Parkinson’s disease or “PD” is a neurodegenerative disorder of the central nervous system. PD is predominantly diagnosed in elderly patients, but 5% of cases happen to patients less than 40 years old. Parkinson’s disease affects more than 6.1 million people worldwide, and patients diagnosed with primary parkinsonism can be characterized by non-motor and motor symptoms.
The disruptions caused in motor control often include:
- Mild Tremors ( Typically when over 65% of dopamine neurons have degenerated in the substantia nigra.
- Slowness in movement ( bradykinesia )
- Muscle rigidity
- Poor Posture or Postural instability
History of Parkinsons Disease & Paralysis Agitans
In 1817, a British physician named James Parkinson described in his treatise “An Essay on the Shaking Palsy” the main symptoms of the disease, which was later named after him. Other names and classifications in the Parkinson’s disease family include:
- Shaking Palsy
- Idiopathic Parkinsonism
- Parkinson’s syndrome
- Corticobasal Degeneration (CBD)
- Drug-induced Parkinsonism
- Vascular (Arteriosclerotic) parkinsonism or Multi-infarct parkinsonism
- Progressive supranuclear palsy (PSP)
- Hypokinetic–rigid syndrome (HRS)
- Essential Tremor (ET)
- Paralysis Agitans
What Causes Parkinson’s Disease
For most patients (Over 85% of cases), the diagnosis of Parkinson’s disease is idiopathic or of unknown origin. Researchers studying Parkinson’s believe that it may be caused by several factors ranging from systemic autoimmune diseases, genetic/familial to environmental causes. Familial Parkinson’s is quite rare, and less than 15% of our patients have reported a family history of Neurodegenerative disorders such as ALS, Ischemic Strokes, or Ataxia. The primary pathophysiology of Parkinson’s disease is the death of dopaminergic neurons (dopamine-creating cells) and motoneurons in the midbrain (substantia nigra region.) The usual symptoms that are associated with PD occur due to the loss of paracrine cell signaling capacity of neurotransmitters, especially dopamine. Some other potential risk factors for neurodegenerative diseases like MND and PD include oxidative pressures, autoimmune system complication from disorders such as lupus, hereditary variables, environmental factors, neuroleptics or calcium antagonists, intoxication (Drug-induced parkinsonism) or traumatic brain injuries. 
Signs & Symptoms of Parkinson’s Disease
A diagnosis of PD is given when a patient develops a rapid accumulation of the alpha-synuclein proteins into the “Lewy bodies” due to the inadequate activity of neurons and dopamine. Dementia with Lewy bodies is reported as the 3rd leading cause after Alzheimer’s and Vascular Dementia. The four main symptoms of Parkinson’s disease are bradykinesia, rigors, tremors, and postural instability.
Bradykinesia – Bradykinesis
Bradykinesia means that patient moves slower and less able to change positions. Activities like getting up, walking, turning can difficult. Sometimes for patients in late-stage Parkinson’s voluntary movement is almost impossible due to akinesia.
The first sign of PD disease may be that an arm resonates less when walking. The patients’ posture is often bent due to frontal gait disorder. A turn may require many intermediate steps. Gestures and facial expressions decrease; the face of a patient often looks emotionless like a mask. The voice becomes quieter and more monotonous, and language skills become more indistinct. The person has difficulty eating, often choking. The handwriting becomes small and illegible.
Rigor describes the stiffness of the muscles. Every movement seems to be against fierce resistance. Often, the neck and shoulder muscles are affected, often one-sided. A neurologist may be able to detect the Cogwheel phenomenon. An example of cogwheel rigidity can be seen when the doctor attempts to stretch the angled arm of a patient with Parkinson’s, which results in a reaction of jerky movements as if a cogwheel were moving.
Resting tremors or trembling often occurs in patients with Parkinson’s usually on one-side. The slow tremors of the hands, and later the feet occur mostly at periods of rest. The resting tremors often disappear during exercise or sleep. The tremor is not present in all cases, but many patients report empty hands, fingers rubbing against each other in a movement similar to that of “counting coins.”
Postural instability is one of the primary motor symptom seen in a later stage of shaking palsy. The lack of balance is especially apparent when the patient is standing upright. PD directly affects the reflexes that help us balance, and patients with postural instability can easily fall with the slightest touch. This symptom is very dangerous for patients and often leads to severe falls resulting in orthopedic injuries to the hips, knees, shoulders, and arms.
Complications of PD: Akinetic Crisis
An akinetic crisis (AC) or acute akinesia is a life-threatening complication of PD that can be caused by a variety of issues including infections, medication errors, or failed surgery. A patient with AC becomes completely immobile, can no longer speak and no longer swallow. Accompanying symptoms include sweating and fast pulse. Such a crisis is dangerous and must be treated immediately. Without the ability to swallow, saliva can enter the lungs and cause pneumonia.
