Current Status Of Stem Cell
- 1Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore, Singapore
- 2Department of Diagnostic Radiology, Singapore General Hospital, Singapore, Singapore
- 3Neuroscience & Behavioral Disorders Program, Duke University and National University of Singapore , Graduate Medical School, Singapore, Singapore
- 4Department of Neurology, National Neuroscience Institute, Singapore General Hospital Campus, Singapore, Singapore
- 5Lee Kong Chian School of Medicine, Nanyang Technological University, Novena Campus, Singapore, Singapore
Disadvantages Of Stem Cell Approaches
While the stem cell approaches described potentially offer promising treatment approaches, a number of problems must be overcome in order for them to be used as a mainline treatment for PD.
Of course, any grafting therapy will require a neurosurgical procedure, and it must be demonstrated that this can be achieved safely, with minimal risk. Additionally, for allogenic grafts a period of immunosuppression will be required, with the associated risk of infection and malignancy. Having said this, there is postmortem evidence of FVM graft survival for over two decades, with only a transient period of immunosuppression, and taking into account the fact that the central nervous system is an immune-privileged site, it is unlikely that this will be a major problem .
It has been estimated that generating iPSCs from 150 human leukocyte antigen -typed individuals could allow for the development of haplobanks which would be able to provide HLA-matched cell products for over 90% of a population . This would mean that rather than an autologous grafting product being produced for each patient, that an iPSC line could be selected with which they were HLA compatible to generate a matched cell product. However, in order to achieve this, a degree of HLA mismatch would be necessary, and a period of immunosuppression would therefore probably be required. Additionally, this would still have significant economic costs .
Assessment Of The Efficacy Of Cell Transplants With Imaging
Last, concurrent with the high demand for the optimization of cell graft visualization in PD, growing emphasis has been placed on enhancing the sensitivity and precision of the spatiotemporal resolution of functional neuroimaging. En route to successful cell transplantation as a therapeutic regenerative method for Parkinsons disease, neuroimaging techniques have to be employed for better patient care. Some key features required to elucidate the therapeutic efficacy of transplanted cells for clinical diagnostics are innervation, survival, differentiation, and functional biochemistry composition. Furthermore, it is crucial that these imaging techniques are time efficient, safe, non-invasive, and allow repeated measures in an individual to determine longitudinal post-operative progression in patients with cell transplantation . In this section, we summarize the pros and cons of current imaging modalities used in tracking cell grafts in PD and their respective biomarkers .
Table 2. Imaging modalities used in cell transplantation for PD.
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First Transplant Trial Of Lab Made Dopamine
Following successes in monkeys, researchers in Japan have announced a clinical trial to transplant dopamine-producing brain cells made in the lab from iPS cells will start in 2018.
We will eagerly be awaiting more information and the outcome of this and the other trials mentioned in this post and hope that it will contribute to more research in this area, and future opportunities for those in the UK to take part.
Potential of this type of therapy: Dopamine-producing brain cells are the type of cell lost in Parkinsons and transplanting them into the brain may be the best hope for repairing the damage and reversing the condition, making this study one of the most exciting ones to follow going forwards. Potential challenges to this approach are all about safety these techniques are still very new, so we dont know much about the long-term safety of lab-made cells.
Stem cells definitely hold huge potential for developing therapies for Parkinsons, but we still have a number of questions to answer and challenges to address before they will be a therapeutic option for people with the condition. We still dont know enough about if these transplant therapies will improve both motor and non-motor symptoms of Parkinsons, such as problems with thinking, memory, pain, and anxiety. We also need to know:
Next Step: Human Trials
Dr. Kordower told MNT that the results of this study give him great confidence going forward into patients.
Dr. Kordower will be a principal investigator in a clinical trial that he expects to take place in 2023, which will study a specific population of individuals with PD who have mutations in the Parkin gene .
These individuals experience degeneration of the dopamine system. While they experience motor dysfunction typical with PD, they do not develop cognitive decline or dementia. So, that makes the perfect test to see whether cell replacement strategies can be helpful, Dr. Kordower told MNT.
If the trial is successful, larger trials may follow in a broader population of people with PD. However, it is important to note that while the findings from this study are promising, results from animal models do not always translate into human clinical trials.
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What Is Parkinson’s Disease
Parkinson’s Disease is a degenerative nervous system condition that affects one’s movement. Symptoms often start quite gradually, with minor issues such as small tremors within the extremities . Currently, there is no cure for Parkinson’s Disease but certain medications do have the capacity to help manage symptoms. Some doctors may also recommend surgery to address certain symptoms, which involves regulating certain areas of the brain.
What Tests Will Be Done To Diagnose This Condition
When healthcare providers suspect Parkinsons disease or need to rule out other conditions, various imaging and diagnostic tests are possible. These include:
New lab tests are possible
Researchers have found possible ways to test for possible indicators or Parkinsons disease. Both of these new tests involve the alpha-synuclein protein but test for it in new, unusual ways. While these tests cant tell you what conditions you have because of misfolded alpha-synuclein proteins, that information can still help your provider make a diagnosis.
