How Do Mesenchymal Stem Cells Work In The Body
Mesenchymal stem cells utilize their self-renewal, immunomodulatory, anti-inflammatory, signaling, and differentiation properties to influence positive change within the body. Mesenchymal stem cells also have the capacity to self-renew by dividing and developing into multiple specialized cell types present in a specific tissue or organ. Mesenchymal stem cells are adult stem cells, meaning they present no ethical concerns, MSCs are not sourced from embryonic material.
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.
New Protocols Extend Therapeutic Benefits Of Deep Brain Stimulation
- Date:
- Carnegie Mellon University
- Summary:
- Researchers have found a way to make deep brain stimulation more precise, resulting in therapeutic effects that outlast what is currently available. The work will significantly advance the study of Parkinson’s disease.
Researchers from Carnegie Mellon University have found a way to make deep brain stimulation more precise, resulting in therapeutic effects that outlast what is currently available. The work, led by Aryn Gittis and colleagues in CMU’s Gittis Lab, will significantly advance the study of Parkinson’s disease.
DBS allows researchers and doctors to use thin electrodes implanted in the brain to send electrical signals to the part of the brain that controls movement. It is a proven way to help control unwanted movement in the body, but patients must receive continuous electrical stimulation to get relief from their symptoms. If the stimulator is turned off, the symptoms return immediately.
Gittis, an associate professor of biological sciences in the Mellon College of Science and faculty in theNeuroscience Institute, said that the new research could change that.
“By finding a way to intervene that has long-lasting effects, our hope is to greatly reduce stimulation time, therefore minimizing side effects and prolonging battery life of implants.”
Teresa Spix, the first author of the paper, said that while there are many strong theories, scientists do not yet fully understand why DBS works.
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Medication For Parkinsons Disease
Once the doctor diagnoses Parkinsons disease, the next decision is whether a patient should receive medication, which depends on the following:
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The degree of functional impairment
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The degree of cognitive impairment
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Ability to tolerate antiparkinsonian medication
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The advice of the attending doctor
No two patients react the same way to a given drug, therefore, it takes time and patience to find an appropriate medication and dosage to alleviate symptoms.
Therapeutic And Formalized Pattern Exercises
The SPARX study enrolled 128 de novo patients and compared high- and moderate-intensity treadmill exercises with a wait-list control group. After six month of 3 days per week exercise, the results showed that the high-intensity group, who exercised at 80 to 85% maximum heart rate, had less change in motor symptoms compared with the usual care group9898. Schenkman M, Moore CG, Kohrt WM, Hall DA, Delitto A, Comella CL, et al. Effect of high-intensity treadmill exercise on motor symptoms in patients with de novo Parkinson disease: a phase 2 randomized clinical trial. JAMA Neurol. 2018 Feb 1 75:219-26. https://doi.org/10.1001/jamaneurol.2017.3517 . The Park-in-shape trial , a home-based study, recruited 130 PD patients in Hoehn & Yahr stage 2 who were randomized either to exercise on a stationary cycle or stretching at least three times per week. After the 6-month program, the MDS-UPDRS motor score change was smaller in the aerobic group, resulting in a between-group adjusted mean difference of 4.2 points favoring the cycling group9999. Van der Kolk NM, de Vries NM, Kessels RPC, Joosten H, Zwinderman AH, Post B, et al. Effectiveness of home-based and remotely supervised aerobic exercise in Parkinsons disease: a double-blind, randomised controlled trial. Lancet Neurol. 2019 Nov 1 18:P998-1008. https://doi.org/10.1016/S1474-442230285-6 .
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Stem Cell Therapy For Parkinson’s Disease
Stem cell therapy may have the benefit of replacing and repairing damaged dopamine-producing nerve cells within the brain. This has already been found in a study conducted by Neelam K.Venkataramana and colleagues. Seven PD patients aged 22 to 62 years with a mean duration of disease 14.7 ± 7.56 years were enrolled to participate in the prospective, uncontrolled, pilot study of single-dose, unilateral transplantation of autologous bone-marrow-derived mesenchymal stem cells . Patients were followed up for 36 months post-transplant, 3 of the 7 patients showed significant improvement in their Unified Parkinson’s Disease Rating Scale of 38%.
According to Medical News Today “Currently, the most common therapy uses the drug levodopa to stimulate dopamine production in certain neurons associated with motor skills. These dopaminergic neurons are situated in the nigrostriatal pathway which is a brain circuit that connects neurons in the substantia nigra pars compacta with the dorsal striatum. However, levodopa has a wide array of side effects, from physiological to psychological ones. Also, in the long-term, the benefits of such dopamine-regulating drugs are limited. So, scientists must come up with more effective strategies for repairing the brain damage that Parkinson’s disease causes.”
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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Top Ways To Treat Parkinsons Disease
This content was developed in partnership with the Parkinsons Foundation.
Every person living with Parkinsons disease experiences symptoms, disease progression and treatments that are unique to them. There is no single treatment plan that works for everyone.