Early Onset Parkinson’s
When someone aged between 18-50 years old receives a clinical diagnosis of Parkinson’s, it is called young onset Parkinson’s disease or early-onset Parkinson’s disease. The symptoms of PD are usually the same regardless of age, but younger patients have very different experiences with the condition due to their age. From a psychological, social, and medical standpoint, managing PD is particularly difficult for younger patients and their families.
Early symptoms and concomitant symptoms for Onset of Parkinson’s disease include:
- The sense of smell worsens
- Sleep disorders associated with involuntary and violent movements during REM sleep – (REMS sleep behavior disorder)
- Frequent Depression and unhappy moods
- Diffuse muscle and joint pains in the shoulder-arm areas (due to muscle stiffness and limited mobility)
- Extremely oily skin due to hyperactive sebaceous glands in the face
- Issues with body temperature and circulatory system regulation
- Problems with proper bladder and bowel function
- Reduced Cognition
5 Stages of Parkinson’s Disease
Symptoms of Parkinson’s vary person to person and can take a while to manifest, and the disease is regarded as slow moving or “insidious onset.” Early symptoms include Neuropathy and tremors with clumsy motions even when the limbs are at rest. Severe symptoms include muscle rigidity, bradykinesia, and gait disorders. Other non-motor symptoms include incontinent urine, depression, insomnia, and astriction. Neurologists have established the Hoehn and Yahr Scale, which consists of the five stages of PD to help classify patients in clinical trials and research studies around the world.
Diagnosis of Parkinsonian Syndromes
Diagnosis can be challenging, but patients we have treated at the regeneration center for PD generally don’t show significant abnormalities in lab panels or blood tests, but trained neurologists can usually notice irregularities in Cerebrospinal fluid biomarkers and through the use of radiography tools such as brain MRI or CT Scan.
The symptoms of Parkinson’s are progressive, but each patient shows a different rate of progression. Losing Motion function causes a decline in the overall quality of life, and drugs have shown minimal effects in clinical trials and treatments around the world. For severe cases, traditional medicine has virtually no effect and can make it even more difficult to control the symptoms due to new side effects. Severe patients often demonstrate catalepsy and can develop other complications, such as lung respiratory failure, Parkinson’s disease psychosis, and Parkinson’s related hallucinations.
Pharmaceutical-based solutions have shown to be ineffective for symptomatic patients and cannot alter the course of the degenerative disorder. Drug-based treatments cannot raise the number of neuron cells, thus making most of the traditional treatment options ineffective.
Genetic Testing for Parkinson’s
Hereditary neurodegenerative diseases occur when genetic mutations are passed from the parents to their children. A genetic disease, however, can be due to environmental causes or hereditary. Random mutations can cause some genetic conditions in the DNA due to environmental factors or exposure to toxins. Familial (hereditary) PD accounts for less than 15% of all confirmed cases. Inherited parkinsonism is either an X-linked dominant pattern or autosomal recessive pattern. Each parent carries one copy of the mutated gene, but often do not show any signs or symptoms of the condition. For this reason, autosomal recessive PD can often be misdiagnosed dementia with Lewy bodies, multiple system atrophy (MSA) or ALS/MND. The most common genetic markers used for screening hereditary Parkinsons include LRRK2, Glucocerebrosidase (GBA), RIC3, PARK2, PARK6, PARK7, SYNJ1, PTRHD1, TMEM230, UCHL1, DNAJC6, CYP2D6, VPS13C, PODXL, DNAJC13, CHCHD2, and RAB39B. Recent research also suggests that abnormalities in tau proteins are also a potential cause of familial parkinsonism and frontotemporal dementia.
The Regeneration center offers gene sequencing tests for 18 of the most common genes causes associated with Parkinson’s disease and monogenic parkinsonism related conditions. The genes we can test for include: SLC6A3, LRRK2, DNAJC6, FBXO7, GCH1, PARK7, VPS35, PINK1, PRKRA, PRKN, SNCA, SPR, TH, CHCHD2, MAPT, ATP13A2, ATP7B & DCTN1
Please note we do not offer gene therapy for Parkinson’s disease but offer the gene testing services for existing patients looking to confirm a diagnosis or who are displaying classical signs of parkinsonism can benefit from molecular diagnostic testing. The panels offered by the Regen Center covers genes with recessive, dominant and X-linked inheritance patterns which are useful in clarifying the risk of recurrence and in helping to determine which relatives might be at risk based on the family history.
TREATMENT PRECAUTIONS & RISKSUsing stem cells for Parkinson’s is not appropriate in all cases. Patients with unidentifiable brain damage, travel restrictions, or severe neural atrophy will not be good candidates for treatment.
