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Why is there still no cure in Parkinson’s disease?

Despite significant investments in research to fight Parkinson’s disease, no treatment targeting regeneration of dopaminergic neurons, or at least slowing the progression of the disease, has been authorized on the market. Promising announcements of the pharmaceutical research laboratories are numerous, but a growing number of patients are asking the question: why is it always for tomorrow, and then the day after tomorrow …?

Live Better Parkinson’s has tried to bring some answers to this legitimate question.

A medical culture of symptoms

The essential reason indeed lies in our medical culture of treating a disease. In a study by Meissner WG et al. of 2011 “Priorities in Parkinson disease Research” published in the scientific journal “Nat Rev Drug Discovery”, he points out that among dozens of drugs on the market in the care of patients with Parkinson’s disease, NONE targets neuroprotection. So no strategy has been developed to stop or slow down the progression of the disease.

Although symptoms can be improved through dopamine replacement strategies, there is an urgent need to reorient current research. The strategy should target treatments producing neuroprotective and/or disease-modifying effects so that patients can hope to see the neurodegenerative process slow down.

All neurodegenerative diseases including Parkinson’s, are complex pathologies

Even today, experts do not entirely agree on the pathogenesis of Parkinson’s. So, how do you fight an enemy if you do not know, at least partially, why he can emerge and settle in a patient?
At present, experts agree that several phenomena are always present and at the origin of Parkinson’s disease. All neurodegenerative diseases have common factors such as oxidation, neuroinflammation, mitochondrial dysfunction (cell power plants), genetic damage (protein misfolding and aggregation), among others.

The neuro-degenerative diseases of which Parkinson is like a bottomless pit or a bathtub with multiple holes. If we want to close only one hole hoping to see the bathtub stop emptying, we may not be able to see a very significant slowdown. It would be appropriate to simultaneously plug several holes, at least all major ones if we want to observe a significant slowdown of leaking.

Thus, to hope to impact significantly the process of Parkinson’s disease, it should be considered one or more drugs to overcome all the underlying problems. And of course, drugs without side effects …

Note that an approach is currently being tried to regenerate neurons and synapses, among other approaches in the therapy of stem cells (pluripotent cells) that can generate neurons (neurogenesis).

Prevention is better than cure

We are far from the traditional approach of Chinese medicine which provided that the doctor was paid as long as his patients were in good health. He had every interest in having his patients go well because it was only in this situation that he was paid. Our system is just reversed because it is based on the treatment of diseases. It also gives high priority to the consequences of the disease, trying to reduce the symptoms, often to the detriment of causes.

Recently, with uncontrolled spending and NHS on the brink of collapse, governments, FDA and NHS are focusing more on a highly personalized and preventive approach.

The number of biomarkers to detect people at risk or the first warning signs of disease is proof of this reorientation. FDA is strongly focussing on personalized medicine including biomarkers.

A toxic environment

Experts estimate that in only 5 to 15% of cases, the disease has an inherited genetic origin. Why are Parkinson’s statistics soaring exponentially?

A series of explanations are put forward to try to understand this phenomenon which takes proportions of a pandemic: An aging population with a longer lifespan, an increase of the stress, pollution, the “junk food” as well as the accumulation of toxic products for the body, would be responsible.

It is true that pesticides, but also household chemicals, heavy metals, and other toxic agents are suspected to be responsible for 85-95% of the remaining factors that would cause Parkinson’s disease. It should also be noted that the average age is becoming lower and it is not uncommon to see people under fifty affected by the disease.

What perspectives?

Prevention, with early biomarkers, will play a significant role in the apprehension of this terrible disease. A healthy lifestyle can certainly also help slow down the disease process. Many studies testify to this.

Stem cell therapies are also exciting because they have the objective of regenerating neurons, although this will remain expensive and complicated processes.

Neurostimulation is also making progress in reducing symptoms.

Other approaches are on the horizon. We can mention for example French biotech that develops a molecule that has demonstrated powerful neuroprotective effects in preclinical models and simultaneously targets the major processes involved in the pathogenesis of the disease.

Also worth mentioning are dietary supplements, some of which show very interesting neuroprotective effects, with preclinical and clinical studies to support it.

We hope that these different approaches and therapies will be accessible quickly, so that people who have suffered from Parkinson’s for years or decades may see their quality of life improve.

