Mom's Story

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Archive for the tag “brain”

Dawson’s Fingers ???

“Dawson’s fingers” is the name for the lesions around the ventricle-based brain veins of patients with multiple sclerosis. The condition is thought to be the result of inflammation or mechanical damage by blood pressure around long axis of medular veins.

Dawson’s fingers spread along, and from, large periventricular collecting veins, and are attributed to perivenular inflammation.

Lesions far away from these veins are known as Steiner’s splashes.

Sometimes experimental autoimmune encephalomyelitis has been triggered in humans by accident or medical mistake. The damage in these cases fulfils all the pathological diagnostic criteria of MS and can therefore be classified as MS in its own right. The lesions were classified as pattern II in the Lucchinetti system. This case of human EAE also showed Dawson fingers.

Study suggests antibody may have therapeutic effect on MS

Researchers have developed an antibody with potential therapeutic effects against multiple sclerosis. The discovery opens up a new strategy for controlling the disease.

For the cells of the immune system circulating in the bloodstream to reach the central nervous system, they must penetrate the blood-brain barrier and blood-spinal cord barrier. During previous work, the authors studied a factor involved in opening the blood-brain barrier, the NMDA receptor. They found that blocking the interaction of this receptor with tPA has beneficial effects linked with maintaining the integrity of the barrier.

Scientists at the Institut National de la Santé et de la Recherche Médicale, in France, developed a monoclonal antibody (Glunomab) directed against the specific site on the NMDA receptor to which tPA binds. In cellular models of the human blood-brain and blood-spinal cord barriers, the use of this antibody prevented opening of the barrier under inflammatory conditions, limiting the entry of lymphocytes. The team then tested the therapeutic effects of the antibody in an experimental mouse model of MS. After intravenous injection of Glunomab, the progression of partial or total paralysis of the limbs – as assessed by a clinical score – was blocked. In these treated mice, this effect was linked with reduced infiltration of lymphocytes into the nervous tissue, and reduced demyelination.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the authors argue that by preventing myelin destruction by the cells of the immune system, this strategy might represent a promising therapy for the control of MS.

The study was published in the journal Brain.

Study Shows Expansion of Stem Cell Clinics in the U.S. and the Need for Better Oversight

Researchers have published a paper describing the proliferation of stem cell clinics in the United States and ethical issues and regulatory concerns that come with marketing unproven treatments for many conditions. Their study shows that many different types of unproven stem cell treatments are being offered, and highlights concerns for the safety of people who undergo these treatments.

There is exciting progress being made through innovative research related to the potential of many types of stem cells for slowing MS disease activity and for repairing damage to the nervous system. At present, there are no approved stem cell therapies for MS. People need the best available information to understand this exciting area of research and make decisions related to this complex issue.

The paper’s findings support the need for stem cell therapy to be explored in the context of carefully conducted clinical trials that can determine what the optimal cells, delivery methods, safety and actual effectiveness of cell therapies might be for people with MS.

Positive Results from Study of Bone Marrow-Derived Stem Cells in People with Aggressive, Relapsing MS

Summary

  • Researchers in Canada have published results of a long-term trial of an individuals’ own (autologous) hematopoietic (blood cell-producing) stem cell transplantation. The study involved 24 people with aggressive relapsing-remitting MS whose disease was not controlled with available therapies.
  • Three years after the procedure, 70% remained free of disease activity, with no relapses, no new MRI-detected inflammatory brain lesions, and no signs of progression.
  • None of the surviving participants, who were followed for 4 to 13 years after the procedure, experienced clinical relapses or required MS disease-modifying therapies to control their disease, and 40% experienced reductions in disability.
  • One of the participants died and another required intensive hospital care for liver complications. All participants developed fevers, which were frequently associated with infections, and other toxicities.
  • Additional research is focusing on figuring out who might benefit from this procedure and how to reduce its risks.

“These results suggest that aggressive MS may be stopped with an effective but risky procedure, for a subset of people,” said Dr. Bruce Bebo, Executive Vice President, Research, at the National MS Society. “Additional research by investigators around the world is focusing on figuring out who might benefit from this procedure and how to reduce its risks, which can include death.”

