We are led to question whether the recommended social distancing measures to prevent SARS-CoV-2 transmission could increase the number of other serious instabilities. The breaking of the contagion pathways reduces the sharing of microorganisms between people, thus favoring dysbiosis, which, in turn, may increase the poor prognosis of the disease. #covid #microbiome #dysbiosis Célia P. F. Domingues, João S. Rebelo, Francisco Dionisio, Ana Botelho, Teresa Nogueira. The Social Distancing Imposed To Contain COVID-19 Can Affect Our Microbiome: a Double-Edged Sword in Human Health. mSphere, 2020; 5 (5) DOI: 10.1128/mSphere.00716-20 https://msphere.asm.org/content/5/5/e00716-20
By accident researchers discovered that a guardian molecule cytokine IL-33 that was produced due to testosterone eliminated MS symptoms in mice.
Male-specific IL-33 expression regulates sex-dimorphic EAE susceptibility. Proceedings of the National Academy of Sciences, 2018; 201710401 DOI: 10.1073/pnas.1710401115
Vaccines and the Risk of Multiple Sclerosis and Other Central Nervous System Demyelinating Diseases
JAMA Neurol. Published online October 20, 2014. doi:10.1001/jamaneurol.2014.2633
Importance Because vaccinations are common, even a small increased risk of multiple sclerosis (MS) or other acquired central nervous system demyelinating syndromes (CNS ADS) could have a significant effect on public health.
Objective To determine whether vaccines, particularly those for hepatitis B (HepB) and human papillomavirus (HPV), increase the risk of MS or other CNS ADS.
Design, Setting, and Participants A nested case-control study was conducted using data obtained from the complete electronic health records of Kaiser Permanente Southern California (KPSC) members. Cases were identified through the KPSC CNS ADS cohort between 2008 and 2011, which included extensive review of medical records by an MS specialist. Five controls per case were matched on age, sex, and zip code.
Exposures Vaccination of any type (particularly HepB and HPV) identified through the electronic vaccination records system.
Main Outcomes and Measures All forms of CNS ADS were analyzed using conditional logistic regression adjusted for race/ethnicity, health care utilization, comorbid diseases, and infectious illnesses before symptom onset.
Results We identified 780 incident cases of CNS ADS and 3885 controls; 92 cases and 459 controls were females aged 9 to 26 years, which is the indicated age range for HPV vaccination. There were no associations between HepB vaccination (odds ratio [OR], 1.12; 95% CI, 0.72-1.73), HPV vaccination (OR, 1.05; 95% CI, 0.62-1.78), or any vaccination (OR, 1.03; 95% CI, 0.86-1.22) and the risk of CNS ADS up to 3 years later. Vaccination of any type was associated with an increased risk of CNS ADS onset within the first 30 days after vaccination only in younger (<50 years) individuals (OR, 2.32; 95% CI, 1.18-4.57).
Conclusions and Relevance We found no longer-term association of vaccines with MS or any other CNS ADS, which argues against a causal association. The short-term increase in risk suggests that vaccines may accelerate the transition from subclinical to overt autoimmunity in patients with existing disease. Our findings support clinical anecdotes of CNS ADS symptom onset shortly after vaccination but do not suggest a need for a change in vaccine policy.
Melatonin consumption shown to help increase metabolism /Burn fat
* Journal of Pineal Research : 26 SEP 2013
Multiple Sclerosis reversed in 100% of animals using Calcitriol & ongoing Vitamin D Sup
* Journal of Neuroimmunology : Online August addition
ScienceDaily (Nov. 18, 2012) — In a breakthrough for nanotechnology and multiple sclerosis, a biodegradable nanoparticle turns out to be the perfect vehicle to stealthily deliver an antigen that tricks the immune system into stopping its attack on myelin and halt a model of relapsing remitting multiple sclerosis (MS) in mice, according to new Northwestern Medicine research.
The new nanotechnology also can be applied to a variety of immune-mediated diseases including Type 1 diabetes, food allergies and airway allergies such as asthma.
In MS, the immune system attacks the myelin membrane that insulates nerves cells in the brain, spinal cord and optic nerve. When the insulation is destroyed, electrical signals can’t be effectively conducted, resulting in symptoms that range from mild limb numbness to paralysis or blindness. About 80 percent of MS patients are diagnosed with the relapsing remitting form of the disease.