The most common way to treat and manage PD symptoms include medications, exercise, rehabilitation therapies and surgical procedures. Treatment plans should be tailored to respond to an individuals symptoms and personal circumstances. While there is currently no cure for PD, the goals of treatment are to minimize symptoms and improve overall quality of life.
Over The Counter & Complementary Therapies
People with Parkinsons who seek relief from their symptoms may decide to explore complementary therapies, which can support or complement traditional medicine. While there are many kinds of complementary medicine, this section focuses on herbs, vitamins and supplements.
Page reviewed by Dr. Chauncey Spears, Clinical Assistant Professor and Dr. Amelia Heston, Movement Disorders Fellow at the University of Michigan.
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When To Start Treatment
Deciding when to start drug therapy for Parkinsons disease should be individually tailored to a patients symptoms, circumstances and comorbidities. Treatment is indicated when symptoms impact on quality of life. When treatment is needed there is no evidence to support undue delay because of concerns about levodopa toxicity or the development of treatment resistance.3 The aim is to control symptoms and maintain an on state.
Some drugs with good symptomatic benefit are speculated to have a role in neuroprotection and some specialists advocate their use from the time of diagnosis.4 Delayed start trials have been used to try and differentiate symptomatic from disease-modifying effects. A recent delayed start study of rasagiline, a monoamine oxidase B inhibitor, in treatment-naïve patients with mild Parkinsons disease showed a small benefit in the low-dose treatment group. This was not seen with the 2 mg dose and a clear explanation for this has not been established.5 Further studies are needed before such treatments are considered truly disease modifying. Until a drug is unequivocally proven to slow disease progression, the time to commence treatment will remain contentious.
Parkinsons Disease Treatment Guidelines
An update of the Parkinsons Disease treatmentGuidelines was commissioned by the European Academy of Neurology and the European section of the Movement Disorder Society. Although these treatments are initiated usually in specialized centers, the general neurologist should know the therapies and their place in the treatment pathway.
Grading of Recommendations Assessment, Development, and Evaluation methodology was used to assess the spectrum of approved interventions including deep brain stimulation or brain lesioning with different techniques . Continuous delivery of medication subcutaneously or through percutaneous ileostomy ) was also included. Changes in motor features, health-related quality of life , adverse effects, and further outcome parameters were evaluated. Recommendations were based on high-class evidence and graded in three gradations. If only lower class evidence was available but the topic was felt to be of high importance, a clinical consensus of the guideline task force was gathered.
Evidence for invasive therapies in PD is heterogeneous. Only some of these therapies have a strong scientific basis 1)2).
European Academy of Neurology/Movement Disorder Society-European Section Guidelines on Pallidotomy for Parkinsons Disease 3).
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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.”
Restoration Of Dopaminergic Deficits
Treatment of many of the motor symptoms of PD can be achieved through restoration of striatal dopaminergic tone. This may be accomplished through targeted delivery of dopamine-producing cells, or the use of viruses to deliver genes encoding the enzymes required for dopamine biosynthesis into the striatum. Targeting these regenerative treatments to the striatum, the site of greatest dopamine loss in PD, would minimize the off-target effects seen with oral dopamine-replacement.
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Brain Connectomic Studies And Improved Precision Of Neuromodulation Targets
The process of altering brain function through direct manipulation of neural activity has long been used to treat patients with neuropsychiatric disorders and deep brain stimulation has provided clinical benefit to more than 150 000 patients with PD, dystonia and essential tremor . Apart from the conventional application in advanced PD, DBS has also been suggested to exert disease-modifying traits . In multiple preclinical studies on rat models, chronic STN electrical stimulation was shown to result in preservation of SNpc dopaminergic neurons and an increase of brain-derived neurotrophic factors followed by activation of the tropomyosin receptor kinase type B receptor signaling in the nigrostriatal system . Although preclinical experiments suggest potential neuroprotective effects of DBS, results from clinical studies have shown that dopaminergic neuron degeneration remains unaltered , and -syn burden is not reduced in PD patients treated with DBS .
Focused ultrasound as a newly developed neuromodulation technique
Repetitive transcranial magnetic stimulation
Few studies have investigated the effect of rTMS on levodopa-induced dyskinesias, showing only short-lasting or no beneficial effect.
What The Experiments Showed
Initially, the researchers tested the nanobody on mouse brain tissue in vitro. They found that PFFNB2 could bind to aggregates of alpha-synuclein, but could not prevent the formation of clumps.
Further experiments revealed that the nanobody could bind to and disrupt fibrils of alpha-synuclein that had already formed, destabilizing the misshapen proteins.
The researchers then tested this in live mice and found that the nanobody prevented alpha-synuclein from spreading to the cortex of the brain. The cortex is the largest part of the brain and is responsible for most higher brain functions.
Dr. Petrossian explained for MNT that he results showed that they were able to specifically target the preformed fibrils of alpha-synuclein in cell and mouse models, that they were able to reduce the clumping of alpha-synuclein in cell models, and they were able to reduce alpha-synuclein pathology in mouse models.
