Parkinsonism: Parkinson’s Disease, Manganese Exposure and Possibility of Stem Cell Therapy

Parkinsonism that includes Parkinson’s disease has shown abnormal levels of dopamine in patients. Dopamine is naturally produced by dopamine neurons at the basal ganglia of the brain. This dopamine is a neurotransmitter that controls the pleasure centers of the human brain. In addition, dopamine regulates body movements. It is also responsible for the emotional responses in the human mind.

However, with age, the levels of dopamine produced can get reduced. This could be due to poor function of dopamine neurons. Also, there could be damaged/destroyed cells that do not respond to produced dopamine. These conditions give rise to tremors, rigidity, poor balance and slow movements that are common symptoms. People showing these common symptoms are diagnosed with Parkinsonism Syndrome.

Below is the List of Several Types of Parkinsonism

• Atypical Variants (Parkinson’s Plus Syndrome): The people suffering from Atypical Variants are few since the illness is rare. There are several types of Atypical Variants Parkinsonism given below:
  • Multiple System Atrophy (MSA): The people suffering from Multiple System Atrophy suffer from several disorders that damage many body systems. MSA are mainly of two types – MSA-P (Symptoms dominant) and MSA-C (Base of brain/cerebellum dominant).
  • Olivopontocerebellar atrophy (OPCA)
  • Shy-Drager syndrome (SDS)
  • Striatonigral degeneration (SND)
• Classic Parkinson’s disease (Idiopathic): There are many people suffering from Classic Parkinson’s disease (PD). However, the exact cause of the illness is not known. Hence, the illness is also known as idiopathic.
• Corticobasal Degeneration (CBD): The people suffering from Corticobasal Degeneration get jerking, cannot control their limbs that are not even weak. These patients are treated with Botox (botulinum toxin) for relaxing their limbs.
• Lewy Body Dementia (LBD): The people suffering from Lewy Body Dementia are second most common amongst the elderly after Alzheimer’s disease. The LBD patients get the deposition of Lewy proteins clumps in several parts of their brain. As a result, they show symptoms of the gradual decline of cognitive, hallucination, and speech problems.
• Progressive Supranuclear Palsy (PSP): The people suffering from Progressive Supranuclear Palsy are always after the age of 50. The patients show faster progress of their illness than patients suffering from Classic Parkinson’s disease. Generally, the patients have eye movement problems. Their vision becomes poor and blurry. Also, they fall frequently and end up getting dementia towards the end of their lives.

Other Neurological disorders also cause Parkinsonism Syndrome. Details are discussed below:

• • Essential Tremor: The people suffering from Essential Tremor often get the illness due to family history. This illness is often passed down as a hereditary disease through genetics. The patients with Essential Tremor show their symptoms mostly in their hands. Also, their symptoms get worse over time.
  • Environmentally Caused Parkinsonism: The people suffering from Environmentally Caused Parkinsonism show symptoms for taking certain drugs. Below is the list of drugs (prescribed and non-prescribed) that cause symptoms of Parkinsonism:
    • Antipsychotics – Haldol (haloperidol) and Thorazine (chlorpromazine)
      
    • Depakote (Valproic acid)
      
    • Opioid – MPPP (desmethylprodine) contaminated with the neurotoxin MPTP
      
    • Reglan (metoclopramide)
      
    • Serpasil (reserpine)
      
    • Stimulants, including amphetamines and cocaine
      
    • Xenazine (tetrabenazine)
  • Normal Pressure Hydrocephalus (NPH): The people suffering from Normal Pressure Hydrocephalus show abnormal fluid retention in their ventricles of the brain. These patients get their extra fluid from the brain drained to the abdomen through a shunt.
  • Postencephalitic Parkinsonism: The people suffering from Postencephalitic Parkinsonism get infected by a parasitic disease called African trypanosomiasis/sleeping sickness. The patient has swelling of the brain and/or spinal cord.
  • Post-Traumatic Parkinsonism (Punch-drunk Syndrome): The people suffering from Post-Traumatic Parkinsonism get sick due to severe head injuries caused by boxing/football. These patients end up getting Chronic Traumatic Encephalopathy (CTE), sort of dementia.
  • Vascular Parkinsonism (Arteriosclerotic Parkinsonism): The people suffering from Vascular Parkinsonism get the illness after experiencing several small strokes. These patients get symptoms of Parkinsonism all of a sudden or sometimes slowly and gradually. The patient does not get tremors. However, the patient shows problems in their legs but, with time they can become normal. It has been observed that Vascular Parkinsonism progresses slower than other Atypical Parkinsonism.

