Stem Cells for Parkinson's Disease Treatment

About Parkinson’s Disease

Parkinson’s disease results from the loss of dopaminergic neurons in the brain—cells responsible for coordinating muscle movement. Consequently, the disease not only compromises motor functions but also causes a range of non-motor symptoms. Over time, disease progresses worsening the symptoms.

Does Parkinson’s disease only affect older adults?

While Parkinson’s disease is most commonly diagnosed in individuals over the age of 60, it is not exclusive to the elderly. The risk of developing the disease increases with age, making older adults the predominant demographic. However, a small percentage of patients experience what is known as early-onset Parkinson’s disease, which can occur in younger individuals.

What do "on" and "off" periods mean in Parkinson’s disease?

The terms “on” and “off” refer to the fluctuations in motor control experienced by Parkinson’s disease patients in response to medication, particularly levodopa or other dopamine-enhancing drugs. On time describes periods when the medication is effective, and symptoms are well controlled. Off time refers to intervals when the medication’s effectiveness wears off, and symptoms return or worsen. This can occur before the next scheduled dose or due to long-term use of medication, which leads to a less predictable response over time.

I don’t have tremors. Can I still have Parkinson’s disease?

Yes, you can still be diagnosed with Parkinson’s disease even if you do not experience tremors. While tremors are one of the most recognized and common motor symptoms of Parkinson’s disease, they are not present in all patients. In fact, studies estimate that approximately 30% of individuals with Parkinson’s disease do not exhibit any tremor, especially during the early stages of the disease.

There is currently no cure for Parkinson’s disease among the conventional treatment options. Treatments primarily aim to alleviate symptoms by increasing dopamine levels. However, these therapies do not alter the disease's underlying mechanisms. As a result, researchers are shifting focus towards regenerative strategies, particularly Stem Cell Therapy, which has shown potential to restore lost neurons. Many clinical trials have demonstrated encouraging outcomes, prompting faster regulatory approvals.

Scientific research is also propelling stem cell therapy towards customized solutions, recognizing the variation in treatment responses based on patient’s characteristics and disease course, tailoring therapy accordingly has turned into a routine. Therefore, stem cell therapy is also venturing into personalized solutions to maximize its impact.

Diagnosis

Diagnosing Parkinson’s disease (PD) involves a combinatorial approach, as no single test can definitively confirm the condition. Due to the clinical overlap between Parkinson’s disease and other movement disorders, diagnostic procedures primarily focus on ruling out alternative conditions while supporting a diagnosis of Parkinson’s disease through a variety of assessments.

Physical Examination: This involves documenting the patient's medical history and evaluating their clinical symptoms. Typically, slowness of movement (bradykinesia) combined with at least one other motor symptom, such as rigidity or tremor, forms the basis for a conclusive diagnosis. Parkinson’s disease is one of the few neurological disorders where clinical symptoms alone can be sufficient for diagnosis.

Imaging: Techniques such as MRI, PET, and CT scans are not used to diagnose Parkinson’s disease directly but are instrumental in excluding other neurological conditions that present with similar symptoms.

Cognitive Examination: This assessment evaluates the patient's cognitive functions, which may deteriorate as the disease progresses. Cognitive decline is an important non-motor symptom often associated with later stages of the disease.

Blood Tests: While not specific to Parkinson’s disease, blood tests are used to eliminate other medical conditions that might mimic Parkinson symptoms.

Dopamine Transporter (DAT) Scan: Also referred to as single-photon emission computed tomography (SPECT), this scan helps differentiate Parkinson’s disease from other disorders by assessing dopamine activity in the brain. It is particularly useful in distinguishing Parkinson tremor from tremor in other conditions.

Dopamine Response Test: A hallmark indicator of Parkinson’s disease is a positive response to dopaminergic medications. Patients are administered medications used in Parkinson’s disease treatment, and if their symptoms show significant improvement, it strongly supports a diagnosis of Parkinson’s disease.

