Parkinson’s Disease Causes and the Search for Better Answers

Parkinson’s involves loss of dopamine-producing neurons. The decreased dopamine signalling compromises movement coordination. The disease is recognised by symptoms like tremors or slowed movement.  

The question arises: Why are the neurons subjected to vulnerability in the first place?

Various factors like genetics, mitochondrial dysfunction, neuroinflammation, elevated oxidative stress or environmental factors contribute to Parkinson’s development. However, the complexity of the disease reflects the complexity of its development. Researchers highlight that there is no single cause of Parkinson’s disease. Current therapies combat symptoms and improve the quality of life of the patients, but they do not target the underlying cause. The emergence of regenerative medicine in the form of stem cell therapy has raised hope for neuronal restoration. The current article reflects Parkinson’s disease causes, symptoms, and treatment approach, including stem cell therapy. 

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What Causes Parkinson’s Disease?

Parkinson’s occurs when the brain cells die off gradually. The drop in dopamine levels sends signals to the brain, resulting in symptoms like tremors, stiffness or slowed movements. The core risk factors include: 

• Age: Affects individuals >60 years; for many individuals Pakinson’s appears as early onset
• Gender: Males are more susceptible 
• Hereditary: Family history of an individual with Parkinson’s
• Environmental Exposure: Long-term exposure to pesticides, metallic pollutants like manganese, etc. 

There cannot be a single Parkinson’s Disease Causes marked for its occurrence. Various complications associated with disease progression include:

• Autonomic Nervous System: Appearance of co-morbid health conditions like hypertension, digestion, sweating, loss of bladder control
• Cognitive Issues: Trouble with focus, memory or decision-making ability
• Injury: Increased risk of falls due to disorientation
• Loss of Independence: Compromised cognition or increased risk of fall increases dependency in performing daily life activities
• Breathing or Swallowing: Trouble with swallowing, breathing difficulties, increased risk of food choking
• Mental Health: Changes in the brain, loss of dopamine neurons, etc. affect one’s mood or emotional health

What are the Noticeable Signs and Symptoms? 

Parkinson’s Disease Symptoms Appear Distinct for Everyone. Common Symptoms Include:

• Tremor: Rhythmic shaking of hands, fingers, foot or jaws
• Slowed Movement (Bradykinesia): Difficulty in even performing daily life tasks
• Stiffness: Muscle spasm, muscle feels tense and painful. The movement gets jerky
• Poor Posture and Balance: Stooped posture, prone to imbalance and falls
• Loss of Automatic Movement: Difficulty in certain movements like blinking, swinging, smiling
• Speech Change: Slurred speech, monotone, hesitation
• Nonmotor Symptoms: Depression, anxiety, insomnia, constipation, loss of bladder control

How Is Parkinson’s Disease Diagnosed?

• Take note of patient’s medical history
• Blood and urine tests to determine biological parameters
• Imaging including CT scan, MRI, brain ultrasound or PET
• Alpha-synuclein test for disease detection at an early stage or even before the symptoms appear

*NOTE: The correct treatment approach depends on adequate Parkinson’s disease causes identification and complication.

Current Parkinson’s Disease Treatment Regime

Medication

• Combats physical or psychological symptoms like tremors, walking difficulties, movement
• Carbidopa-levodopa is a common medication; levodopa passes to the brain and becomes dopamine; together, this medicine prevents nausea
• Dopamine agonists like pramipexole, rotigotine, apomorphine, etc. These medications mimic dopamine effects in the brain
• Monoamine oxidase B (MAO B) inhibitors like selegiline, safinamide, rasagiline block the enzyme that is responsible for dopamine breakdown
• COMT inhibitors like entacapone, opicapone, and tolcapone prevent dopamine breakdown
• Other medications include pimavanserin, an A2A receptor antagonist, amantadine, anticholinergics, etc.
• However, the medications have serious side effects including nausea, confusion, hallucinations, urinary incontinence, blurred vision, etc. 

Deep Brain Stimulation

• Surgical procedure involves insertion of an electrode into the brain
• Electrode is connected with a pacemaker placed in the chest
• The procedure sends electrical signals to the brain that controls Parkinson’s symptoms
• Improves tremor, controls involuntary muscle movement (dyskinesia)
• Associated with certain side effects like bleeding, injury, skin breakage, infection, muscular twitching, speech or vision problems

Advanced Treatment

• MRI-guided ultrasound, MRgFUS 
• Minimally invasive, manages tremor
• Ultrasound waves at a very high temperature burn the area that creates tremors
• Certain side effects, including walking or speech issues, dyskinesia

Why are Researchers Looking Beyond Conventional Treatment?