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Breakthrough in Parkinson’s disease: A bioproduct, rich in L-dopa, neuroprotective and without side effects

Finally! A European team specialized in neurodegenerative diseases has published preclinical and clinical studies on a food supplement of natural origin, launched on the market under the name AtremoPlus.
The exceptional results of the studies demonstrate that the bioproduct significantly increases the levels of dopamine and norepinephrine in the body and at the same time improves the symptoms of the disease. The report shows that no undesirable side effects have been noticed during the clinical trial. The studies also reveal a robust neuroprotective potential that could help in the field of prevention and enhance slowing down the disease progression. Is this a significant step forward in the fight against Parkinson’s disease?

Origins of Parkinson’s disease

Parkinson’s disease has its roots in the progressive degeneration of dopaminergic neurons. The primary symptoms are well known: stiffness, tremors, slow movements, and depression. In addition, there is a multitude of other symptoms that make this disease extraordinarily debilitating and painful to live on a daily basis. It is physically, psychologically and socially exhausting for patients as well as for the families and caregivers.

Dopaminergic neurons receive the L-dopa and convert it into dopamine. This process is possible as long as there are enough dopaminergic neurons to ensure the ability of synthesis, storage and gradual release of dopamine. Dopamine is a neurotransmitter that plays a key modulatory role in a multitude of psychomotor functions. It intervenes in the coordination of movements, learning, motivation and the rewarding process and other essential functions. The dopaminergic neurons decrease naturally and gradually with age in all populations. However, in people with Parkinson’s disease, this degeneration occurs more quickly. The hereditary phenomenon seems to play a minor role (about 10%). Moreover, even if it is not yet fully understood, exposure to toxic agents (pesticides, toxins, additives, and others) and pollution in general, combined with inappropriate nutritional habits and a sedentary lifestyle, seem to play a significant role in the development of the disease. When the loss of these dopaminergic neurons reaches the critical threshold of 60 to 80%, the known symptoms of this disease appear gradually.

Decreased effects of synthetic L-dopa over time

To produce dopamine, the body needs its precursor, L-dopa. If the body can not produce enough dopamine because too many of its dopaminergic neurons are destroyed, then the standard treatment is the prescription of synthetic L-Dopa drugs. This disease management works quite well for the majority of the patients during the initial phase of the disease, 3-5 years on average. After this phase, the drugs often have reduced effects, causing “on/off problems” and “Freezing” to patients which are characterized by an involuntary blockage of movements. It is frequently observed that the undesirable effects increase with the progressive increase of the dosage of the drugs. Another symptom very disabling which appears regularly at this more advanced stage of the disease is dyskinesia, characterized by involuntary movements.

Patients are forced to attend helplessly this more or less rapid decline, and often the moral is entirely down by this lack of perspectives. It is even more difficult for PD sufferers to mobilize themselves and fight against the disease as dopamine also plays a crucial role in motivation. Lacking dopamine can cause sadness and depression observed in almost 30% of patients facing Parkinson’s disease.

Research for a natural solution without side effects

Since 2010, a European scientific team has worked on the development of a natural product to provide concrete answers in the fight against Parkinson’s disease. The target was also to include in this development a real prevention strategy and action on slowing down the progression of the disease, mainly absent to this date in the care of patients.

The result of this research is a food supplement, rich in L-dopa of natural origin and very well tolerated. According to the nutritional analysis mentioned in the scientific study, the complex elaboration of the product also allows the extraction and preservation of a multitude of extremely beneficial bio-functional elements a trace levels. Among the variety of components we can mention: omega-3 fatty acid (alpha-linolenic acid), proteins (albumin, glutenin, tyramine), vitamins (Vitamin A, Vitamin C, Vitamin E, Vitamins B1, B2, B3, B5, B6, B9), essential amino acids (aspartic acid, serine, tyrosine, phenylalanine, cysteine and histidine), minerals (manganese, magnesium, phosphorus, iron, zinc, copper, potassium, calcium, sodium and selenium ) and factors (beta-carotenes, quercetins, kaempferol, lecithins, lectins, saponins, alpha-amylase inhibitor, alpha-galactosidase and phytic acid). Many of these compounds are well known to be beneficial in neurodegenerative diseases. This set of natural components has demonstrated excellent results in the studies and a high potential for both the significant symptoms relief in Parkinson’s disease but also on the neuroprotective part to slow the progression of the disease. Since the product is very well tolerated, a real prevention strategy could also be targeted.