The Northwestern nanotechnology does not suppress the entire immune system as do current therapies for MS, which make patients more susceptible to everyday infections and higher rates of cancer. Rather, when the nanoparticles are attached to myelin antigens and injected into the mice, the immune system is reset to normal. The immune system stops recognizing myelin as an alien invader and halts its attack on it.
“This is a highly significant breakthrough in translational immunotherapy,” said Stephen Miller, a corresponding author of the study and the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. “The beauty of this new technology is it can be used in many immune-related diseases. We simply change the antigen that’s delivered.”
“The holy grail is to develop a therapy that is specific to the pathological immune response, in this case the body attacking myelin,” Miller added. “Our approach resets the immune system so it no longer attacks myelin but leaves the function of the normal immune system intact.”
The nanoparticle, made from an easily produced and already FDA-approved substance, was developed by Lonnie Shea, professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering and Applied Science.
“This is a major breakthrough in nanotechnology, showing you can use it to regulate the immune system,” said Shea, also a corresponding author. The paper will be published Nov. 18 in the journal Nature Biotechnology.
Miller and Shea are also members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. In addition, Shea is a member of the Institute for BioNanotechnology in Medicine and the Chemistry of Life Processes Institute.
Clinical Trial for Ms Tests Same Approach — With Key Difference
The study’s method is the same approach now being tested in multiple sclerosis patients in a phase I/II clinical trial — with one key difference. The trial uses a patient’s own white blood cells — a costly and labor intensive procedure — to deliver the antigen. The purpose of the new study was to see if nanoparticles could be as effective as the white blood cells as delivery vehicles. They were.
The Big Nanoparticle Advantage for Immunotherapy
Nanoparticles have many advantages; they can be readily produced in a laboratory and standardized for manufacturing. They would make the potential therapy cheaper and more accessible to a general population. In addition, these nanoparticles are made of a polymer called Poly(lactide-co-glycolide) (PLG), which consists of lactic acid and glycolic acid, both natural metabolites in the human body. PLG is most commonly used for biodegradable sutures.
The fact that PLG is already FDA approved for other applications should facilitate translating the research to patients, Shea noted. Miller and Shea tested nanoparticles of various sizes and discovered that 500 nanometers was most effective at modulating the immune response.
“We administered these particles to animals who have a disease very similar to relapsing remitting multiple sclerosis and stopped it in its tracks,” Miller said. “We prevented any future relapses for up to 100 days, which is the equivalent of several years in the life of an MS patient.”
Shea and Miller also are currently testing the nanoparticles to treat Type one diabetes and airway diseases such as asthma.
Nanoparticles Fool Immune System
In the study, researchers attached myelin antigens to the nanoparticles and injected them intravenously into the mice. The particles entered the spleen, which filters the blood and helps the body dispose of aging and dying blood cells. There, the particles were engulfed by macrophages, a type of immune cell, which then displayed the antigens on their cell surface. The immune system viewed the nanoparticles as ordinary dying blood cells and nothing to be concerned about. This created immune tolerance to the antigen by directly inhibiting the activity of myelin responsive T cells and by increasing the numbers of regulatory T cells which further calmed the autoimmune response.
“The key here is that this antigen/particle-based approach to induction of tolerance is selective and targeted. Unlike generalized immunosuppression, which is the current therapy used for autoimmune diseases, this new process does not shut down the whole immune system,” said Christine Kelley, National Institute of Biomedical Imaging and Bioengineering director of the division of Discovery Science and Technology at the National Institutes of Health, which supported the research. “This collaborative effort between expertise in immunology and bioengineering is a terrific example of the tremendous advances that can be made with scientifically convergent approaches to biomedical problems.”
“We are proud to share our expertise in therapeutics development with Dr. Stephen Miller’s stellar team of academic scientists,” said Scott Johnson, CEO, president and founder of the Myelin Repair Foundation. “The idea to couple antigens to nanoparticles was conceived in discussions between Dr. Miller’s laboratory, the Myelin Repair Foundation’s drug discovery advisory board and Dr. Michael Pleiss, a member of the Myelin Repair Foundation’s internal research team, and we combined our efforts to focus on patient-oriented, clinically relevant research with broad implications for all autoimmune diseases. Our unique research model is designed to foster and extract the innovation from the academic science that we fund and transition these technologies to commercialization. The overarching goal is to ensure this important therapeutic pathway has its best chance to reach patients, with MS and all autoimmune diseases.”