Treatment for Parkinsonism Excluding Parkinson’s Disease

Drug-induced Parkinsonism can be cured by stopping or reducing the dosage of the medication. Other methods of treating Parkinsonism include Antidepressants, Physical therapy, and Speech therapy.

How do Parkinsonism and Parkinson’s Disease Differ?

Parkinsonism Syndrome comprises several neurological illnesses as discussed above. You already know that the most common one is the Classic Parkinson’s disease (PD). The people suffering from Parkinson’s disease (PD) also get tremors, rigidity, poor balance and slow movements. These symptoms are treated with medicines to ease their symptoms and prolong their healthy life. The patients of Parkinson’s disease respond well to the medications prescribed for the symptoms. Also, their MRI reports are always normal.

Causes of Classical Parkinson’s Disease

Classical Parkinson’s disease (PD) is also caused due to the shortage in production and use of dopamine. Lewy proteins are normally made in the body. However, clumps of Lewy Proteins known as Alpha-synuclein are not normal. In PD patients, Lewy clumps are discovered in the brain controlling sleep and smell. Yet, the reason why PD patients suffer from tremors, rigidity and slow movements is unknown.

List Showing Factors that can Cause Parkinson’s Disease (PD)

• Age: Parkinson’s disease is common amongst elderly people who are aged 60 or over. PD is not found amongst youngsters.
• Gender: Men suffer from Parkinson’sdisease more than women.
• Genetics: External environment can cause gene mutation or modification of the normal gene. This results in making abnormal proteins within the body. Lewy proteins synthesized in the body are common and normal. However, clumps of Lewy proteins that are found deposited in the PD patients’ brains are abnormal.
• Hereditary: Genes are passed down from ancestors to later generations. If anyone from your mother’s or your father’s side suffered from PD, then you might get it. Yet, it is not necessary to inherit directly from a parent. This is because your generation can skip getting the gene causing PD.
• Environment: People exposed to toxic materials found freely in the environment. These include certain agricultural chemicals used as insecticides, herbicides, fungicides. There are common metals and chemicals present naturally in the environment that can cause PD. One such compound is Manganese.

The details on how Manganese causes Parkinson’s disease have been discussed below:

Manganese is used as one of the three essential trace elements in the human body. Adequate amounts of Manganese are found in consumed foods. These include eggs, grains/rice, green beans, herbs, nuts, olive oil, oysters, soya beans, spinach and tea. After absorption, the blood transports manganese to the liver, kidneys, pancreas and endocrine glands.

If there is a shortage of manganese intake, then the human body suffers from numerous ailments. These include birth defects, blood clotting, hair color changes, fatness, glucose intolerance and lowered cholesterol levels. In addition, the human body suffers from neurological symptoms, skeleton disorders and skin problems.

If there is an excess of manganese, then the human being forgets, hallucinates and gets damaged nerves. In the case of men, there might be impotence. Additionally, excess manganese causes bronchitis (respiratory tract problem), lung embolism and Parkinson’s disease. Also, Manganese causes syndrome showing Schizophrenia’s symptoms, dullness, headaches, insomnia and weak muscles.

Overexposure of Manganese through inhaling dust or fume damages the central nervous system permanently. Sometimes, people end up with pneumonia and other respiratory infections. Their symptoms include convulsive gait, emotional disturbances, frequent leg cramps, laziness, paralysis, sleepiness and weakness.

You should ensure you are not suffering from Parkinson’s disease. If you have the illness, then your symptoms can be treated to improve your life. Here is the list of early symptoms of Parkinson’s disease (PD):

• Constipation: You would get constipated even after drinking enough water and eating foods with high fiber. After taking flax or other over-the-counter medication, if you are constantly constipated, see your doctor.
• Dizziness and/or Fainting: You suddenly get dizzy or feel faint especially after standing up from sitting down position. This occurs due to low pressure so consult your doctor.
• Hunching Over: You notice that you are hunching over. Often, your close relative who lives with you would notice this trait in you. Ensure you have not become like so due to any injury or aches and pains. If not, then consult your doctor.
• Masked Face: You notice that your face looks down and depressed even if you are in good mood. This is commonly called “facial masking”. Ensure you are not taking medication that makes you look staring or abnormal. If not, then consult your doctor.
• Small Handwriting: You notice that your handwriting has become smaller and more crowded on the page. This is called “micrographia” then you need to consult your doctor. Of course, with age, your hands and fingers can become naturally stiff and your vision can also deteriorate. If so, then consult your doctor.
  

