Parkinsons Disease And Its Treatment
Parkinsons disease is the second most common neurodegenerative disease worldwide, yet remains without a cure. Typical motor symptoms of Parkinsons disease are slowness of movement, tremor and stiffness and later also gait difficulties. It is not well known how the disease arises or develops, but the core pathology common to all patients is the loss of dopamine neurons in the midbrain.
The treatment of Parkinsons disease has for over 50 years relied on symptomatic pharmacological therapies that are highly effective, especially in the early years of the diagnosis. However, such therapies are ultimately limited by the development of side effects that relate to the systemic delivery and non-physiological dopamine levels. Targeted regenerative cell therapies designed to restore specifically the lost dopaminergic input to the motor system of the brain would therefore represent a major advance in treating Parkinsons disease.
What Are The Early Signs Of Parkinsons Disease
Early symptoms and possible warning signs of Parkinsons disease are: Writing becomes difficult and font is getting involuntarily smaller One sided tremor or shaking Involuntarily index finger and thumb rolling Dizziness or fainting Change of facial expression known as mask face Soft or lower voice then usual Sleep problems usually accompanied with sudden movements Walking and otherwise subconscious movements only seem possible when actively imitating them Hunching over or stooping
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Box 2 Advantages Of Stem Cell
Stem cell-derived cells have several advantages over fetal cells, including near-unlimited availability, standardized manufacture, the ability to be cryopreserved, and increased purity, allowing more facile surgery, dosing and distribution.
Availability
Human fetal brain tissue to be used for transplantation is scarce. To obtain sufficient surviving dopamine neurons in the transplants, the ventral mesencephalon of at least three fetuses must be collected and transplanted into each hemisphere. Moreover, the cells remain viable for only a short time in hibernation medium, meaning that all the material used for grafting in one patient must be collected over a short period. The earlier fetal VM transplantation trials used tissue from surgical terminations of pregnancy, but now medical terminations are often used in clinics. Although this change does not preclude tissue use, as fetal tissue is subject to carefully defined criteria, the collection is more challenging, the embryos are often too young, and supply determines surgical transplantation date. By contrast, human pluripotent stem cell -derived DAergic neural progenitors can be produced in near-unlimited numbers, cryopreserved and used on demand.
Standardized manufacture
Surgery, dosing and distribution
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Stem Cells For Parkinson’s Disease Are Safe And Effective
According the 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 to be 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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Stem cell therapy for Parkinson’s disease is currently under trials and research. With the use of oral placenta as stem cells treatment for Parkinson’s disease has produced amazing results. The results seen will never be realized with the current medical treatment.
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Stage Of Mda Cell For Grafting
Over the last decades, fetal tissue transplantation studies have provided tremendous insights how to reconstruct the damaged brain of a PD patient. One such aspect was the discovery of the optimal window for isolating mesencephalic cells from fetal tissue. Human mDA neurogenesis occurs during a narrow window of early CNS development at week 68.5 p.c. . Interestingly, human fetal grafts derived from tissue later than 9 weeks showed reduced survival, particularly when injected as cell suspension, and did not reliably yield functional mDA neurons in vivo . In contrast, tissue derived from fetuses at 5.58 weeks p.c. has yielded the best results in pre-clinical and clinical results with robust survival of mDA neuron rich grafts. One additional important point regarding the age of the donor may be the differential yield in production of mDA neuronal subtypes. Rodent studies have implicated that the younger E10 tissue gave rise to 75% GIRK2 + mDA neurons in intrastriatal grafts whereas older E12 tissue contributed 60% of GIRK2 + mDA neurons possibly due to staggered birth timing of A9 versus A10 mDA neurons .
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Which Stages Of Parkinson’s Disease Can Be Treated With Stem Cells
The treatment of Parkinsons Disease with any stem cell method is independent of the stage. Stem cells secrete many healing factors, which can potentially induce a flourishing effect on local resident cells, as well as anti-inflammatory effects wherever they are deployed. This has very positive effects on PD at all stages. However, anticipated results may vary are depending on the progression the treatment plan and the side medications. .
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Twitching Fingers Were Daves First Sign
He asked me if I had any concerns about my health, and I told him I was worried about my cholesterol, and oh, by the way, Ive noticed in the past three or four months I occasionally have an involuntary twitch with my index and middle finger on my left hand.