Details
Background: An experimental procedure that has been explored for several years in MS is called “autologous hematopoietic (blood cell-producing) stem cell transplantation” – or HSCT. This procedure has been used in attempts to “reboot” the immune system, which launches attacks on the brain and spinal cord in people with MS.

In HSCT, the stem cells (derived from a person’s own bone marrow or blood) are stored, and the rest of the individual’s immune cells are depleted by chemotherapy. Then the stored stem cells are reintroduced by infusion into the vein. The new stem cells migrate to the bone marrow and over time produce new blood cells, including immune cells. The goal of this currently experimental procedure is to establish a new immune system that no longer recognizes myelin and other nervous system tissue as dangerous. In theory, this should stop the attacks that lead to tissue damage and disability.

There are a number of laboratories around the world testing variations of HSCT for the treatment of autoimmune diseases, including MS. Preliminary findings suggest this is a promising, but potentially risky strategy for the treatment of MS.

The Study: Drs. Harold Atkins, Mark Freedman and team at the Ottawa Hospital, University of Ottawa and other institutions in Canada conducted a Phase 2 trial of HSCT that involved 24 people with aggressive relapsing-remitting MS whose disease was not controlled with available therapies. No control group was used which would have enabled comparison against the results found in the treatment group. The procedure used by this group included complete destruction of bone marrow cells and an additional step that enriched the transplanted cells for stem cells.

Results – Safety: One of the participants died of transplantation-related complications that caused liver failure and another required intensive hospital care for liver complications. The treatment regimen was modified over the course of the study to reduce toxicity, but all participants still developed fevers, which were frequently associated with infections.

Results – Effectiveness: Three years after the procedure, 70% of the participants remained free of disease activity, meaning they had no relapses, no new MRI-detected inflammatory brain lesions, and no signs of progression. The remaining 30% experienced progression of disability. In addition, for the entire follow-up period ranging from 4 to 13 years after the procedure, of the 23 survivors:

  • None experienced clinical relapse, had new active inflammatory MRI brain lesions, or required MS disease-modifying therapies to control their disease.
  • The average rate of brain atrophy (shrinkage), a measure that has been linked to MS progression, returned to levels associated with normal aging.
  • 40 percent experienced some lasting reversal of disability such as vision loss, muscle weakness and balance problems.
  • Some were able to return to work or school.

The results were published online on June 9, 2016 in The Lancet.  Major funding for the study came from the MS Society of Canada and its affiliated Multiple Sclerosis Scientific Research Foundation.

Next Steps: Rigorous clinical trials of stem cell therapies are needed to determine their safety and effectiveness in people with MS. Trials of this and other stem cell therapy approaches are taking place in Canada, the United States, Europe and elsewhere. To help explore the potential of stem cell therapy, in November 2015, the International Conference on Cell-Based Therapy for Multiple Sclerosis was convened in Lisbon, Portugal under the auspices of the International Advisory Committee on Clinical Trials in MS (a group jointly sponsored by the National MS Society and the European Committee for Treatment and Research in Multiple Sclerosis). Seventy leading researchers and clinicians conferred on clinical trials needed to provide answers about which types of cells, which route of delivery, and which types and stages of disease, would be the most promising approach for treating MS. Read more about this meeting

Read more about stem cells and MS

Canadian Researchers Uncover Rare Gene that Increases Risk of Progressive MS

Researchers at the University of British Columbia have uncovered a rare gene mutation that appears to dramatically increase the risk, in some individuals, of developing a severe form of progressive multiple sclerosis. While the cause of MS is not known, scientists believe several different factors, including susceptibility genes, may interact to trigger the disease. The gene was discovered in two unrelated families that had multiple members with MS. The researchers also determined that the gene (NR1H3) contains instructions for a protein called LXRA, which is thought to be a control switch for genes involved in many functions, including some that help control inflammation and integrity of nerve-insulating myelin in the brain and spinal cord. This type of discovery can provide crucial clues to biological pathways that underlie MS, and may lead to new approaches for stopping MS and restoring function. The study, by Drs. Carles Vilariño-Güell, Weihong Song, A. Dessa Sadovnick and others, was funded in part by the MS Society of Canada and appeared in the journal Neuron on June 1, 2016.