The conventional Parkinson’s disease treatment focuses on symptom management. However, none address the actual issue, that is, neuronal loss. The emerging regenerative medicine challenges these conventional concepts. Parkinson’s Stem Cell Treatment focuses on neuronal regeneration and protects the existing neurons. They significantly slow down disease progression, combat neural inflammation, and modulate immune response. Researchers are actively using mesenchymal stem cells (MSCs) for their ability to regenerate into distinct cell types and paracrine signalling. Various sources for MSCs isolation include umbilical cord blood/tissue, adipose tissue or bone marrow.   

Parkinson’s Stem Cell Treatment: What Does the Science Say?

Stem cells look promising in replacing lost dopamine-producing neurons. The intent is to prevent further neuronal loss and create a supportive microenvironment for survival of the existing neurons. Scientific studies reflect the working mechanism of the stem cells as:

Brain Repair

• MSCs release various signaling molecules, growth factors, and cytokines
• Regeneration of the naive dopamine-producing neuron and replacement of the damaged one

Immunomodulation

• Promotes release of anti-inflammatory molecules (decreases IL-10, TGF-β)
• Suppresses pro-inflammatory signal effects (TNFα, IL-1β, IL-6)
• Alters microglia and macrophages into reparative phenotypes

Neurotrophic Support

• Releases various growth factors like BDNF, GDNF, VEGF, FGF, etc.
• Supports synaptic plasticity and survival of dopamine-producing neurons
• Decreases neurodegeneration and displays symptomatic improvement

Antioxidant and Anti-Apoptotic Effects

• Increases antioxidants like SOD and catalase, and counteracts free radical effects
• Improves mitochondrial function and reduces neuronal apoptosis
• Decreases caspase-3 activation, protects dopaminergic neurons [1]

Exosomal Signalling

• Stem cells release tiny extracellular vesicles called exosomes
• Increased delivery of microRNAs (miR21, miR133b)
• Decreases αsynuclein pathology [2]

Stem Cell Treatment for Parkinson’s in India: Where Does It Stand?

Currently, Parkinson’s Stem Cell Treatment in India has gained considerable attention. The evolving research and collaboration with clinicians have turned the focus to investigating stem cells’ role in replacing and restoring neurons. Stem cell Treatment for Parkinson’s in India is ongoing research rather than being considered as a standalone treatment. Clinicians are considering the introduction of stem cells as a supportive action to gain improved treatment outcomes. 

Besides, availability of developed infrastructure, experienced clinicians, and complete support for treatment and rehabilitation makes India a popular choice for medical tourism. 

Patients and their Family Members Considering the Treatment Must Consider:

• Quality, source, and isolation procedure of the stem cells
• Evidence-based information related to the approach
• Procedure if part of the clinical trial
• Consult experienced clinicians and renowned clinics, discuss the procedure in details
• Don’t fall for the false hope that stem cells are the miracle treatment, because they are not
• Setting realistic goals is a crucial aspect when considering stem cell treatment for parkinson’s in India
• The goal must be to determine the meaningfulness, durability, safety and neurological benefits 
• The outcome of the Parkinson’s stem cell treatment varies among patients. It depends on cell type, administration procedure, disease severity, and the individual’s response

*Advancells, India is a leading clinical-grade stem cell supplier for various neurological conditions including Parkinson’s. The cells are isolated and maintained with utmost care. The product undergoes stringent quality control to determine cell viability, purity, morphology, microbial load testing, and functional activity before it is dispatched.

Conclusion

Parkinson’s disease causes mainly involves dopaminergic neuronal loss. The emergence of regenerative medicine in the form of stem cell treatment has raised new hope related to the management of underlying conditions. Currently, stem cell therapy is still evolving. In the future, large-scale clinical trials can establish long-term efficacy and safety of the treatment. 

References

1. Park JM, Rahmati M, Lee SC, Shin JI, Kim YW. Effects of mesenchymal stem cell on dopaminergic neurons, motor and memory functions in animal models of Parkinson’s disease: a systematic review and meta-analysis. Neural Regeneration Research. 2023 Nov 8;19(7):1584. 
2. Wang CC, Hu XM, Long YF, Huang HR, He Y, Xu ZR, Qi ZQ. Treatment of Parkinson’s disease model with human umbilical cord mesenchymal stem cell-derived exosomes loaded with BDNF. Life sciences. 2024 Nov 1;356:123014. 

FAQ’s

Q- Is Parkinson’s Curable?

Parkinson’s isn’t curable; there is progressive loss of neurons. Many treatments, including medication, surgery and regenerative medicine, help in symptom management and slow down disease progression.

Q- Is Parkinson’s Stem Cell Treatment Available in India?

Yes, stem cell treatment for parkinson’s in India is available. 

Q- Who Can Consider Stem Cell-Based Clinical Trials?

Patients unresponsive to conventional treatment can consider. Participants at an early to moderate disease state and with other co-morbid conditions like certain blood cancers, metabolic disorders, etc can also be considered.

Q- Can Stem Cells Replace Lost Dopamine-Producing Neurons?

Yes, early research evidence shows stem cells’ ability to replace lost dopamine-producing neurons.