There are many different types of tremor. What are the differences?
Finger Twitching
The pill rolling tremor that is often described in medical texts refers to the tremors of the fingers, usually the thumb plus the other fingers, that makes it look as if the person is rolling a pill in the fingers. This is most often the part of the body where tremors will begin.
Jaw Tremors
Jaw tremor is common in Parkinsons, whereas head tremor is not. The jaw tremor looks very much like shivering, although usually slower. It goes away with movement, so it is not present while chewing. It is extremely irritating when it is severe enough to cause the teeth to click together. For people with dentures, it may keep the dentures from staying in place, in addition to attracting attention because of the clicking sounds. Chewing gum stops the tremor.
Foot Tremors
Tongue Tremor
Sometimes the tongue has a tremor, and in about 1% of Parkinsons disease cases the head shakes. Sometimes the head tremors because the arms are shaking and the tremor is simply transmitted. The voice, while frequently involved in Parkinsons, is never involved by tremor.
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Stem Cell Treatment For Parkinsons 2022 Protocol
In Parkinsons 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 . According to the theory, the stem cells in the mind of the patient
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What Have Clinical Trials Found
Until the discovery of the process of creating iPSCs, the only stem cell therapies for Parkinsons disease required the use of embryonic stem cells. This came with ethical and practical challenges, making research more difficult.
After iPSCs became available, stem cells have been used in clinical trials for many conditions involving neural damage with overall mixed results.
The first clinical trial using iPSCs to treat Parkinsons disease was in 2018 in Japan. It was a very small trial with only seven participants. Other trials have been completed using animal models.
So far, trials have shown improvement to symptoms affecting movement as well as nonmotor symptoms such as .
Some challenges do arise from the source of the stem cells.
Stem cell therapy can be thought of as being similar to an organ transplant. If the iPSCs are derived from a donor, you may need to use immunosuppressant drugs to prevent your body from rejecting the cells.
If the iPSCs are derived from your own cells, your body might be less likely to reject them. But experts believe that this will delay stem cell therapy while the iPSCs are made in a lab. This will probably be more costly than using an established line of tested iPSCs from a donor.
What Are The Advantages Of Human Umbilical Cord Mesenchymal Stem Cells
- Abundant supply containing up to 10 times more stem cells than bone marrow or adipose derived stem cells
- hUC-MSC have immunosuppressors and immunomodulatory properties that allow their use in any individual without rejection- Human Leukocyte Antigen matching is not necessary
- Greater proliferation ability than adult autologous stem cells
- They regenerate at a very rapid rate
- They are young and very adaptive
- They have not been impacted by the aging process
- They have not been affected by environmental toxins
- Umbilical cord stem cells can be administered multiple times over the course of days
- Eliminates the need to collect stem cells from the patients fat or hip bone reducing pain and recovery time
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Confusion With Essential Tremor
The tremor of Parkinsons disease is often confused with the tremor of a condition called Essential Tremor, or Benign Familial Tremor. Katherine Hepburn had Essential Tremor, and was originally misdiagnosed with Parkinsons. Ronald Reagan, also, had Essential Tremor. Both had a head tremor and a vocal tremor. With Essential Tremor, the hands are most commonly involved, followed by the head and then the voice. Essential Tremor can cause the jaw to tremor, and it may be difficult to figure out if a jaw tremor is from Essential Tremor or Parkinsons. Unfortunately, some people may have both disorders. Some authorities believe that there is, in fact, an increased association between the two conditions, so that more people with Parkinsons disease have Essential Tremor than would be expected by chance alone, but this has not been established.
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Overview Of Parkinson’s Disease
James Parkinson revealed a detailed description of six patients with shaking palsy in 1817 and after his death, the mentioned description known as Parkinson’s disease , which is now the most common neurodegenerative disorder after Alzheimer’s disease. The pathological hallmark of PD is the degeneration of dopaminergic neurons of the substantia nigra pars compacta . The loss of this neuronal population results in functional imbalances in the nigrostriatal pathway, leading to lowering the level of dopamine in the striatum. This leads to motor dysfunction and the development of the classical symptoms of PD. Motor symptoms including resting tremor, bradykinesia, and rigidity of skeletal muscle, postural instability, stooped posture, and freezing of gait are clinical symptoms in PD. Furthermore, non-motor symptoms such as cognitive and behavioral problems, besides sensory impairments are seen in the patients. The prevalence of PD is approximately 0.3 % in the general population in developed countries and affects about 1% of those older than 60 and it is unusual to occur before the age of 50. Notably, men are at higher risk than women.