• Smell Difficulties: You cannot smell strong odors of foods such as bananas and others. Ensure your nose is not stuffy and you are not suffering from common cold. If not, then consult your doctor.
• Tremor: You notice that while you are resting, your chin, finger, hand or thumb are shaking. With age, you can also experience tremors or shakings after you exercise. You can get tremors due to stress and/or injury. Also, certain medications you have intake causes tremors. Since tremors are one of the most significant and common symptoms, consult your doctor.
• Trouble Moving/Walking: You feel stiffness in your body. This is especially in the arms and legs such that you cannot move or walk. Ensure you are not suffering from arthritis that may cause stiffness in the body. If not, then consult your doctor.
• Trouble Sleeping: You notice that you are moving along with your dreams at night. Also, your sleep has decreased such that you are awake mostly throughout the night. You awake early in the morning and sleep during the day. Of course, in normal circumstances, some people suffer from trouble sleep or insomnia. However, consult your doctor who can prescribe appropriate medication for you.
• Voice: You would notice your voice has turned soft and you are sounding husky. Ensure you do not have voice changes caused by chest cold and other viral infection. If the voice change persists, then consult your doctor.

Above are the early signs of Parkinson’s disease (PD). It is recommended that you consult your physician to eliminate the illness. However, if you are suffering from PD, your physician would arrange for the necessary treatment. If you ignore the mentioned early symptoms of PD, then you can end up with complex ones. The list has been discussed below:

• Bladder problems: You would notice that you cannot control your urine and/or you are facing difficulties in urination. This condition is caused due to bladder problems that store urine in your body.
• Chewing problem: You would notice that you cannot chew especially during the late stages of PD. Your mouth’s muscles would stop working properly and well. Since you would suffer from chewing issues, you can get choked or get malnutrition.
• Depression/Emotional changes: You might get depressed or you might notice emotional changes. This is caused because of the reduced dopamine levels.
• Fatigue: Your energy levels get reduced very rapidly. As a result, PD patients feel tired and fatigued especially later during the day.
• Pain: You might feel pain either in certain areas or all over the body.
• Sexual dysfunction: Men with PD often notice their reduced interest in sexual desire and performance.
• Sleep disorders: You would notice more complex sleep disorders than you noticed in the early signs. As mentioned you would frequently awake during the night, awake early and sleep in the day. In addition, you might get quick eye movement along with sleep disorder. You might also act out your dreams. Your doctor would provide you with proper medications.
• Smell dysfunction: You would notice that you cannot smell certain odors or you cannot distinguish the differences in smell.
• Swallowing problem: You would notice that you are finding it difficult to swallow while PD progresses. Your saliva would get accumulated in your mouth. Since you would experience slow or reduced swallowing, you would end up drooling.
• Thought difficulties: You would notice you are having difficulties in your thought process. You lose track of what you were saying and cannot continue with the conversation. This is caused due to cognitive issues common in Dementia, Alzheimer and Parkinson’s disease.

After your doctor diagnoses that you are suffering from Parkinson’s disease, you would be advised to follow the processes as below:

• Meet with a Neurologist:

Your neurologist has specialized in controlling or curing illnesses related to the brain. Generally, your neurologist would prescribe Levodopa. This particular medicine aids in incrementing dopamine levels in the brain. Yet, Levodopa may not provide positive results especially when brain cells are damaged/destroyed and do not respond. Instead, often your doctor prescribes medications to control your signs and symptoms. As a result, you might have to take several sorts of medicines throughout the day. The best news your body responds well if you are suffering from PD. However, there is no medicine that reverses the effects of PD as of today. In addition to taking medicines, the patients of PD are advised to exercise, rest, and undergo surgery.

• Work with Therapists (Occupational, Physical and Speech):

The therapists are trained to work with patients of PD. Working with them help patients in mainly two aspects namely Physical and Mental. Physical aspect helps in improving (balancing, flexibility, motor coordination, posture, strengthens grip, tremors and walking). Mental Aspects helps in enhancing (energy, mental health, mood, and sleep).