The two tests use the following methods.
- Spinal tap. One of these tests looks for misfolded alpha-synuclein proteins in cerebrospinal fluid, which is the fluid that surrounds your brain and spinal cord. This test involves a spinal tap , where a healthcare provider inserts a needle into your spinal canal to collect some cerebrospinal fluid for testing.
- Skin biopsy. Another possible test involves a biopsy of surface nerve tissue. A biopsy includes collecting a small sample of your skin, including the nerves in the skin. The samples come from a spot on your back and two spots on your leg. Analyzing the samples can help determine if your alpha-synuclein has a certain kind of malfunction that could increase the risk of developing Parkinsons disease.
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Some Key Questions To Ask About Unproven Therapies Being Offered Abroad
Have pre-clinical studies been published, peer-reviewed and repeated by other experts?Do the providers have independent committee approval, e.g., Institutional or Ethics Review Board, to ensure risks are as low and worth any potential benefits, and that patient rights are being protected?Do the providers have approval for the safe conduct of clinical trials or medical use of a product for PD from a national or regional regulatory agency, e.g., FDA or the European Medicines Agency?What are the alternative treatment options for my condition?If I have this treatment, can I participate in otherclinical trials or have other interventional treatment options?What compensation am I entitled to if I am injured as a result of participating in this therapy?What are the total costs of the treatment and what does this include?What would be the costs of emergency treatment, if needed, should a complication arise?
First In The Nation Fda
A Phase II clinical trial to assess mesenchymal adult stem cells as a disease-modifying therapy for Parkinsons disease has been launched at The University of Texas Health Science Center at Houston .
Studies have shown mesenchymal stem cells can migrate to the sites of injury and respond to the environment by secreting several anti-inflammatory and growth factor molecules that can restore tissue equilibrium and disrupt neuronal death, said Mya C. Schiess, MD, professor in the Department of Neurology and director and founder of the movement disorder subspecialty clinic and fellowship program of McGovern Medical School at UTHealth. The stem cells interact directly with the immune cells, leading to an anti-inflammatory state that allows a restorative process to take place.
Safety and tolerability results, assessed on a previous trial, were recently published in the journal Movement Disorders. The Phase I study showed that there were no serious adverse reactions related to the stem cell infusion and no immunological reactions to the cells, which come from the bone marrow of a healthy adult donor. The study enrolled 20 patients with mild to moderate disease, who were infused with one of four different dosages and monitored for a year. Additionally, researchers reported a reduction in peripheral inflammatory markers and a reduction in motor symptoms.
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Why Is Stem Cells Treatment Better Than Conventional Treatment Approach For Treating Parkinsons
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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Mesenchymal Stem Cell Therapies For Neurodegenerative Diseases
While there have been significant advances in the symptomatic management of these diseases that improve quality of life and at times survival, the available medications likely only slow the progression of neuronal death by a few months. The idea of using cell therapy to treat neurodegenerative diseases has been around for decades, most notably in Parkinson’s Disease where a variety of cell transplant investigations have been performed with success.
According to a recent study conducted by Nathan P. Staff et al,
“The precise mechanism by which MSCs may exert beneficial effects in neurological disease is still being elucidated, but it appears that multiple different mechanisms may contribute. First, MSCs have been shown to secrete neurotrophic growth factors, including glial cell-derived neurotrophic factor , vascular endothelial growth factor, and brain-derived neurotrophic factor ,which can be further enhanced under specific culture conditions.Neurotrophic growth factors have been shown to improve neuronal survival in a number of preclinical models of neuron injury, including ALS, PD, and MSA transgenic animalsand nerve injury models. â Second, MSCs strongly modulate the immune system and can aid wound healing, and this mechanism has been exploited in disorders such as graft versus host disease and Crohnâs disease. From a neurodegenerative perspective, it has become increasingly recognized that neuroinflammation plays a significant pathomechanistic role.”
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Giving Stem Cells Outside Of The Brain
There are a number of trials looking that the potential of using different types of adult stem cells for Parkinsons happening all over the world. One example is a phase 1/2 trial based in Texas that started in 2015. The study is using stem cells collected from bone marrow, and aims to recruit 20 participants to see if injection of these cells into the blood is safe. It will also collect results on if this type of therapy can improve movement symptoms of Parkinsons, among other measures.
Another study worth note, although not for its scientific merit, is taking a slightly different tack to getting stem cell into the body. In a rather ambitious phase 2/3 trial happening in China, researchers will attempt to give neural stem cells through the nasal track of 12 participants to see if it can cause Parkinsons to go into remission. Personally I dont hold out much hope for the success of this particular trial.
Potential of this type of therapy: Stem cells produce a range of protective factors that could help to protect brain cells and slow the progression of Parkinsons. The pros of this technique are that various types of adult stem cells such as those from bone marrow are easily accessible and the therapy doesnt involve brain surgery so would be less invasive than other therapies in this post. The cons are that these cells will be unable to get into the brain, and the lack of proximity could hamper their effectiveness.