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Risk Factors For Parkinsons Disease
The cause of Parkinsons remains unknown, but several factors can contribute to its development, including a family history of the disease. Men are more likely to develop Parkinsons, and most people develop the disease around age 60 or older, although in 10% of cases it can begin as early as age 40.
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Amneal Tests A New Formulation
AmnealPharmaceuticals plans to report Phase III safety results for IPX-203, a reformulation of the common generic PD treatment combination of carbidopa and levodopa that could reduce symptom fluctuations. The company said the Phase III, open-label extension study will have results available by the end of the second quarter of 2022.
CD/LD can lead to troughs and spikes of plasma levels that generate side-effects like dyskinesia, Kordower explains. A new extended-release version of CD/LD could smooth out these drops, he notes.
If approved, IPX-203 will join several other marketed reformulations of CD/LD. Amneals own extended-release capsule Rytary, Schwarz Pharmas orally disintegrating tablet Parcopa, and AbbVie’s enteral suspension Duopa all have FDA approval in PD. A GlobalData consensus forecasts pegs peak IPX-203 sales at $127 million in 2028.
In a separate, placebo-controlled Phase III trial , IPX-203 resulted in 0.53 more hours of ON time than immediate-release CD/LD after seven weeks . Earlier, a six-week Phase II trial of IPX-203 reported no serious treatment-emergent adverse events among the 26 patients enrolled. Experts say the long-term safety data will be key in determining IPX-203s place among CD/LD formulations.
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The First Participant Has Been Recruited To A Pioneering Clinical Trial Which Is Testing A New Drug Called Nlx
Parkinsons disease is a condition in which parts of the brain become progressively damaged over many years. The main three symptoms manifest themselves in involuntary shaking of parts of the body, slow movement, and stiff, inflexible muscles.
People with Parkinsons struggle to make enough dopamine. They take medications like levodopa which help their struggling dopamine cells to make more of this chemical and helps improve symptoms, especially difficulty in movement.
However, serotonin cells also get involved in using levodopa to make and release dopamine, but they do so in an erratic manner. This uncontrolled release of dopamine leads to distressing uncontrollable movements called dyskinesia.
The trial is led by researchers at the Karolinska Institute in Stockholm and at 4 other sites in Sweden. A total of 24 participants will be involved, with 16 receiving NLX-112 and the remainder an inactive pill for comparison.
Parkinsons Disease Treatment Options
Parkinsons is incurable, but the symptoms can be managed as the disease progresses. Initially, your doctor may recommend lifestyle changes, such as ongoing aerobic exercise, healthy diet, and advice for avoiding falls.
Medication
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Carbidopa-levodopa : Sometimes simply called Levodopa, is the most effective Parkinsons disease medication and has been since its breakthrough in the late 1960s. It is an effective first-line treatment for Parkinsons and comes in many formulations, including slow- and extended-release pills, and infusions. It works by introducing a natural chemical to the body which converts into dopamine in the brain. This helps reduce symptoms of stiffness and tremors. The medication does not slow the progression of the disease.
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Catechol O-methyltransferase inhibitors: These pills can boost the effectiveness of carbidopa-levodopa. It helps block the brains dopamine breakdown to help reduce some of the tremors and motor symptoms of Parkinsons.
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Dopamine agonists: This medication mimics the effect of dopamine in the brain and may be used with carbidopa-levodopa. It can be prescribed in the early stages of Parkinsons, and it can lengthen the effectiveness of carbidopa-levodopa.
Innovative surgical options
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Parkinsons Disease Pipeline Offers Promising New Options For Treatment
DelveInsights Parkinsons Disease Pipeline Insight report provides comprehensive insights about 150+ companies and 150+ pipeline drugs in the Parkinsons Disease pipeline landscapes.
Los Angeles, USA, Jan. 17, 2022 Parkinsons Disease Pipeline Offers Promising New Options for Treatment | DelveInsight
DelveInsights Parkinsons Disease Pipeline Insight report provides comprehensive insights about 150+ companies and 150+ pipeline drugs in the Parkinsons Disease pipeline landscapes.
The report comprises Parkinsons Disease pipeline drug profiles, including clinical and non-clinical stage products. It also includes the Parkinsons Disease therapeutics assessment by product type, stage, route of administration, and molecule type and further highlights the inactive Parkinsons Disease pipeline products.
Get an overview of pipeline landscape @ Parkinsons Disease Clinical Trials Analysis
Parkinsons Disease is a progressive disorder caused by degeneration of nerve cells in the part of the brain called the substantia nigra, which controls movement.
· Combination· Mono/Combination
Key Questions regarding Current Parkinsons Disease Treatment Landscape and Emerging Therapies Answered in the Pipeline Report
Exploring Seven Recently Approved Parkinsons Treatments
Remarkably, in the last five years, seven new medications have been approved for the treatment of the motor symptoms of Parkinsons disease , with two approved in 2020. Thats exciting progress! And while it is great to have so many choices, the various options can be confusing so today I will describe these new medications and their uses.
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