Treatment Options for Patients With Parkinson’s
Parkinson’s disease and some of the symptoms are treatable but parkinson’s cure using gene therapy is not available. Recent developments in gene editing and exosome therapy do offer hope for a potential cure for Parkinson, but the research is still in its infancy and not proven to be consistent. Traditional therapies for PD consists of several components to counter low levels of dopamine neurotransmitter in the brain with the most common one being pharmaceutical medications. Anti-Parkinson medications are effective for some patients allowing the disease to be under control for many years. Over time, however, the effect of new Parkinson drugs may decrease. Therefore, frequent adjustments of the medications are necessary at certain intervals to ensure the treatments remain effective.
The most common medications for Parkinson’s Disease include:
- Levodopa (L-Dopa) – Levodopa medication is a precursor of dopamine and assists nerve cells in absorbing the medication and converting into dopamine. L-Dopa has positive effects on mobility, against muscle stiffness, but also tremors. However, after a long period of L-Dopa therapy results become to cause a variety of side effects, including hyperkinesia (unpredictable and uncontrollable movements) and on-off phenomena. To counteract fluctuating levels of efficacy in advanced stages of shaking palsy, some patients have a dopamine pump installed internally that to delivers the dopamine continuously via an implanted probe into the small intestine or under the skin.
- Carbidopa-levodopa (Sinemet) – This new medication is a combination of carbidopa and levodopa. This more modern medication can prevent the destruction of levodopa in the digestive tract and can also help reduces some undesired side effects such as nausea.
- Dopamine Agonists – This group of PD medications mimics the effects of dopamine on the brain causing neuron cells to react to them exactly as they would to natural dopamine. These medications also increase the effect of the existing dopamine (pramipexole, lisuride, ropinirole). Newer forms of dopamine agonists ensure consistent even drug levels throughout the day and must be taken in part only once a day (extended-release ropinirole, extended-release pramipexole). These medications can also deliver the active ingredient via a dermal patch, which must be changed daily (DescriptionRotigotine patch). Side effects of dopamine agonists may occur in the form of daytime fatigue or drowsiness, and the form of compulsive behavior such as compulsive purchasing and gambling addictions.
- There are also other groups of medications that can help reduce the effects of dopamine (COMT inhibitors such as entacapone and tolcapone) or slow down its breakdown (MAO-B inhibitors such as selegiline and rasagiline).
- Anticholinergics (Biperiden, Bornaprin) can effectively reduce the tremors
- NMDA inhibitors amantadine can help to increase dopamine release and improve mobility for some patients
Some doctors also recommend using different groups of active ingredients with each other, but this approach is very challenging because the symptoms and side effects of each medication can be very different lead to an unexpected response to the combined medications.
Deep Brain Stimulation (DBS) & Surgical Interventions for PD
For some patients with Parkinson’s that do not respond well to medication, they may be offered brain surgery as a treatment option. There are very few surgical options for treating conditions like MS & PD, but the most common one is called deep brain stimulation (DBS). DBS involves surgically implanting a device in the brain that generates electrical impulses via a battery-operated neurostimulator. The results of DBS are not very effective over the long term and carry a lot of risk due to the need for performing surgery on a patient who is already sick. Due to this risk, doctors and patients must weigh the potential risk with benefits and programmed pacemakers in the Brain should only be used in cases when drug therapy is no longer useful.
Stem Cell Treatment for Parkinson’s
In Parkinson’s disease, specific nerve cells die in the brain. Doctors worldwide are therefore to find a way to replace these dead neural stem cells with new functional cells and neurotransmitters. One idea was to take stem cells from the bone marrow and implant them in the brain (stem cell injection, stem cell transplantation). According to the theory, the stem cells in the mind of the patient
should convert into new, functional nerve cells, or at least compensate for deficits. This approach sounded promising, but transplantation of bone marrow stem cells did not always lead to the results wanted or ineffective and have potential harm to the patient. Since the development of adult stem cell therapy has discovered new methods to try to replicate/replace diseased cells using isolated and expanded mesenchymal cells ( MSC+). Expanded Neural stem cells have a high rate of proliferative activity, especially in the cortex of the brain. The cells used in the treatment are first isolated from areas where neurogenesis occurs. The multipotent stem cells require culturing (expansion) over several days to differentiate them into astrocytes, neurons, and oligodendrocytes. The Regeneration Center offers a promising new protocol to treat Parkinson’s using neural stem cells replacement therapy effectively. The Regeneration Center MSC+ Ncell treatment is unique as it targets the central nervous system to enhance motor neuron function. The therapy also focuses on the underlying mental symptoms via fresh infusion of progenitor cells that can release dopa, which then raises the levels of new neuron cells that are needed to slow down, stop or in some cases reverse the gradual progression of Parkinson’s before its too late.