2009 study posted for filing
Neurologists Investigate Possible New Underlying Cause of MS (43 FOLD Increase)
UB neurologist Robert Zivadinov is principal investigator on a new study that could change understanding of MS.
BUFFALO, NY – Neurologists at the University at Buffalo are beginning a research study that could overturn the prevailing wisdom on the cause of multiple sclerosis (MS).
The researchers will test the possibility that the symptoms of MS result from narrowing of the primary veins outside the skull, a condition called “chronic cerebrospinal venous insufficiency,” or CCSVI.
CCSVI is a complex vascular condition discovered and described by Paolo Zamboni, M.D., from Italy’s University of Ferrara. In the original Italian patients, CCSVI was found to be strongly associated with MS, increasing the risk of developing MS by 43 fold.
This narrowing restricts the normal outflow of blood from the brain, causing alterations in the blood flow patterns within the brain that eventually causes injury to brain tissue and degeneration of neurons.
“If we can prove our hypothesis, that cerebrospinal venous insufficiency is the underlying cause of MS,” said Robert Zivadinov, M.D., Ph.D., UB associate professor of neurology, director of the Buffalo Neuroimaging Analysis Center (BNAC) and principal investigator on the study, “it is going to change the face of how we understand MS.”
Michael Cain, M.D., professor and dean of the UB School of Medicine and Biomedical Sciences, said a positive outcome from this trial would have enormous implications for the treatment of MS. “Being able to identify those at risk of developing MS before symptoms take their toll could change the lives of millions of persons who now face inevitable lifestyle restrictions.”
Margaret Paroski, M.D., executive vice president and chief medical officer of Kaleida Health, parent of Buffalo General Hospital where the BNAC is located, commented: “Will Rogers once said, ‘It isn’t what we don’t know that gives us trouble, it’s what we do know that ain’t so’. Challenging basic assumptions about diseases has lead to some very important discoveries.
“When I was in medical school, we thought peptic ulcer disease was due to stress. We now know that 80 percent of cases are due to a bacterial infection. Dr. Zivadinov’s work may lead to a whole different way of thinking about multiple sclerosis.”
The preliminary findings were based on a pilot study at the BNAC headed by Zivadinov, and at the Universities of Ferrara and Bologna, Italy, directed by Zamboni and Fabrizio Salvi, M.D, respectively. The study showed that several abnormalities affecting the predominant pathways that return venous blood from the brain to the heart occurred more frequently in MS patients than in controls.
This research, supported by the Hilarescere Foundation of Italy and the BNAC, was conducted to replicate the findings of the Italian investigators.
“Results of this preliminary study, which involved 16 relapsing-remitting MS patients and eight age-and-sex-matched healthy controls, showed that all the MS patients, but none of the controls, had chronic insufficient blood flow out of the brain,” said Zivadinov.
Bianca Weinstock-Guttman, M.D., UB associate professor of neurology and a co-principal investigator on the pilot study, added: “The images from this study were acquired using a method called Doppler ultrasound. The method identified anomalies in the venous blood flow associated with strictures, malformed valves and peculiar webs within the large veins of the neck and brain”
Weinstock-Guttman directs the Baird Multiple Sclerosis Center at the Jacobs Neurological Institute (JNI), UB’s Department of Neurology. The JNI and BNAC are located in Buffalo General Hospital of Kaleida Health.
Advanced magnetic resonance imaging scanning (MRI) of the MS study patients conducted at the BNAC also identified distinct areas of iron deposits in the brain, and showed that those deposits may be associated with the location of MS lesions and sites of impaired drainage. The scans also revealed increased brain atrophy and changes in the flow of cerebrospinal fluid in the MS patients.
These results, which form the basis of the current larger investigation, were presented at the 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis held in September in Dusseldorf, Germany
The new study will involve 1,600 adults and 100 children. The cohort will be comprised of 1,100 patients who were diagnosed with possible or definite MS, 300 age-and-sex matched normal controls, and 300 patients with other autoimmune and neurodegenerative diseases. Enrollment in the study has begun and will continue for two years. MS patients from across the U.S. are eligible to participate in the study.