Clinical study and possible fields of application of the food supplement

For the clinical study, the participants were divided into two groups: on the one hand, Parkinson’s patients with long-term treatments with classical antiparkinsonian drugs; on the other hand, Parkinson’s patients that had never been treated with antiparkinsonian drugs, and 100% of whom showed dramatic hypodopaminergic state with plasma dopamine levels below 20pg/ml.

The clinical study revealed five significant benefits of the food supplement:

  • The significant increase in dopamine levels in the body thanks to its natural concentration of L-DOPA (20mg/g).
  • The duration of the effects that last up to 12 hours after the intake.
  • Product tolerance: 100% of the participants in the clinical study tolerated the product well without any undesirable side effects.
  • The significant increase in norepinephrine, which plays a crucial role in regulating mood.
  • Possible reduction of doses of antiparkinsonian drugs.

An intake of 5g of the product increases the dopamine levels by at least 200% within 30-60 minutes, with a duration of action of up to 12 hours, at the same time improves the cardinal symptoms of Parkinson’s disease: bradykinesia (slow movements), tremors and hypertonia (rigidity).

Taking into account the efficacy of the bioproduct and the positive results, the authors of the clinical study suggest that this food supplement of natural origin could be a solution to:

  • Reduce the phenomenon of “Wearing off” or “deterioration of the end of dose” (observed mainly in the intermediate and advanced phases).
  • Reduce dyskinesia (intermediate and advanced phases).
  • Help to potentiate the therapeutic effect of conventional antiparkinsonian drugs and delay the phenomenon of “lack of response” by the neuroprotective aspect (from the initial phase to the advanced phase of the disease).
  • At the same time, reduce the short and long-term undesirable side effects of conventional antiparkinsonian drugs (from the initial phase to the advanced phase of the disease).

The study reveals that the co-administration of the food supplement with antiparkinsonian drugs, allows a reduction of thee doses of conventional treatments by 25-50%, with advantageous clinical effects and a reduction of undesirable side effects of these drugs.

Thus, this food supplement would be useful for all phases of Parkinson’s disease (initial, intermediate and advanced). Patients who have significant adverse reactions to usual anti-Parkinson’s treatments from the beginning and cannot use conventional drugs could benefit from the bioproduct as well as those who tolerate better natural products in general.

Selective protection of dopaminergic neurons

Preclinical studies have demonstrated a high potential for the protection of dopaminergic neurons, which helps to slow the progression of the disease. This neuroprotective quality of the food supplement, combined with its excellent tolerance without side effects, suggests that the product has an excellent profile also for its use in the prevention of the disease. It has been demonstrated that the active ingredients contained in the product can selectively protect dopaminergic neurons. This characteristic of the product could indeed be a key in all the phase of Parkinson’s disease. It would preserve the remaining dopaminergic neurons and therefore slow down the process of degeneration.

The bioproduct has already been launched on the market

The conclusions of these scientific studies suggest that the food supplement, which is already on sale on the internet, could contribute to significantly improve the quality of life of patients, considering that patients need solutions and efficient results right now due to their often situation which is often dramatic.

Would it be once more nature that will open us complementary ways solutions by offering us significant advances for a better life quality for those who are concerned by this terrible disease?

In any case, it is exciting to notice that research is targeting the development of natural products again, even if the compounds of nature are not patentable and that consequently, the potential profits are minor compared to the synthetic molecules …

Live better Parkinson


Note:
If you have articles, products, tools, tips, aids, applications or any other thing that can significantly help those affected by Parkinson’s disease, please let us know.

Scientific articles are published and accessible on the websites of the following scientific journals: “Journal of Genomic Medicine and Pharmacogenomics”; “Journal of Nutrition & Food Sciences”; “Clinical & Medical Biochemistry”; “Predictive, Preventive and Personalized Medicine & Molecular Diagnostics”; “Journal of Exploratory Research in Pharmacology”; “International Journal of Molecular Science”; “Current Pharmaceutical Design”.