Stem Cell Therapy for Memory Loss
The Regen Center Ncell therapy allows us targeted and customizable cell delivery to help induce neurogenesis over several stages, depending on the severity of the patients underlying health. The treatments are effective in being absorbed by the tissues after crossing the brain barrier through the use of cerebrospinal fluid or nebulizer.
Treatments options for PD using Stem cells may include:
- Radio Guided Therapy
- The stereotactic technique of deep brain stimulation
- Striatum stereotactic pallidotomy
- Subarachnoid stem cell implantation via lumbar puncture
- Brain stereotactic operation
Implanted neural stem cells help dopamine transport channels and eventually differentiate into dopaminergic neuron cells to continue as healthy & functional neurotransmitters. Mesenchymal stem cells that we use for treatment MSC+ Mesenchymal cells that are differentiated into nerve cells, including dopamine-producing cells. The quantity & types of implanted cells (growth factors) dependent strictly on the patient’s medical needs.
Physiotherapy Management for Patients with Parkinsons Disease
Physical therapy cannot reverse or stop Parkinson’s disease, but it can help improve a patients independence and overall quality of life by helping to improve cardiovascular health, strength, movement range, and relieving pain. Good physiotherapeutic care is essential to maintain mobility as long as possible. Speech therapy can also help patients when the language and swallowing capacity get impaired. Non-verbal communication via gestures and facial expressions should also be encouraged whenever possible.
For families and caretakers, occupational therapy and psychological care also help patients cope independently with everyday life or carry out hobbies as they would typically have. A professional therapist can help sufferers and families deal with the mental health problems or symptoms the patient might be experiencing.
Foods to Eat and Avoid
While there is no single Parkinson specific diet to maintain good health most patients with PD should be more cautious than most by eliminating junk food and trying to maintain a balanced diet full of antioxidants (vegetables, fruits & dark chocolate), whole grains, dairy fat and protein-rich foods such as legumes and meat. Lifestyle diets such as the Mediterranean dietand ketogenic diet do have potential to positively influence both motor and nonmotor symptoms of patients with Parkinson’s.
Guidelines for treatment of PD
The goal of the therapy for Parkinson’s is to alleviate the patients’ symptoms and restore any lost neurological function. The treatment process is performed on an out-patient, and transplanting cells is done in a non-invasive way. Stem cell treatment for PD may not be a good option for all cases, so we request all potential patients to submit recent medical diagnosis and lab results/CT scans to our medical team for review.
Published Clinical Citations
 ^ Agosta, Federica, Ammar Al-Chalabi, Massimo Filippi, Orla Hardiman, Ryuji Kaji, Vincent Meininger, Imaharu Nakano, et al. 2014. The El Escorial criteria: strengths and weaknesses. Amyotrophic lateral sclerosis & frontotemporal degeneration, no. 1-2 (December 8). doi:10.3109/21678421.2014.964258. https://www.ncbi.nlm.nih.gov/pubmed/25482030
 ^ Naujock, Maximilian, Nancy Stanslowsky, Peter Reinhardt, Jared Sterneckert, Alexandra Haase, Ulrich Martin, Kwang-Soo Kim, Reinhard Dengler, Florian Wegner, and Susanne Petri. 2014. Molecular and functional analyses of motor neurons generated from human cord-blood-derived induced pluripotent stem cells. Stem cells and development, no. 24 ( 15). doi:10.1089/scd.2014.0180. https://www.ncbi.nlm.nih.gov/pubmed/25007389
 ^ Phanthumchinda, K, O Supcharoen, and E Mitrabukdi. 1996. Madras pattern of motor neuron disease: case report from Thailand. Journal of the Medical Association of Thailand = Chotmaihet thangphaet, no. 6. https://www.ncbi.nlm.nih.gov/pubmed/8855616
 ^ Sarlak, Golmaryam, Anorut Jenwitheesuk, Banthit Chetsawang, and Piyarat Govitrapong. 2013. Effects of melatonin on nervous system aging: neurogenesis and neurodegeneration. Journal of pharmacological sciences, no. 1 (August 27). https://www.ncbi.nlm.nih.gov/pubmed/23985544
 ^ Terashima, Tomoya, Hideto Kojima, Hiroshi Urabe, Isamu Yamakawa, Nobuhiro Ogawa, Hiromichi Kawai, Lawrence Chan, and Hiroshi Maegawa. 2014. Stem cell factor-activated bone marrow ameliorates amyotrophic lateral sclerosis by promoting protective microglial migration. Journal of neuroscience research, no. 7. https://www.ncbi.nlm.nih.gov/pubmed/24936617