Fig.1 The dopaminergic neuron and the nigrostriatal pathway.
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Parkinsons Disease: How Could Stem Cells Help
What do we know?
Tremors, muscle rigidity and other symptoms of Parkinsons disease are caused by the death of dopamine-producing neurons in the brain. Dopamine producing neurons throughout the brain are affected, but the substantia nigra is the primary brain region where neurons are lost.
People affected by PD often develop abnormal protein clumps in their brain called Lewy bodies. These clumps are made of a protein called alpha-synuclein.
Levodopa is the primary drug used to treat PD. Levodopa is converted into dopamine when in the body, which compensates for lost dopamine-producing neurons.
What are researchers investigating?
Approximately 5% of people with PD have inheritable gene mutations linked to PD. Researchers are investigating what causes PD in the other 95% of patients in clinical studies, animal models and cell models.
Transplantation of young brain cells from human foetuses into people with PD has shown promising results in previous clinical trials. The current TRANSEURO study is re-examining this treatment method with the aim of minimising side effects and measuring efficacy.
Scientists can now make dopamine-producing neurons from both human embryonic stem cells and human induced pluripotent stem cells . Neurons made from human ESCs and iPSCs mature into human dopamine-producing neurons, survive and function after transplantation into mouse, rat and monkey models of PD.
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Stem Cell Therapy For Parkinson Disease In Pakistan
Stem cells are cells that have the ability to differentiate into any other cell type. They can also divide and renew themselves, meaning they can be used for regenerative purposes. It has been found stem cells are of particular importance in cases of Parkinsons disease because these stem cells produce dopamine. This is important because Parkinsons patients suffer from a lack of dopamine production which leads to tremors, speech problems, and more! Additionally Stem cells are the bodys true multi-potentiality cells to treat diseases like diabetes, heart problems and now Parkinsons treatment is possible through stem cell therapy. Stem Cells have developed rapidly and provided a new ray of hope to many patients all over the world suffering from Parkinsons disease.
Impact Of Tremor For Patients With Early Stage Parkinsons Disease
Patients with early stage PD consistently rank tremor as highly important, even when asked to consider other diverse aspects of their condition. Tremor was cited as the most bothersome symptom in a survey of 75 PD patients with relatively mild symptom severity . Twenty-eight percent of patients mentioned tremor in their open-ended response to the question, Which two problems related to Parkinsons disease bother you most?
The psychosocial impact of tremor for many PD patients is insidious and profound and goes well beyond a general annoyance . During an in-depth structured interview , patients and caregivers shared emotional and highly compelling stories of trying to disguise tremor during the early stages of PD by wearing clothes with pockets or hiding an affected hand behind ones back. They went further to express dreading the progression of their tremor during later stages of PD with remarks such as, as it changes to slavering and trembling in a corner, I will find that a horror.
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Moral Positions Concerning The Use Of Hesc For Medical Treatment
Participants moral positions regarding the use of embryos for therapy development were diverse. It was perceived as a complex and difficult issue that some individuals had never thought of, and it triggered thoughts and feelings. One person asked herself how much one should change the course of nature.
How far should we go in changing , as in genetics, uhm, where do we draw the line on what is ethical, that is what I think about a lot…
Some had no firm opinions, while others were clear about their positions. More knowledge of the effects of the treatment was important for some to make a decision. Some thought it should be up to the experts, researchers or legislators to decide whether the embryos should be used for medical purposes.
It is up to the researchers to use them in a right way…one has to follow the current legislation. I have no concerns in my conscience regarding this.
So my first was that I will not say it was all negative, but it was in the negative direction this feels a bit tricky. What are they going to do with it? What are they after? I dont understand.
In this case, a person with Parkinsons has lost something existing if you can replace it in this way, then I dont see an ethical problem with it at all
I find it harder to accept that you, in some way, improve nature, but replacing what has been lost is not problematic at all to me.
Genetic Testing For Parkinsons
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 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 or ALS/MND. The most common genetic markers used for screening hereditary Parkinsons include LRRK2, Glucocerebrosidase , 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 Parkinsons 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
TREATMENT PRECAUTIONS & RISKS
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