Multiple Sclerosis in Russia

From the Russian Multiple Sclerosis Society (http://www.armss.ru/)

Multiple Sclerosis (MS) is a severe chronic disease of the brain and spinal cord, which affects relatively young people and oftentimes results in disabilities. Over recent years, MS has tended to rapidly grow in frequency with onset among younger patients. This was caused by not only better diagnostic facilities for MS but also improvement of the quality of epidemiological research, yet the actual growth of the disease is also a reason. Currently, there are over 150,000 patients in Russia, of whom no less than 75% are already disabled. While including the families of patients and disabled people, MS as a problem involves from 750,000 to 1 million Russian citizens.  At present, there are about 3 million people with MS in the world. The MS frequency in Russia is from 30 to 100 per 100,000 of general population.

In Russia,

70%    families break up after one of the spouses is diagnosed

29%    patients have not left their homes for over a year

78%   patients are females under 50

75%    patients have disabilities

35%    are young people under 28

6%     are children aged 10-15

Medical and social support for PwMS is a challenging and complex task, which cannot be resolved otherwise but in close cooperation between civil institutions, as well as expert and public ones. Since the course of the disease is unpredictable with the end deemed practically inevitable, while diagnostic facilities were untimely and pathogenic therapies were highly expensive and disabilities growing, some time ago patients with MS would not often get an adequate medical and social treatment as they were regarded as having no prospects. With introducing a range of medicines in the 90s of the 20th century to modify the course of multiple sclerosis (or, disease modifying drugs – DMDs), then, new medical and rehabilitation techniques, patients got a hope for the pathological process development to slow down, to prolong physical activity and working ability and quality of life.

However, MS requires overall significant resources employed being financial, organizational, scientific-methodic, social. In the 90s of the last century, the problem remained little-known and was considered by professionals as a specific scientific-medical one. For a long time, authorities and professional and general communities underestimated its high social significance and the necessity to concentrate on considerable efforts to fight it.

Nurse assistance services have been set up in 55 regions that carry out target medical maintenance of patients receiving highly expensive medicinal therapy. Nurses render consulting medical and social assistance to people with MS.

The crowning achievement of the ARMSS is that it has managed to translate, in the general public mind, MS as a problem from the ‘scientific and medical’ category into the ‘social and economic’ one, as well as to improve the quality of rendering medical assistance to Russians suffering from MS.  The most outstanding result of this understanding became the guaranteed provision of highly expensive medicines (DMDs) for patients with MS at the expense of federal and regional budgets, which had been unthinkable of in the early 2000s.

The improvement of quality of life of people with MS is a result of combined activities of structures of civil society and authorities.

(after:  Patient voluntary organizations’ role in improving the quality of rendering social and medical assistance to communities. by Yan V. Vlasov – MD, Mikhail Al. Kurapov, Mikhail V. Churakov – PhD)

Antihistamine Shows Evidence of Stimulating Myelin Repair in Small Phase II MS Study – More studies needed before the full benefits and risks of this approach can be verified

Summary

  • In a small, phase II clinical trial, the oral antihistamine clemastine modestly improved the transmission of electrical signals in the optic nerve in participants with MS who had optic nerve damage.
  • The improved transmission indicates that nerve-insulating myelin was repaired along the nerve pathways.
  • Clemastine is an over-the-counter allergy medication. Doses in this trial exceeded the maximum recommended for over-the-counter use. Clemastine affects a range of targets in the body, and involves the risk for side effects, particularly at increased dosages.
  • This team is planning an additional trial to further determine the safety and effectiveness of clemastine, as well as studies to identify compounds that may enhance myelin repair and cause fewer side effects.
  • Clemastine was identified as having possible myelin-repairing properties through innovative preclinical research conducted by National MS Society-funded Jonah Chan, PhD, who went on to become first recipient of the Barancik Prize for Innovation in MS Research for this pioneering work.
  • Preliminary results will be presented by the clinical trial’s lead investigator Ari Green, MD (University of California, San Francisco), at the annual meeting of the American Academy of Neurology being held in Vancouver, Canada, April 15 to 21.

