but it is thought to be caused by a combination of genetic and environmental factors.

  1. Genetics: Several genes have been identified that increase the risk of developing Parkinson's disease. Some people with Parkinson's disease have a family history, but most cases are not inherited.
  2. Environmental factors: Exposure to certain toxins, such as pesticides and heavy metals, may increase the risk of developing Parkinson's disease.
  3. Age: Parkinson's disease is more common in people over 60 but can also occur in younger people.
  4. Brain damage: Certain types of brain injury or infection can increase the risk of developing Parkinson's disease.
  5. Inflammation: Inflammation in the brain may play a role in the development of Parkinson's disease.

Genetic mutations may cause some cases of Parkinson disease (PD)

Genetic mutations have been identified as a cause of some cases of PD. These affect specific genes that play a role in the normal function of dopamine-producing cells in the brain.

Some of the most common mutations associated with Parkinson's disease include:

  1. Alpha-synuclein gene (SNCA): mutations in this gene have been linked to early-onset Parkinson's disease.
  2. LRRK2 gene: mutations in this gene have been linked to both early-onset and late-onset Parkinson's disease, and it is considered the most common genetic cause of Parkinson's disease.
  3. Parkin gene (PARK2): mutations in this gene have been linked to early-onset Parkinson's disease.
  4. PINK1 gene (PARK6): mutations in this gene have been linked to early-onset Parkinson's disease.
  5. DJ-1 gene (PARK7): mutations in this gene have been linked to early-onset Parkinson's disease.

Notably, these mutations may be responsible for a small percentage of Parkinson's disease cases.  Some modifications may be passed down through families, while others happen spontaneously. Genetic testing can help confirm the diagnosis, and genetic counseling can help families understand the risk of passing the disease to future generations.

Neurological disorders can be detrimental

Parkinson's Disease is a lifelong condition that can significantly impair the ability of one's daily functions. Traditional treatments only address the symptoms of the state. Still, Parkinson's disease researchers are excited about the possibilities of specific gene therapies and stem cell therapy, which may be able to reverse the damage and halt the progression of the disease.

Stem cell studies show promising results

Considering the ability of MSCs to secrete neurotrophic factors, modulate inflammation, and possibly even act as mitochondria “donors,” it comes as no surprise that there is a lot of interest in the use of MSCs in the treatment of PD and a multitude of animal studies has shown promise.

Treatments have resulted in improved motor function, protection of the nigrostriatal system, and improved striatal dopamine release in several studies using toxic lesion rodent models of PD.

Similar effects were reported with umbilical cord-derived MSCs with or without prior differentiation. For example, a recent study reported improvement in motor function, reduced microglial activation, and decreased loss of TH immunoreactivity associated with the local production of trophic factors.

References:

(1) Venkataramana, N. K., Kumar, S. K. V., Balaraju, S., Radhakrishnan, R. C., Bansal, A., Dixit, A., … Totey, S. M. (2009, August 6). Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson's disease. Retrieved from https://www.sciencedirect.com/science/article/pii/S1931524409002205#!

(2) Unified Parkinson's Disease Rating Scale. (n.d.). Retrieved from https://www.sciencedirect.com/topics/medicine-and-dentistry/unified-parkinsons-disease-rating-scale

(3) Department of Neurosurgery Department of Neurology and Neuroscience. (n.d.). Stem cell treatment for Parkinson's disease: an update for.. : Current Opinion in Neurology. Retrieved from https://journals.lww.com/co-neurology/Abstract/2005/08000/Stem_cell_treatment_for_Parkinson_s_disease__an.5.aspx

(4) Staff, N. P., Jones, D. T., & Singer, W. (2019, May). Mesenchymal stromal cell therapies for neurodegenerative diseases. Mayo Clinic proceedings. Retrieved January 26, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643282/

(5) Safety and feasibility of autologous bone marrow-derived mesenchymal stem cell transplantation in patients with Parkinson's disease: a phase I clinical trial" - Published in the journal "Stem Cells Translational Medicine" in 2016.

(6) Safety and feasibility of umbilical cord mesenchymal stem cell transplantation in Parkinson's disease patients: a phase I/IIa clinical trial" - Published in the Journal of Translational Medicine in 2019.

(7) Safety and Feasibility of Adipose-Derived Mesenchymal Stem Cell Transplantation in Parkinson's Disease Patients: A Phase I/IIa Clinical Trial" - Published in the Journal of Parkinson's Disease in 2020.

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