What Will The Next Generation Of Clinical Trials Focus On
There are many symptoms of Parkinsons disease. Theyre often rated using the Unified Parkinsons Disease Rating Scale or the Movement Disorder Societys updated revision of that scale, the MDS-UPDRS.
Clinical trials today are generally looking to significantly improve UPDRS or MDS-UPDRS scores for people with Parkinsons disease.
Some trials are testing new delivery methods, such as intravenous infusion or topical applications. Others are looking to determine the safest number of effective doses. And other trials are measuring overall safety while using new medical devices in stem cell therapy.
This is an active area of research. Future trials will help narrow down the most safe and effective approach to stem cell therapy for Parkinsons disease.
Each phase adds more participants, with the first phase usually limited to a few dozen people and several thousand in the third phase. The purpose is to test the treatments safety and effectiveness.
Clinical trials testing stem cell therapy for Parkinsons disease are still in the early phases. If the current trials are successful, it will likely still be 4 to 8 years before this treatment is widely available.
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Lifestyle Factors And Parkinsons Disease Risk In A Rural New England Case
Angeline S. AndrewAcademic Editor: Received
Abstract
Introduction. Parkinsons disease is an age-related neurodegenerative disease likely caused by complex interactions between genetic and environmental risk factors. Exposure to pesticides, toxic metals, solvents, and history of traumatic brain injury have been implicated as environmental risk factors for PD, underscoring the importance of identifying risk factors associated with PD across different communities. Methods. We conducted a questionnaire-based case-control study in a rural area on the New Hampshire/Vermont border, enrolling PD patients and age- and sex-matched controls from the general population between 2017 and 2020. We assessed frequent participation in a variety of recreational and occupational activities and surveyed potential chemical exposures. Results. Suffering from head trauma or a concussion prior to diagnosis was associated with a fourfold increased risk of PD. Adjustment for head trauma negated any risk of participation in strenuous athletic activities. We observed a 2.7-fold increased risk of PD associated with activities involving lead .. Implicating these factors in PD risk favors public health efforts in exposure mitigation while also motivating future work mechanisms and intervention opportunities.
1. Introduction
What Are The Symptoms Of Parkinson’s Disease
Parkinson’s DIsease can include a variety of symptoms that vary in severity and type amongst the affected population. Early signs of the condition can sometimes go unnoticed but as the disease progresses one can expect these symptoms:
- Difficulty speaking
- Difficulty writing
- Loss of automatic movements
- Slowed overall movement
- Muscle stiffness
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What Causes Parkinson’s Disease
Parkinson’s Disease is caused by a loss of nerve cells in the brain. This loss of nerve cells within the brain results in a reduced amount of dopamine being created which acts as a messenger between the parts of your brain that control voluntary and involuntary movement. Therefore without that vital connection, your brain starts losing the ability to effectively control movement. Currently, it is unknown what causes the deterioration of nerve cells associated with Parkinson’s Disease . Currently, it is believed that both environmental factors, as well as genetic factors, may play a role in the loss of nerve cells.
Parkinson’s Disease is a lifelong condition that can greatly impair the ability of one’s daily functions. Traditional treatments only address the symptoms of the condition, but researchers are excited about the possibilities of certain gene therapies and stem cell therapy, which may have the ability to reverse damage and halt the progression of the disease.
Application And Molecular Mechanisms Of Neural Stem Cell
Keywords:Neural stem cells, Exosomes, Nervous system diseases, Non-cellular therapy, Regenerative Medicine
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
Keywords:Neural stem cells, Exosomes, Nervous system diseases, Non-cellular therapy, Regenerative Medicine
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
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The Braak Staging Of Parkinsons Disease The Spreading Hypothesis The Search For Prodromal Stages Of Parkinsons Disease: Advantages And Limitations
Shortly after the discovery that a mutation of alpha-synuclein causes PD, alpha-synuclein aggregates were identified in the Lewy bodies in the post-mortem SN samples of patients with idiopathic PD. Therefore, the majority of patients with idiopathic PD are now considered to suffer from an alpha-synucleinopathy. Based on the distribution of these Lewy bodies in the nervous system, Braaket al. postulated that most likely PDas it is defined with its motor symptoms by the neurologistis a late-stage phenotype of a disease which has been going on for decades.
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Well Be Watching Progress Closely
Claire Bale, Head of Research Communications at Parkinsons UK, said:
Were encouraged to hear that approval has been given to do the first ever trial for stem cell treatment in people with Parkinsons.
Stem cells carry real hope as a future treatment for the 127,000 people living with the condition in the UK. Parkinsons UK has invested more than £3 million in cutting edge stem cell research to help develop new and better treatments for Parkinsons, faster.
With all clinical trials, ensuring that the treatment is safe and effective is paramount and along with the international research community we will be watching the progress of the trial very closely.
If successful this could be the beginning to further, much larger studies with stem cells taking us closer to a new potential treatment for Parkinsons.
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