“The prevailing wisdom that central nervous system damage in MS is predominantly the result of abnormal immune responses against the patient’s nervous tissue has been challenged by research findings, which have demonstrated a significant neurodegenerative component in MS and the progressive loss of neurons” said Zivadinov.
However, these inflammatory and neurodegenerative processes occur concurrently in MS and vary considerably among patients, making it difficult to identify the cause, or causes of the disease. Consequently, the origin and development of MS remains poorly understood, and its cause remains elusive.”
To determine if these preliminary findings can be repeated, Zivadinov and Weinstock-Guttman organized the present study, which will evaluate both the velocity of blood flow through both the brain’s blood vessels and the extracranial veins, using Doppler ultrasound.
The technical name of the study is “combined transcranial and extracranial venous Doppler (CTEVD) evaluation in MS and related diseases”.
All study subjects will undergo a general clinical examination and a Doppler scan of the head and neck to acquire images of the direction of venous blood flow in different body postures. Participants also will provide blood samples, and complete an extensive environmental questionnaire to identify potential MS risk factors.
All MS patients will undergo MRI of the brain to measure iron deposits in lesions and surrounding areas of the brain using a method called susceptibility-weighted imaging. Iron findings on these images will be related to neuropsychological symptoms. The neuropsychological part of the study will be conducted by Ralph Benedict, Ph.D., professor of neurology and psychiatry at the JNI, UB’s Department of Neurology.
A sub-cohort of 250 consecutive patients and controls will undergo MRI of the veins of the neck to confirm diagnosis of CCSVI.
Murali Ramanathan, Ph.D., associate professor in the Department of Pharmaceutical Sciences, UB School of Pharmacy and Pharmaceutical Sciences, will analyze blood samples for proteins and soluble factors associated with central nervous system injury. He also will be looking for other factors of interest in MS research, such as vitamin D metabolites and cigarette smoking, which have been linked to increased risk for developing MS as well as MS disease progression.
The data will be unblinded at three predetermined time-points, with the initial unblinding scheduled for November 2009. For more details on the study, send an email to email@example.com.
Zivadinov said results of the study may lead to a larger multicenter North-American trial that will evaluate the occurrence of CCSVI in MS.
Public release date: 25-Sep-2008 Re-Posted for Filing
Majority of children vaccinated against hepatitis B not at increased risk of MS
ST. PAUL, Minn. – The majority of children vaccinated against hepatitis B are not at an increased risk of developing multiple sclerosis (MS), according to a study to be published in the October 8, 2008, online issue of Neurology®, the medical journal of the American Academy of Neurology.
The study based in France involved 349 children with MS and 2,941 children without the disease. The children were all under the age of 16. A total of 24.4 percent of the children with MS were vaccinated for hepatitis B in the three years before the study, compared to 27.3 percent for the children without MS.
Although the study found that hepatitis B vaccination does not generally increase the risk of multiple sclerosis, the children with MS were 1.74 times more likely to have received a certain type of hepatitis B vaccine, called Engerix B®. Those children with MS developed symptoms three or more years after the vaccine. The risk was only found for this specific type of hepatitis B vaccine and not found for all vaccines against hepatitis B.
This association cannot be taken as confirmation that the vaccine caused MS. Further studies are needed to determine whether this is a causal relationship.
The American Academy of Neurology, an association of more than 21,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as stroke, Alzheimer’s disease, epilepsy, Parkinson’s disease, and multiple sclerosis.
For more information about the American Academy of Neurology, visit www.aan.com.
- Maligned molecule found to have beneficial anti-inflammatory effect
PUBLISHED:05:43 EST, 3 August 2012 | UPDATED:06:11 EST, 3 August 2012
A molecule that causes Alzheimer’s disease could reverse paralysis caused by multiple sclerosis (MS), a study has found.
The much-maligned molecule, known as A-beta, has until now been known as the chief culprit behind Alzheimer’s.
But it is also found in multiple-sclerosis lesions, which occur when immune cells invade the brain and spinal cord and attack the insulating coatings of nerve cells.
The nerve signals then get mixed up leading to blindness, loss of muscle control and difficulties with speech, thought and attention
Scientists from Stanford University in the United States wanted to investigate the role the molecule played in MS.
They used a mouse model that mimics several features of the disease – including the autoimmune attack on myelinated sections of the brain. They then injected A-beta into the rodent’s belly.
The scientists had suspected the injection would exacerbate the MS, but the opposite happened.
