Parkinsons Surveys And Clinical Trials
If youd like to be part of early research efforts that are looking into the efficacy of service dogs for those living with Parkinsons, you can take this survey here.
Park Test University of Rochester
LSVT Global and Project Euphonia
BouNDless Phase 3 trial to investigate the efficacy, safety, and tolerability of ND0612, a continuous subcutaneous levodopa/carbidopa delivery system in comparison to oral levodopa/carbidopa in people with Parkinsons experiencing motor fluctuations
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Conformational Transition Of Inhibited
Component #2 A Neuroprotective Agent
Once a drug or a treatment has been determined to slow down the progression of Parkinsons, it will be necessary to protect the remaining cells and provide a nurturing environment for the third part of the cure .
But there has been the hint of a potential neuroprotective effect in one class of drugs for Parkinsons: GLP-1R agonists.
Neuroprotective approach: GLP-1R agonists
Sample Size And Statistical Analysis
We targeted a sample size of 25 per group, with assumed 7% dropouts unrelated to agent tolerability. This sample size provided 80% power to detect a difference of 30% in the proportion of subjects tolerating mannitol relative to placebo , assuming the placebo group will have more than 90% tolerability.
Efficacy measures, calculated only for those patients who completed the treatment originally allocated, were not powered to detect statistically significant differences, but rather to be used for designing future efficacy studies with the maximal tolerable dose of mannitol that will be defined in this study. The targeted sample size , however, would have enabled us to detect inter-group differences of 20% in the mean of continuous variables with 80% power in 2-sided t-test with alpha < 0.05 in case the intra-group standard deviation would be 24%. Differences between groups were assessed using two-sided Wilcoxon rank sum test.
The COVID-19 pandemic in 2020 dramatically slowed recruitment rate in the 3rd year of the clinical trial and led to the decision of earlier trial termination.
The Investigation In Mice
In their recent study paper, the scientists refer to research suggesting that neurotrophic factors molecules that help neurons survive and thrive could, in theory, restore the function of neurons that produce dopamine. However, the clinical benefit of these factors had yet to be proven.
The team focused on bone morphogenetic proteins 5 and 7 . They had previously shown that BMP5/7 has an important role in dopamine-producing neurons in mice.
In the latest study, the scientists wanted to see whether BMP5/7 could protect the neurons of mice against the damaging effects of misfolded alpha-synuclein proteins.
To do this, they injected one group of mice with a viral vector that caused misfolded alpha-synuclein proteins to form in their brains. They used other mice as a control group. The scientists then injected the mice with the BMP5/7 protein.
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Mannitol Balance The Sweetly Natural Solution
Mannitol Balance is proud to be part of an exciting breakthrough in 21 st century Medicine, offering an innovative and natural solution to help fight the debilitating effects of the disease.
For people who suffer from Parkinsons Disease, Mannitol Balance offers a ground-breaking alternative to conventional treatments.
Roles Of Osmolytes In Protein Folding And Aggregation In Cells And Their Biotechnological Applications
names Mannitol as one of these bio-protective substances.
“Nature has selected osmolytes to protect intracellular macromolecules exposed to denaturing conditions and stabilize proteins. Osmolytes are small naturally occurring compounds that act as ‘chemical chaperones’ under changing environmental conditions and in disease states, and are present in microorganisms, animals, and plants. In the intracellular environment osmolytes naturally accumulate at high concentrations when cells/tissues are exposed to stressful conditions, which is important because protein aggregation, misfolding, and destabilization underlie the pathogenesis of several life-threatening neurodegenerative disorders. The ‘chaperone’ abilities of osmolytes suggests they may be therapeutically used for the treatment of several diseases associated with protein misfolding , and their abilities to protect proteins against stresses”
Specifically, the researchers say about Mannitol:
“Mannitol protects thiol-regulated enzymes such as thioredoxin, phosphoribulokinase, ferredoxin and glutathione from inactivation by ROS quenches hydroxyl radicals and protects the enzymes inactivation by reactive oxygen species “
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Retrospective Power Calculation For Future Trials
PD patients who buy and consume oral mannitol frequently report improvement of their sense of smell. In our small study no such effect was observed . Based on these results, a future study aiming to demonstrate an improvement of at least 1 point on the B-SIT test, with a power of 80% and a significance level of 5% in a one-sided paired t-test, would require a sample size of at least 32 subjects on mannitol.
One More Stone To Unturn
I have yet to see anything definitive offered by pharmaceutical companies to cure or slow the progression of Parkinsons. Most of what is newly available or on the horizon are drugs to treat symptoms. Based on feedback from the CliniCrowd results, mannitol looks like it might have promise, both in terms of relieving symptoms and possibly slowing progression.
Rather than wait for the trial to end, and after I consult with my neurologist, I may take mannitol to see what it might do for me. Hopefully, in six months, I can report some positive results.
Keep in mind this column is not meant as medical advice, but rather a source of information. Discuss any treatment options with your healthcare providers before trying something new.