Genetic Testing: This is used to identify genetic mutations associated with Parkinson’s disease, such as SNCA, LRRK2, and PINK1. It is particularly recommended for patients with a family history of Parkinson’s disease or those diagnosed at a younger age. Genetic testing can also aid in predicting disease progression and determining eligibility for clinical trials.

Alpha-synuclein Test: Alpha-synuclein is a protein that forms clumps in the brains of individuals with Parkinson’s disease, leading to the loss of neurons. The presence of alpha-synuclein in cerebrospinal fluid can be indicative of Parkinson’s disease. However, this test is generally not required in routine clinical diagnosis.

With the increasing integration of Artificial Intelligence (AI) in healthcare, researchers are actively exploring the use of AI and Machine Learning (ML) algorithms for the early detection and accurate diagnosis of Parkinson’s disease. These technologies analyze complex patterns in imaging, movement data, and speech to identify the disease even in its initial stages, potentially revolutionizing diagnostic practices in the near future.

Early Signs & Symptoms of Parkinson’s Disease (PD)

The diagnosis of Parkinson’s disease (PD) relies heavily on its clinical manifestations, particularly the presence of motor and non-motor symptoms.

Tremor: Tremor at rest is a prominent but not essential symptom of the disease. If present, it usually manifests in one limb and is most noticeable when the limb is at rest. Tremor may disappear during voluntary movement and reappear during rest, a phenomenon known as re-emerging tremor, which is a common feature of Parkinson’s disease.

Bradykinesia/Slowed Movement: It is the key symptom of Parkinson’s disease. Patients take more time in performing simple tasks like standing up, walking, getting dressed, etc. Response to environmental stimuli is also delayed. In clinical settings, inability of rhythmic foot tapping, steady walking, or rapid tapping index finger and thumb indicates Parkinson’s disease.

Rigidity: It is also a common symptom. Patients appear stiff and have difficulty in moving muscles. For instance, patients struggle to stand from a chair, or show decreased arm swing while walking. It typically starts asymmetrically. Together with bradykinesia, muscle rigidity causes smaller handwriting with progressive reduction in letter size.

Gait Disturbance: Patients may walk with small, slow steps, are prone to frequent falls, and may display a tendency to walk or lean backward. Some compensate for balance loss by taking rapid, shuffling steps. A hallmark feature is freezing of gait, especially in response to external stimuli like passing people or a door.

In addition to the above defining motor symptoms, patients often experience a range of non-motor and secondary symptoms, including:

Pain: Muscle rigidity and abnormal posture frequently cause joint and muscle pain.

Muscle Contractions: The combination of reduced movement and rigidity can lead to painful cramps, especially in the legs and toes. Muscle contractions are a frequent complaint among patients.

Olfactory Impairment: A reduced or lost sense of smell is common and may appear in the early stages of the disease.

Orthostatic Hypotension: Patients may feel dizzy or even faint upon standing due to a sudden drop in blood pressure.

Non-motor Symptoms: They include constipation, loss of urinary retention, drilling, difficulty in swallowing, erectile dysfunction, hypotension, excessive limb movements during REM sleep etc.

Cognitive Decline: As the disease progresses, patients may experience a decline in cognitive functions, which can ultimately lead to dementia in the later stages.

Psychological Symptoms: Sleep disturbances, mood swings, depression, vivid dreams, hallucinations, and psychosis are common psychological issues faced by many individuals with Parkinson’s disease.

Available Types of Parkinson’s Disease

Parkinsonism is an umbrella term that includes Parkinson’s disease as well as other neurodegenerative disorders with similar symptoms. There are multiple types of Parkinsonism based on symptom patterns, causes, age of onset, and progression.

Idiopathic Parkinson’s Disease (Classic PD): This is the most common form of Parkinson’s disease, characterized primarily by bradykinesia, rigidity, and tremor. It occurs due to the degeneration of dopamine-producing (dopaminergic) nerve cells.

Genetic or Familial Parkinson’s Disease: This is a type of Parkinsonism disorder caused by inherited genetic mutations. It is more likely to affect younger individuals under 40. The symptom profile may be similar to idiopathic PD, but it may progress differently.