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Scientific study reveals how Parkinson’s disease appears

The unexpected toxicity of very low doses of neurotoxin (MPTB) in mice has been a key to understand the origin of Parkinson’s disease

This study led by researchers at the University of Bordeaux and at the CNRS in France is certainly an important discovery to understand how Parkinson’s disease appears, that’s to say why dopamine neurons die in advance?

Researchers from the National Centre for scientific research in Bordeaux (France) found on the animal model, that the injection of a neurotoxic product (MPTP) on laboratory mice has substantially the same effects as those found in Parkinson’s disease. This finding supports the hypothesis that Parkinson’s disease origins in environmental factors such as toxins to which patients were exposed in their environment (products used at home, for the garden, the surroundings or at work .)

However, this study raises a key factor, because the problem of this hypothesis of environmental origin of Parkinson’s disease is lack of evidence in the analysis: few toxic substances have been found in the brain of patients with Parkinson. The particularity of this new study is that injected dose into the brains of mice was extremely weak. However, destruction of dopaminergic neurons and motor problems associated were identical between a low dose and a more important dose!

The inability of cells to produce a detoxification mechanism, even in very small doses, could be key explanation in the origin of Parkinson’s disease. This could explain, why there is only a  little presence of these toxins in the brain of Parkinson’s patients.

Life Better Parkinson’s tip:

Avoid the plague all toxic substances (* COPs) as much as you can. Products of our daily lives could be discrete murderers that go unnoticed by corporate irresponsibility, lack of laws, especially scientific studies and lack of knowledge on our side.

* =Cops Persistent Organic Compounds

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Are stem-cell therapies for parkinson’s disease ready for clinical trials?

International consortium suggests caution, as reported in the Journal of Parkinson’s Disease

Amsterdam, NL, March 29, 2016 – As stem cell-based therapies are moving rapidly towards clinical trials, treatments for Parkinson’s Disease (PD), an incurable condition, may be on the horizon. A recent announcement of a Phase I/IIa clinical trial involving transplantation of stem cells into the first human subjects has raised hope among patients and sparked discussions in the research community. In a commentary published in the Journal of Parkinson’s Disease, authors propose five key questions that should be addressed as this trial begins.

News of California-based biotechnology company, International Stem Cell Corporation’s (ISCO) clinical trial spread rapidly through online and print news and social media. Many PD patients and their families have questioned whether they should try to sign up for such a study. “As with many such exiting news items, however, one should also react with caution, especially since the outcome of this trial can affect the development of other stem cell programs moving towards clinical trials,” explained lead author Roger A. Barker, PhD, of the John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, UK.

In the wake of clinical trial announcements from ISCO it is timely to provide insights into how the opportunities provided to PD patients in this and similar trials should be evaluated. Without this, the patient community is left trying to interpret complex scientific issues on its own, and individual patients cannot make informed decisions on whether they should seek to participate in the planned trials or not.

The authors review the clinical transplantation trial in PD planned by ISCO this year in light of the criteria defined by the GForce-PD. This global collaborative initiative aims to define criteria to gauge progress from experimental results towards clinical trials, while ensuring that all steps are conducted to the highest standard and that the trials are not initiated prematurely.

Before any stem-cell-based trial in PD is done, the authors call for discussion of these five key questions:

1. What is being transplanted, and what is the proposed mechanism of action?

2. What are the pre-clinical safety and efficacy data supporting the use of the proposed stem cell product?

3. Can arguments concerning ethics, risk mitigation, or trial logistics outweigh concerns regarding the expected efficacy of the cell and constitute a primary justification for choosing one cell type over another in a clinical trial?

4. What is being claimed regarding the potential therapeutic value of the stem cell-based therapy – better control of symptoms or a cure?

5. What is the regulatory oversight of the trial and is it guided by input from experts in the field?

In this commentary, the authors briefly review how cell-based therapies for PD have evolved and discuss some of the early results, as well as some of the ethical issues concerning fetal stem-cell use. They then elaborate on the five key questions and express some concern that there is missing or incomplete information available from ISCO. In particular, there are concerns that the particular cell types being transplanted may not function as desired, and that supporting safety and efficacy data have not been made public. The consortium also suggests that the length of follow-up in the proposed trial may not be sufficient.