The pessimist complains about the wind the optimist expects it to change the realist adjusts the sails. William Arthur Ward
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Sweet Success Study Backs Mannitol For Parkinsons Disease
The study, published in the Journal of Biological Chemistry, suggests that the artificial sweetener could be a novel way to reduce the risk of developing Parkinson’s and other neurodegenerative diseases because it prevents clumps of the protein alpha-synuclein forming in the brain a process that is characteristic of Parkinson’s disease.
Led by Professors Ehud Gazit and Daniel Segal from Tel Aviv University, Israel, the research team found that mannitol was among the most effective agents in preventing aggregation of the protein in test tubes before testing its ability to block formation in fruit flies and mice.
Study details
Gazit and Segal first identified the structural characteristics that lead to the development of clumps of alpha-synuclein, before the team began to hunt for a compound that could inhibit the proteins’ ability to bind together.
Then, in order to test the capabilities of the sweetener in the living brain, the team turned to transgenic fruit flies engineered to carry the human gene for alpha-synuclein.
They used a ‘climbing assay’ test in which the ability of flies to climb the walls of a test tube indicates their locomotive capability. Initially 72% of normal flies were able to climb up the test tube, compared to only 38% of the genetically-altered flies. However when the team then added mannitol to the food of the genetically-altered flies for 27 days and repeated the experiment 70% of the flies could complete the test.
Real Life Experiences Of People With Pd
Andy Butler, who I consider to be a world authority on Parkinson’s and the man behind the Parkinson’s People project, writes: “People all over the world with pd take this ! I have met many pwp who have tried this and still take it. Cheap and ready available in almost every where world wide. GIVE IT A GO – IT MAY HELP YOU !”
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Are There Any Other Benefits Of Mp
There is some research in animal and cell models that MP may contain other ingredients besides levodopa which have anti-oxidant properties or other neuroprotective effects. More research is necessary to determine if this is clinically meaningful for people with PD.
It must be noted that there are parts of the world in which carbidopa/levodopa tablets are not available or are unaffordable. In these areas, increasing access to levodopa from plant sources may be very beneficial for the PD population.
Coconut Oil And Parkinson Disease
In recent years, many people who suffer from PD said that regular consumption of pure coconut oil significantly improved their symptoms. Studies support their claim: it seems that coconut oil contains glucose and other ingredients the brain uses as fuel after PD caused their deterioration.
How to Use Coconut Oil for PD:
Coconut oil can be found in almost every supermarket. It can be cooked or consumed as-is.
Number 1:
Mannitol Powder
A new Parkinsons treatment , while all the natural remedies to Parkinsons Disease mentioned above have their benefits, Mannitol is a whole different level. Mannitol is a sugar alcohol . This natural low-calorie sweetener can be produced from various kinds of fruits, leaves, and other natural substances. You probably know it as the thin powder that covers some chewing gums is mannitol.
What is the connection between this natural sweetener to treating PD symptoms?
How Does Mannitol Powder Work?
Testing The Neuroprotective Effects Of Mannitol In A C Elegans Model Of Parkinsons Disease
Talya Scott, 23, has a major in Neuroscience and minors in Public Health and Chemistry. Her time spent working in a nursing home and interest in medicine led her to pursue a research project testing a potential treatment for Parkinsons Disease in a C. elegans model. After completing this summer research project, she plans to continue her research as an SYE to further expand her own and the scientific communitys understanding of this disease.
Advisor
Parkinsons Disease is the second most common neurodegenerative disorder resulting in symptoms such as resting tremors, muscle rigidity, and impaired balance. Familial PD has been found to result from mutations in the gene for the protein -synuclein and accumulation of -synuclein is found in familial and sporadic cases of PD. Prior research found that the chemical mannitol has a neuroprotective effect in a Drosophila model of PD. For my research project, I used a C. elegans model of PD, which is genetically modified to produce human -synuclein, to test the impact of mannitol as a potential PD treatment. C. elegans is a nematode roundworm that works well as a model organism for addressing neurobiological questions because of its well understood nervous system and genome. Throughout the course of my research, I conducted preliminary research and created a research design to measure behavioral defects and aggregation of -synuclein in the C. elegans. I will be using this research design to collect data as an SYE.
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In The Clinical Trial
Although CliniCrowds published results may not be enough to win over skeptics, the project has succeeded in sparking one clinical trial aimed at more rigorously investigating mannitols potential benefit in Parkinsons.
Based on anecdotal evidence from CliniCrowd and other physicians treating Parkinsons cases, David Arkadir, MD, PhD, a physician and neurologist at Hadassah Medical Center in Jerusalem, secured funding for a small Phase 2a trial in 2019.
In 2016, the Israeli government offered grants to physicians studying generic substances that might be medically useful, but had no clear financial benefits. Arkadir and his colleagues submitted a proposal for mannitol and won one of these grants.
His trial consists of about 30 participants, who are assigned randomly to receive either mannitol or dextrose, a similarly sweet sugar that serves as a placebo.
The patients in this trial are followed for 36 weeks, during which the safety and tolerability of mannitol is assessed. As secondary outcomes, they also are collecting data on several clinical features of Parkinsons.
These features include changes in levodopa dosage, the ability to detect scents, and changes in constipation, as well as changes in cognitive and motor symptoms.