Atypical Parkinsonian Disorders: These are conditions that mimic Parkinson’s symptoms but are distinct in their progression and additional symptoms. They respond poorly to traditional Parkinson’s medications.

• Multiple System Atrophy (MSA): It occurs due to aggregates of alpha-synuclein and differs from Parkinson’s disease due to its relatively faster progression. In addition to common Parkinson’s symptoms, MSA also shows poor balance, slurred speech, abnormal eye movements, high-pitched sounds during breathing, etc. An MRI scan can distinguish between MSA and Parkinson’s disease.
• Progressive Supranuclear Palsy (PSP): It differs from Parkinson’s disease due to involvement of visual disorders (such as abnormal eye movements or blurred vision), symmetrical symptoms, and upright posture. Additionally, frequent falls and posture instability are more pronounced in PSP. MRI images, clinical symptoms, and rapid progression are its distinguishing features.
• Corticobasal Degeneration (CBD): The characteristic symptoms include difficulty with purposeful movements, involuntary limb movements, progressively declining language skills, and loss of sensory neurons.
• Dementia with Lewy Bodies (DLB): Similar to idiopathic PD but with early cognitive decline and hallucinations. Cognitive decline occurring before the motor symptoms suggests DLB instead of Parkinson’s disease.
• Secondary Parkinsonism: It is caused by external factors like drugs, toxins (e.g., MPTP), stroke or brain injury, infections, etc.

The above disorders should not be confused as different types of Parkinson’s disease.

Stages of Parkinson’s Disease

The progression of Parkinson’s disease is commonly described using the Hoehn and Yahr Scale, which outlines five stages based on the severity and spread of motor symptoms.

Stage 1: Symptoms affect only one side of the body (unilateral) with mild tremors, slight stiffness, or slower movements. No significant functional impairment is observed.

Stage 2: Symptoms affect both sides of the body (bilateral) with minimal balance issues.

Stage 3: Symptoms affect both sides of the body (bilateral) with mild disability. The patient can still function independently.

Stage 4: Patient has significant disability, but can still walk or stand.

Stage 5: Patients cannot live without assistance and are confined to bed or a wheelchair.

What Causes Parkinson’s Disease (PD)?

Parkinson’s disease (PD) occurs due to the abnormal accumulation of the alpha-synuclein protein within nerve cells, particularly in dopamine-producing neurons. These protein aggregates are known as Lewy bodies. The cells are unable to break down these clumps, which leads to neuronal damage and degeneration. Although the precise triggers that initiate alpha-synuclein deposition are not yet fully understood, ongoing research has identified several factors that may increase the risk of developing Parkinson’s disease.

Risk factors for Parkinson’s disease include:

Age: The risk of Parkinson’s disease increases significantly with age. Most cases begin after the age of 60. Although Parkinson’s disease can occur in younger individuals, it is considered rare. When diagnosed before the age of 50, it is referred to as early-onset Parkinson’s disease.

Genetics: Having one or more family members affected by Parkinson’s disease can elevate the risk, especially in early-onset cases. Mutations in specific genes, such as SNCA (which encodes alpha-synuclein), LRRK2, GBA, and PINK1, have been linked to Parkinson’s disease.

Gender: Men are statistically more likely to develop Parkinson’s disease than women. The reasons for this difference are not entirely clear but may involve hormonal and genetic factors.

Environment: Prolonged exposure to environmental toxins, such as herbicides and pesticides, has been associated with a slightly increased risk of Parkinson’s disease. These chemicals may contribute to oxidative stress and damage to dopamine neurons over time.

In addition to these factors, scientific studies suggest that biological processes such as chronic inflammation, oxidative stress caused by free radicals, and mitochondrial dysfunction may play crucial roles in the onset and progression of Parkinson’s disease. These mechanisms are actively being studied to identify potential therapeutic targets and better understand the disease’s complex pathology.