This shows that when A-beta is injected outside the brain it moderates and can even reverse symptoms of MS and does not cause Alzheimer’s in the mouse.
The researchers believe the startling discovery will open new avenues in the fight against MS, a hugely debilitating condition which affects around 100,000 people in the UK.
Laboratory tests also showed that A-beta countered not only visible symptoms such as paralysis, but also the increase in certain inflammatory molecules that characterises multiple-sclerosis flare-ups.
Lawrence Steinman, an MS expert and lead author of the report, which is published Science Translational Medicine, said: ‘This is the first time A-beta has been shown to have anti-inflammatory properties.’
Lennart Mucke, director of the Gladstone Institute of Neurological Disease in San Francisco and a veteran Alzheimer’s researcher, noted that while A-beta is toxic in the brain, it can have a very different effect elsewhere in the body.
He said: ‘A-beta is made throughout our bodies all of the time. But even though it’s been studied for decades, its normal function remains to be identified.
‘Most intriguing, to me, is this peptide’s potential role in modulating immune activity outside the brain.
‘There probably is a multiple-sclerosis drug in all this somewhere down the line,’ he said.
Researchers with the UBC Hospital MS Clinic and Brain Research Centre at Vancouver Coastal Health and the University of British Columbia have published important data in the Journal of the American Medical Association (JAMA) about the impact of a common drug therapy on the progression of multiple sclerosis for people with the relapsing‑remitting form of the disease.
The study, led by Drs. Helen Tremlett, Afsaneh Shirani, Joel Oger and others, shows no strong evidence that a group of drugs, beta interferons (β-IFNs), prescribed to treat MS had a measurable impact on the long-term disability progression of the disease.
The team examined the linked health records of 2656 BC patients between 1985 – 2008 in a retrospective cohort study, which means data from already collected sources were linked together in an anonymized form and studied. Data sources included the BC Ministry of Health, PharmaNet and the BC Multiple Sclerosis (BCMS) database, facilitated by Population Data BC.
The study population included patients with MS who were treated with beta interferons (β-IFNs), the most widely used treatment for relapsing‑remitting MS, as well as untreated MS patients. The research team discovered that administration of β-IFN was not associated with a significant change in the progression of disability.
These findings will be of interest to MS patients with this form of the disease, but researchers are quick to point out that this is just one measure of these disease modifying drugs and there is still potentially significant benefit to patients.
“What this study provides is additional information to patients and clinicians about the longer term effect of this class of drugs,” says corresponding author, Dr. Helen Tremlett (PhD), who also holds the Canada Research Chair in Neuroepidemiology and Multiple Sclerosis at UBC. “We know that this class of drugs is very helpful in reducing relapses, which can be important to patients. We do not recommend that patients stop taking these medications, but these findings provide evidence, allowing more realistic expectations as to the anticipated benefits associated with drug treatment from the disability perspective.”
“It is still possible that some patients gain long-term benefit from β-IFNs. We are currently working toward identifying who those potential treatment responders might be,” says Dr Afsaneh Shirani, who is the first author of the paper and a post-doctoral research fellow in the UBC Faculty of Medicine and Brain Research Centre at UBC and VCH Research Institute. “Our study also encourages the investigation of novel treatments for MS,” she adds.
“In addition, this study suggests that linked data from health administrative databases have enormous potential for research applications, despite all the challenges of record linkage” says Dr Shirani.
Relapsing-remitting MS is characterized by relapses or “flare-ups” during which time new symptoms can appear or old ones can resurface or worsen. The relapses are followed by periods of remission during which time the person can fully or partially recover. Relapsing-remitting MS is the most common form of MS affecting around 85% of MS patients in Canada.
“In clinical trial situations, it has been quite evident for years that patients receiving β-IFN treatment have reduced frequency of relapses as well as reduced frequency of new lesions seen on MRI,” says Dr. Joel Oger, who is also a neurologist with the UBC Hospital MS Clinic. “This study following a large number of patients for a long time in “real life situation” does not show an association of the β-IFNs with long term disability and tends to confirm a more modern way of understanding MS: relapses may not be responsible for long term disability in all patients and another mechanism might be at work as well.”
The research team is preparing for future studies further examining this and other classes of disease modifying drugs. The hope is that the research will ultimately lead to an individualized approach to the treatment of MS.