Arkadir expects the trial to end in approximately two to three months and hopes to report results sometime in mid-October.
The one risk we run into with a relatively small Phase 2 trial is they often dont replicate in Phase 3, she said.
Parkinson’s Disease And Movement Disorders Center
Our center provides compassionate and timely treatment to patients with movement disorders, such as dystonia, ataxia, essential tremor and similar conditions. But our mission goes beyond patient care excellence. By offering educational events and support groups, we empower patients and caregivers to become better partners in their health.
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Mannitol As A Prebiotic
Mannitol is a type of “diabetic sugar” which has a low glycemic index and is barely absorbed in the body, tending to pass straight through. People with Parkinson’s around the world are finding cumulative benefit with daily use of mannitol as a supplement. Andy Butler of Parkinson’s People, who travels the world talking to PD groups, to seek out and share the best practices of living well with the condition, says “pain and fatigue seem to be helped by mannitol”. No-one really knows why it is working so well for some PwP, but having done the research, but we do know that mannitol is a good prebiotic, as listed in:
Can It Be Used As A Treatment
There is no strong evidence to support that mannitol improves Parkinson’s symptoms, but many swear by it. Mannitol can be bought online as a food supplement, called a nutriment. It is widely available and already being individually tested by many with PD.
People with Parkinson’s can sign up for registries to get mannitol products and have the opportunity to report their findings in various forums supported by manufacturers and suppliers. The self-reports are that people feel better, clearer and improve motor symptoms.
Human clinical studies on the efficacy of mannitol in PD could take many more years to get approved. At this point, there isn’t enough interaction research to anticipate the effect mannitol may have on the absorption of L-dopa and other Parkinson’s disease medications. As always, remember to talk to your doctor before making any changes to your medications or taking any kind of supplement.
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Congo Red Birefringence Of Inhibited
Congo red is known as an amyloid specific dye and exhibits yellow green birefringence upon binding with ordered amyloid structures under cross polarized light . We used it to further validate the effect of the inhibitors on ?-Syn fibrillization. Following incubation of ?-Syn in the absence of inhibitors for 50 h Cong red staining resulted in a clear green-gold or apple-green birefringence, indicating the presence of amyloid fibrils in the sample . Some green-gold birefringence was observed in ?-Syn samples that were incubated with 1:1 molar ratio of the inhibitors, indicating that 1:1 molar ratio was not sufficient for inhibition of ?-Syn fibrillar aggregates, except compound M2N and M3N which were more effective, as observed in morphological analysis by TEM. In contrast, no birefringence was observed when ?-Syn was treated with 1:5 molar ratio of all inhibitors tested except in presence of Mannitol . Collectively, the results of ThT, CD, TEM, and Congo red birefringence, indicate that the conjugate molecule M3N was a superior among all tested molecules.
Usual Adult Dose For Cerebral Edema
0.25 to 2 g/kg as a 15 to 20% solution IV over at least 30 min administered not more frequently than every 6 to 8 hrs.To yield a satisfactory reduction in intracranial pressure, the osmotic gradient between the blood and cerebrospinal fluid should remain approximately 20 mOsmol.In small & /or debilitated patients 500 mg/kg may be sufficient.
Iron And Dopamine: A Toxic Couple:
Protein Identified That May Help Treat Parkinsons Disease
Scientists have identified a protein that can slow or stop some signs of Parkinsons disease in mice.
The team found that the bone morphogenetic proteins 5 and 7 can have these effects in a mouse model of the disease.
This research, which appears in the journal Brain, may be the first step toward developing a new treatment for Parkinsons disease.
, and the symptoms worsen with time.
Common symptoms include stiffness, difficulty walking, tremors, and trouble with balance and coordination.
The disease can also affect the ability to speak and lead to mood changes, tiredness, and memory loss.
Parkinsons Foundation report that about 1 million people in the United States had the disease in 2020, with about 10 million affected globally.
Despite this prevalence, scientists are still unsure why Parkinsons disease affects some people and not others, and there is currently no cure.
The National Institute on Aging note that some cases of Parkinsons disease seem to be hereditary. In other words, the disease can emerge in different generations of a family but for many people with the disease, there appears to be no family history.
Researchers believe that multiple factors may affect a persons risk, including genetics, exposure to environmental toxins, and age.
Since there is currently no cure for Parkinsons disease, treatments typically focus on alleviating its symptoms.
The disease
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Mannitol Powder: A Promising Parkinsons New Treatment
Apparently, pharmaceutical companies dont want people with Parkinsons to know that there is a natural, cheaper and effective way to treat the disease.There are approximately one million Americans with Parkinsons Disease, with additional 10 million worldwide. They all suffer daily from PDs symptoms: slow movement, limbs stiffness, uncontrollable tremors, cognitive functions decline, speech problems, and more.
Parkinsons Disease hurts the living quality of those who have it. Still, almost no one heard of the Mannitol powder breakthrough of 2013. What was this breakthrough? How can it change the lives of the millions who suffer from Parkinsons? And why dont the pharmaceutical companies want you to know about Parkinsons Disease New Treatment?