Stem Cells for Parkinson’s Disease (PD) Treatments

Parkinson’s disease (PD) treatment is primarily focused on controlling symptoms rather than addressing the root cause of the disease. Medications are designed to restore dopamine levels in the brain; however, their long-term use is often associated with adverse effects. Additionally, as the disease progresses, the effectiveness of these medications gradually diminishes. These limitations underscore the need for more advanced therapies that not only alleviate symptoms but also target the underlying disease pathology.

Stem cell therapy for Parkinson’s disease has emerged as a promising alternative due to its potential for neural regeneration. Unlike conventional treatments that simply elevate dopamine levels, stem cell therapy aims to restore the lost neurons, particularly dopaminergic cells. Extensive research, especially involving mesenchymal stem cells (MSCs), has focused on exploring the therapeutic potential of this approach in Parkinson’s disease. These studies have revealed several mechanisms by which stem cells may counteract disease progression:

• Stem cells promote the generation of new neurons from progenitor cells and safeguard existing dopaminergic neurons by releasing a range of neurotrophic growth factors, including BDNF, NGF, GDNF, FGF2, and VEGF. This supports neural regeneration, thereby slowing the advancement of the disease.
• Numerous scientific investigations have shown that stem cells have the ability to differentiate into dopaminergic neurons, contributing to neurological recovery in Parkinson’s disease patients.
• Stem cells also help to reduce neuroinflammation by decreasing the activation of brain immune cells and lowering the expression of pro-inflammatory markers such as TNFα, IL6, and iNOS mRNA. In parallel, MSCs enhance the production of anti-inflammatory cytokines such as TGFβ1, IL10, NO, HGF, IL4, and IDO.
• Moreover, MSCs modulate the immune system by inhibiting the activity of immune cells like T cells and natural killer (NK) cells, contributing to a more stable neurological environment.

Stem cell treatment for Parkinson's disease patients using MSC-based stem cell therapy has yielded promising results, suggesting its potential to modify the course of the disease and offer better control over both motor and non-motor symptoms. This therapeutic strategy not only opens new avenues for long-term disease management but also brings hope for achieving meaningful neurological restoration.

Frequently Asked Questions

Q1. Is Parkinson’s treatment with stem cells a curative treatment?

At present, stem cell therapy is not recognized as a definitive cure for Parkinson’s disease. However, it has shown significant therapeutic potential that extends beyond what current medications can offer. The improvements observed in clinical trials, including delayed disease progression, enhanced motor control, and neurological recovery, have led experts to classify stem cell therapy as a disease-modifying treatment rather than merely symptom-relieving. While it does not eliminate the disease entirely, Parkinson’s stem cell treatment targets the underlying causes, offering a promising strategy for altering the course of disease.

Q2. How is stem cell therapy better than the current treatment?

Conventional treatments for Parkinson’s disease focus solely on managing motor symptoms by temporarily increasing dopamine levels. These therapies do not stop disease progression or repair the damaged neurons, and their effectiveness wanes over time. In contrast, stem cell therapy offers a regenerative approach. It replenishes lost neurons, protects existing neurons, supports brain health, and reduces inflammation, all of which contribute to slowing disease progression. Unlike standard therapies, stem cell treatment aims to address the root cause of Parkinson’s, not just its outward symptoms.

Q3. What are the risks associated with stem cell therapy for Parkinson’s disease?

Despite concerns, stem cell therapy has not shown any major safety issues in the clinical trials conducted so far. In fact, numerous studies have demonstrated its safety profile, with no serious side effects or complications directly attributed to the therapy. However, it is important to note that large-scale, long-term clinical trials are still underway to fully evaluate the risks and efficacy over extended periods.

Q4. How soon can patients expect to see results from stem cell therapy?

Clinical trials involving stem cell therapy for Parkinson’s disease have reported observable improvements within a few weeks to a few months after treatment. Some patients have shown enhanced motor function, better gait stability, and improved quality of life within the first month of therapy. However, it is essential to understand that individual responses to stem cell treatment can vary significantly. Factors such as the stage of the disease, overall health, genetic background, and the specific type of stem cells used all influence the timeline and degree of improvement. As a result, while some patients may respond quickly, others may experience gradual or delayed effects.