While early claims suggesting the possibility of a “cure” had been made, ISCO has now taken a more measured position regarding potential benefits. Nevertheless, the authors caution that exaggerated claims are all too common, given the regulatory hurdles, commercial interests, and personal ambitions of the participants in early-stage clinical trials.

With the reality of the first human clinical trial in patients with PD upon us, co-author and Editor-in-Chief of the Journal of Parkinson’s Disease Patrik Brundin, MD, PhD, Director of the Center for Neurodegenerative Science at Van Andel Research Institute in Grand Rapids, MI, commented, “This is an exciting prospect but should only be undertaken when all the necessary pre-clinical data and regulatory approvals have been obtained and verified and the criteria for moving those cells to trials fully resolved and met. Acting prematurely has the potential not only to tarnish many years of scientific work, but can threaten to derail and damage this exciting field of regenerative medicine. Hopefully, in 2016, we are ready to take a more careful approach as we strive to repair the PD brain with stem cell-based therapies, avoiding many of the mistakes that have dogged this field over the last three decades.”

Original source : https://www.eurekalert.org/pub_releases/2016-03/ip-ast032916.php

 

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Falls, an early indicator of Parkinson’s disease

Las caídas, un indicador precoz de la enfermedad de Parkinson?

Studies show that falls could be a valuable indicator for the work of early prevention of Parkinson.

We know that early treatment of Parkinson’s disease improves the management of it.

Changes in lifestyle, dietary supplements, support from a medical and paramedical personnel can slow the progression of certain types of diseases. For patients with Parkinson’s disease, a large part of the dopamine nervous system is severely damaged by before the appearance of symptoms common misfortune. Therefore the diagnosis is very late in the evolution of the problem.

A case-control study in Sweden, published in the journal PLoS Medicine, has studied falls and hip fractures. The researchers found that patients of the parkinson disease had a current frequency of falls and hip fractures well above the average of the population and often long before the definitive diagnosis of the disease.

The smaller motor problems that lead falls could , according to the researchers, be an excellent way for early diagnosis of Parkinson’s disease. In fact, this type of accident significantly involved the group that was studied up to 26 years before the Declaration and the official diagnosis of the disease.

In fact, parkinson’s disease, with its characteristic symptoms of stiffness, tremor, loss of balance and others appear only once 50-80% of dopaminergic nerves are damaged.

Before developing reliable biomarkers for early diagnosis of this disease, falls could be a valuable tool for the early prevention work.

In combination with the advances in the development of solutions that could at least slow the progression of the disease, this early detection of predisposition may help to better understand this disease often too late discovered.

Original Source:

Risk of injurious Fall and Hip Fracture up to 26 and before the diagnosis of ParkinsonDisease: Nested Case-Control Studies in Nationwide Cohort Helena Nyström, Anna Nordström, PeterNordström.

  • PublishedFebruary 2, 2016
  • DOI: 10.1371 / journal.pmed.1001954
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Medical records documentation of constipation preceding Parkinson disease: A case-control study

OBJECTIVE:

Parkinson disease (PD) may affect the autonomic nervous system and may cause constipation; however, few studies have explored constipation preceding the motor onset of PD. We investigated constipation preceding PD using a case-control study design in a population-based sample.

METHODS:

Using the medical records-linkage system of the Rochester Epidemiology Project, we identified 196 subjects who developed PD in Olmsted County, MN, from 1976 through 1995. Each incident case was matched by age (+/-1 year) and sex to a general population control. We reviewed the complete medical records of cases and controls in the medical records-linkage system to ascertain the occurrence of constipation preceding the onset of PD (or index year).

RESULTS:

Constipation preceding PD or the index year was more common in cases than in controls (odds ratio [OR] 2.48; 95% confidence interval [CI] 1.49 to 4.11; p = 0.0005). This association remained significant after adjusting for smoking and coffee consumption (ever vs never), and after excluding constipation possibly induced by drugs. In addition, the association remained significant in analyses restricted to constipation documented 20 or more years before the onset of motor symptoms of PD. Although the association was stronger in women than in men and in patients with PD with rest tremor compared with patients with PD without rest tremor, these differences were not significant.

CONCLUSIONS:

Our findings suggest that constipation occurring as early as 20 or more years before the onset of motor symptoms is associated with an increased risk of Parkinson disease.

Author information: Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA