Thursday, July 28, 2022

Stem Cell Treatment For Parkinson’s Disease

Box 2 Advantages Of Stem Cell

#OpenUpStemCells: Dr. Agnete Kirkeby on stem cell treatments and Parkinson’s Disease

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.


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

Is There Any Guarantee That A Stem Cell

There is no therapy, be it an experimental or established treatment, for which your treating physician can promise or even guarantee a therapeutic success. In the case of innovative and experimental therapies such as stem cell therapy, doctors must perform a benefit-to-risk-analysis for each individual case and ensure that the therapy is beneficial to the patient and these benefits outweigh the risks. Only when this is the case, your doctor will suggest treatment with stem cells.

Etiology And Risk Factors

Parkinsonian symptoms can arise from either the neuropathologic condition of PD or other forms of parkinsonism. For neuropathologic PD, about 90% of cases are sporadic, with no clear etiology an additional 10% have a genetic origin, and at least 11 different linkages with 6 gene mutations have been identified Genetic forms of PD are seen more frequently in young-onset PD. A combination of environmental factors or toxins, genetic susceptibility, and the aging process may account for many sporadic cases Secondary forms of parkinsonism can be caused by medications, the sequelae of central nervous system infection, toxins, or vascular/metabolic disorders . The only proven risk factor for PD is advancing age . Other environmental or lifestyle risk factors associated with development of PD are rural living, exposure to pesticides and herbicides, well-water drinking, and working with solvents . However, none of these factors unequivocally has been demonstrated to cause iPD .

Figure 1: Etiology of Parkinson’s Disease . View Figure 1

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Symptoms Of Parkinsons Disease

Parkinsons disease may include many symptoms depending on the severity of the affected person. Early signs of this condition often go unnoticed. However, as the disease progresses, you can expect the following symptoms:

  • Difficulty writing
  • Loss of involuntary movements
  • Slowed overall movements
  • Tremors or shaking

Why Is Stem Cells Treatment Better Than Conventional Treatment Approach For Treating Parkinsons

Stem cell therapy

Conventional treatment approaches highly invasive associated with many side effects. Although stem cells can naturally heal the body from damage and regenerate lost neurons to improve impaired functions. Additionally, since the bodys own cells are used for repairing, the entire treatment is minimally invasive without any side effects.

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Why Choose Our Stem Cell Clinic For Parkinsons Disease

Parkinsons disease is a chronic and degenerative neurological disorder that leads to the loss of neurons in the brain. This leads to uncontrolled shaking, muscle rigidity, and difficulty with walking, speech, and cognition. The stem cell therapy we offer at Shifa Rejuvenation Clinic has been shown to be an effective treatment for Parkinsons Disease.

We use Superior Quality Stem Cells which can help reverse the damage done by Parkinsons disease while also providing relief for patients who suffer from chronic pain.

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.

What are the challenges?

Replacing lost cells

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Does It Work Efficacy Of Commercial Stem Cell Clinics

Commercial clinics do not as a rule publish their results in peer-reviewed journals to demonstrate to the scientific community that the treatments work. Rather, they usually rely on anecdotes from patients as proof of efficacy. Some clinics are tracking their results by measuring variables such as quality of life before or after the procedure. However, without comparing the patients to a similar group who does not receive the treatment, it is hard to know whether any improvement is due to placebo effect or to the treatment itself.

Stage Of Mda Cell For Grafting

How can stem cells treat Parkinson’s?

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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Environmental Causes Of Parkinsons Disease

Parkinsons Disease causes are classified as environmental causes due to the fact that they occur through exposure to certain drugs which has been proven in scientific studies.

The most common sign of parkinsonism is a resting tremor, which causes shaking when the individual assumes or is forced into certain positions.

Other less frequent symptoms are impaired movement and balance problems due to changes in muscle stiffness, slow movements, rigidity, sleep disturbances, mood changes, and difficulty speaking or swallowing.

Symptoms worsen with time as the disease progresses to its final stages where it causes an inability to walk, talk, swallow properly, stay awake for a long period of time.

Advantages And Disadvantages Of Ipsc

Cell-based therapies including MSCs have been tested preclinically and clinically, and many results have shown them to correct a diseased state by replacing degenerating neurons with normal ones . The therapeutic benefits, however, may not be sustained for a satisfactory period of time owing to the presence of endogenous pathological proteins that might affect the transplanted functional cells . When -syn cellcell transfer occurred, -syncontaining LBs gradually appeared in grafted neurons .

Stem cell therapy for Parkinson disease. Dopaminergic progenitors could be obtained from different sources of pluripotent stem cells, which are either derived from somatic cells by epigenetic reprogramming, or from IVF-derived human embryos. HLA-matched iPSC or gene-edited hyopimmunogenic ESC/iPSC lowers the risk of graft-induced rejection. Preclinical tests in neurotoxin-induced PD models in rodents and nonhuman primates show promising therapeutic effect. IVF: in vitro fertilization HLA: human leukocyte antigen.

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Red Flags Raising Concerns About A Medical Tourism Facility

Claims of efficacy only based on patient testimonialsClaims of multiple diseases being treated with the same type of stem cellUnclear documentation of the source of the cells or how the treatment will be doneClaims of little or no riskHigh cost of treatment or hidden costsSuggestions that repeat treatments may be needed if not initially successful

Stem Cell Research And Parkinsons

Parkinson Disease And Stem Cells

The aim of stem cell research in Parkinsons is to understand how nerve cells develop, why some die and how healthy cells can be used to replace damaged brain cells. With this knowledge it may be possible to replace the damaged cells in the brain by introducing healthy dopamine-producing cells generated from stem cells grown in the laboratory. Healthy dopamine-producing cells derived from stem cells could also be useful to researchers in testing new treatments.

Researchers are particularly interested in embryonic stem cells as they have the potential to develop into all types of cells in the body, including the brain. More research is needed in order to understand the way these cells work to ensure that replication can be controlled and a safe treatment developed.

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Assessment Of The Efficacy Of Cell Transplants With Immunostaining Characterization

In the case of mDA progenitor neuron specifications, positive gene expression of common transcription factors FOXA2, LMX1A, and OTX2 and negative markers such as Afp, Gata4, and Brachyury have been quantitatively analyzed . More importantly, the upregulation and downregulation of these markers at a given stage in vitro governs the efficiency of cell fate determination. Unfortunately, these markers have been shown to coexpress in the diencephalic progenitor cells of the subthalamic nucleus . Furthermore, the expression of the positive genetic marker for DA neurons, tyrosine hydroxylase , a rate-limiting enzyme in dopamine synthesis , and the levels of GIRK2 have also been observed in many cell types in vitro . Moreover, common positive markers used to isolate high-quality DA progenitor cells include EN1 and SPRY1 Nurr1 FOXA2, LMX1B, and MSX1 , and the bicoid-related homeodomain factor Ptx3/Pitx3 . It is noteworthy that some discrepancies have been found with the requirement for the presence of floor plate-specific cell surface marker CORIN expression . A more recent study has identified a cell surface marker integrin-associated protein as a positive marker for FOXA2-positive DA progenitor cells .

So What Are Stem Cells

Stem cells are cells that have not yet specialized in the body, meaning they have not grown to a particular type of cell with a specific function . A stem cell can become many different cell types in the human body. The process of stem cells become new types of cells is called differentiation. This process is the most important aspect of stem cell therapies, as the cells become the type of cells required for your body to heal. Stem cells are also self-replicating. This allows them to multiply into identical copies of the stem cells that have already gone through differentiation in the body. For example, if stem cells were used to treat a neurological injury, cells administered during treatment could become nerve cells, and then replicate to create exponentially more nerve cells on their own. This drastically increases the effectiveness of stem cell treatments over time.

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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.

What Can Stem Cell Therapy Do For Parkinsons Disease

Parkinsons – Stem Cell Treatment

Stem cells have been shown to improve the symptoms of patients with Parkinsons Disease. Stem cells from fat may be able to differentiate into new, healthy, dopamine-creating neurons the same cells that are damaged by the disease. Stem cell therapy may also reduce inflammation caused by the condition. See our blogs What are Stem Cells? and Understanding Adipose-Derived Stem Cells to learn more about how stem cells are obtained from fat. Many patients experience improvements in their condition and a reduction in Parkinsons-related symptoms.

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The Promise And Potential Of Stem Cells In Parkinsons Disease

Neurosurgeon Viviane Tabar is co-leading a trial to inject stem cells into the brains of people with Parkinsons disease to restore dopamine levels.Credit: Courtesy of Memorial Sloan Kettering Cancer Center

Neurosurgeon Viviane Tabar has scrubbed in. In front of her is the first participant in a clinical trial to determine whether stem cells can be safely injected into the brains of people with Parkinsons disease. The cells had been frozen, but they are now thawed and sitting on ice, waiting for their moment.

Tabar, a physician-scientist at Memorial Sloan Kettering Cancer Center in New York City, makes an incision in her patients scalp and drills a small hole in their skull. She then uses a brain scan almost like a GPS, she says, to guide her to the putamen a part of the brain in which levels of the neurotransmitter dopamine are unusually low in people with Parkinsons. Once she has confirmed that shes reached the right spot, she injects the stem cells, then repeats the process on the other side of the brain. She hopes these cells will take hold and eventually begin to produce dopamine where otherwise there would be little or none. The surgery itself is minor enough that the patient can go home the next day.

From Cell Replacement To Circuits

A key requirement for cell-replacement therapy to work is that engrafted neurons connect to resident neuronal networks, thereby reconstructing damaged circuits or establishing alternative circuitries that can compensate for the functional deficits elicited by neurodegeneration.

Studies in rodents using allografted fetal VM demonstrate synapse formation from host to graft and from graft to host,. Novel technologies have made the assessment of synaptic integration of hPSC-derived neurons more accessible. For example, retrograde tracing based on modified rabies virus has allowed monosynaptic connections of afferent neurons to and from the graft to be mapped in the 6-hydroxydopamine rat model of PD, and revealed that the host circuitry, specifically nuclei of the intact mesDA system, formed appropriate synaptic contacts with grafted hPSC-derived neurons,. Using the same experimental design, another study demonstrated that grafted neurons also formed synaptic contacts with host circuitry, namely with surrounding striatal medium spiny neurons and neurons of the medial prefrontal cortex that are normally targeted by A10 DA neurons. These studies demonstrate that synaptic integration between host and transplanted neurons is a dynamic process, starting as early as 6 weeks after transplantation and maintained for at least 6 months, that occurs between reconstructed physiologically relevant circuits.

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Stem Cell Therapy For Parkinsons Disease

Parkinsons disease is a progressive disorder of the nervous system affecting movements. It develops gradually, starting with the barely noticeable tremors but in the later stages, it is associated with frequent body stiffness and slowing-down or complete loss of movement. People with Parkinsons disease may experience muscular tremors, stiff muscles, delayed muscular movements and issues with locomotor actions such as balance, walking, etc. With recent technological advancements in stem cells, it is possible to proactively alter the effects of the disease and live a full, happy, healthy life. Having the potential to significantly impact the development of diseased state, stem cell treatment for Parkinsons can create dopamine-producing cells which enhance normal communication between neurons and provide a vastly improved quality of life.

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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Gmp Cryopreservation Of Cells

The generation of good manufacturing practice -compliant, deliverable midbrain DA progenitors/neurons optimized for cell-based therapy for PD is a major challenge. Currently, a diverse collection of clinical-grade hESC lines are available as starting material to generate GMP-compliant mDA progenitors/neurons. In fact, GMP compliant differentiation protocols and reagents have been successfully applied to generate GMP mDA neurons .

The Future Of Stem Cell Therapy For Parkinsons

Four groups dedicated to using stem cell therapies to treat Parkinsons disease have formed an international consortium known as G Force PD. Each of the four centers is planning a clinical trial to start in the next 1-4 years. They differ on the source of stem cells that they will be using . All will be injecting the cells directly into the basal ganglia part of the brain where the ends of the dopamine producing neurons live. The Parkinsons community eagerly awaits the implementation of these trials.

When open for enrollment, should I consider participating in a stem cell trial?When faced with an illness like PD, you can at times feel that it is worthwhile to try anything that may lead to a cure. Its important to always make sure however, that youre dealing with trusted information, proven therapies, and clinical trials that have been properly vetted by the medical community.

Therefore, in order to use safely, focus on the trials conducted at academic medical centers in the United States. Once you have identified a trial that you might be interested in, talk it over with your doctor before committing to anything.

Be aware that a clinical trial utilizing stem cells will likely require the cells to be injected directly into the brain, which will inevitably be associated with a certain amount of risk. You will need to discuss details of this risk with your doctor and the trial organizers.

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