• Regular Exercising:

If you are a PD patient, then chances are you are not very young anymore. Hence, take proper guidance to exercise correctly and regularly. There are several interesting exercises you can choose from. These include cycling, dancing, running, skipping, tai chi and yoga. Before selecting your exercise, consult your doctor and trainer to find what is best for you to practice.

• Meet with Social Worker:

The social worker would educate you and your family about PD. All family members should know how to cope with PD and its signs and symptoms. After sessions with social workers understanding PD better, you should inform other family members and friends.

Research Studies on the Alternative Cure of PD Using Stem Cell Technologies

Before using Stem Cells, research scientists used animal models and PD patients for screening medicines. However, since 2007, there has been a breakthrough and discovery of treating PD with stem cells. The list of already known stem cells is shown below:

• Adult Derived Stem Cells (Tissue-specific Stem Cells):

These stem cells are found in the adult and can be isolated from the adult. This stem cell grows into only the specific sort of cell type derived from the particular tissue. Also, this stem cell of that particular tissue grows into that original organ during development.

The most understood Adult Derived Stem Cells are known as “Hematopoietic stem cells”. These Adult Derived Stem Cells are found and isolated from the bone marrow. Clinically, these tissue-specific stem cells are utilized clinically for making blood cells. These special cells are meant for treating blood cancer, blood disorders and problems of the immune system.

These stem cells have been isolated from the abdomen, bone marrow, brain, heart, and muscle. Generally, these tissue-specific stem cells are used for maintenance and repair of the organ. This is because the tissue-specific stem cells multiply and develop into the tissue and organ of origin. These stem cells are called “pluripotent”.

• Embryonic Stem Cells (ESC):

These stem cells are isolated from the human embryo during the very early development stage. These days, in vitro fertilization (IVF), are carried out in the laboratories. But, these are not fetal stem cells. The Embryonic Stem Cells are obtained from older embryos. These Embryonic Stem Cells can be coaxed and modified to make all types of human cells. Since these embryonic stem cells can be developed into several cell types, they are called “multipotent”.

• Human Parthenogenetic Stem Cells:

These stem cells are made from an unfertilized human ovum.

• Induced Pluripotent Stem Cells (iPSCs):

These stem cells are man-made from adult skin and/or blood cells. These are programmed to revert to an embryonic state and develop to any desired cell type. In 2007, Induced Pluripotent Stem Cells (iPSCs) were found to help in Parkinson’s disease treatment. Research scientists were able to create a disease model of PD to test new drug reactions.

• Mesenchymal Stem Cells (Stromal Cells):

These stem cells are commonly present in several tissues. These include bones, cartilage and fat. Though significances of stromal cells are not understood, yet these cells tend to grow and regenerate rapidly. These stromal cells are created especially in commercial stem cell clinics.

• Umbilical Cord Stem Cells:

These stem cells are mostly obtained after the delivery of a baby. This is the best source of “Hematopoietic stem cells” from the umbilical cord stem cells. Clinically, these Umbilical cord stem cells can be utilized for treating blood cancers and some rare genetic disorders.

Since 2007, research scientists already know that stem cells can be used for curing PD. Induced Pluripotent Stem Cells (iPSCs) have been used to generate dopamine neurons. Yet, they cannot decide whether to use ES or iPSCs for treating PD patients. Studies have to be made to understand the quality and the quantity required for the necessary therapy. The reason is that both ES and iPS are not compatible with the working in the brain. Hence, some scientists doubt the positive effect of the known stem cells.

Four groups have been formed. Each devotes their time in using special stem cells for treating PD. These four groups formed the international consortium called “G Force PD”. Each group has decided on the clinical trial starting in the next four years. Every group would use different sources of stems cells (ECs vs iPS). The groups would directly inject these stem cells into the basal ganglia segment of the brain. The main objective is to find which source of stem cell generates the maximum dopamine neuron. The Parkinson’s community is anxiously waiting and hoping to see positive results.

The Michael J. Fox Foundation provides funds for PD research and development. It supported the discovery of Embryonic Stem cells (ES) to provide an abundant source of dopamine neurons. Now, there are several other state and federal resources providing funds for the same cause.

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