Background: In MS, the immune system attacks and destroys myelin, the fatty substance that surrounds and protects the nerve fibers, and the nerve fibers can also be damaged. Current therapies are largely aimed at dampening the immune attacks. However, a therapy that repairs damage to myelin and nerve fibers is also necessary.
A team at the University of California, San Francisco led by National MS Society-funded Harry Weaver Neuroscience Scholar Jonah Chan, PhD, invented a new micropillar technology to rapidly identify compounds that stimulate the regrowth of myelin. The team initiated a screen using this technology, testing a library of 1000 drugs already approved by the FDA for other conditions for their ability to promote the development of myelin-making cells and wrapping of myelin around the micropillars. Clemastine, an oral antihistamine used to treat allergy symptoms, was identified through this process. Dr. Chan was the first recipient of the Barancik Prize for Innovation in MS Research for this pioneering work.

The Clinical Trial: Ari Green, MD, led the team conducting the clinical trial. They administered oral clemastine or inactive placebo twice daily to 50 people with MS and optic nerve damage for 150 days. For the first three months of the study, people were given either clemastine or a placebo, and for the second two months, those initially given clemastine received the placebo and vice-versa. Tests were performed before and after treatment that measured visual evoked potentials. Visual evoked potentials measure transmission of electric signals along optic nerve pathways in response to stimulation. Delays in this transmission occur when the myelin is damaged and if these delays are reduced, it is an indication that myelin repair is occurring along the nerve pathways. (Participants had significant delays in transmission in at least one eye.)

Delays in visual evoked potential were reduced by 1.9 milliseconds per eye, a statistically significant result. The results hinted at a reduction in vision impairment as well, but it did not reach statistical significance. Fatigue increased mildly in participants taking clemastine.

Clemastine is an over-the-counter allergy medication. Doses in this trial exceeded the maximum recommended for over-the-counter use. Also, clemastine affects a range of targets in the body, and involves the risk for side effects, particularly at increased dosages.

Dr. Green cautions that more research with larger numbers of people is needed before doctors can recommend clemastine as a treatment for people with MS. This team is planning an additional trial to further determine the safety and effectiveness of clemastine, as well as studies to identify compounds that may enhance myelin repair and cause fewer side effects.

Drs. Green and Chan both received Society funding to launch their early careers as independent researchers focused on MS, including Harry Weaver Neuroscience Scholar Awards.

Comment: “This preliminary report is exciting, and we look forward to seeing the full results of this clinical trial of clemastine presented and then published,” says Bruce Bebo, PhD, Executive Vice President, Research at the National MS Society. “Finding a way to repair nervous system damage to restore function to people with MS is a very high research priority.”

The 2016 Annual Meeting of the American Academy of Neurology will take place in Vancouver, BC, Canada, April 15-21. The National MS Society will be providing reports summarizing studies. Anyone can get a preview of the technical summaries, or abstracts, of presentations to be given at the meeting at this link, free of charge. 

Study finds greater role for environment in MS

Environmental factors may be playing a much greater role in the onset of multiple sclerosis than previously realized, according to early research led by Queen Mary University of London and Barts Health NHS Trust. The theory is based on new findings showing that Black people and South Asians in east London have a higher prevalence of MS compared to those groups in their ancestral countries, indicating a strong environmental influence on the disease that could be driving higher MS rates in London.

The researchers, led by Dr. Klaus Schmierer, used electronic records from general practices in four east London boroughs (Tower Hamlets, Newham, Hackney and City of London) which were reviewed for the number of MS-diagnosed patients, grouped by ethnicity. What they found was that MS appeared to be several times more prevalent among African people and South Asians living in London compared to those groups living in their ancestral territory. While prevalence differences could be explained by fewer MS diagnoses occurring in less resourced countries, the authors said it is unlikely to explain the gulf in prevalence between these territories. They said that an alternative, or additional, explanation would be increased exposure in the UK to environmental agents or behaviors that facilitate the development of MS.

Lead author Schmierer said, “MS is a disease where genetic ancestry and environmental factors play a role, however to what degree these two aspects are driving the risk of developing MS remains unknown. We found that people of Asian and African extraction in London are far more likely to have MS than people of the same ethnicity living in their ancestral countries. Our early results suggest that environmental factors play a pivotal role in the risk of developing MS, while the individual genetic backdrop may be of lesser importance.”

The study was published in Multiple Sclerosis Journal.

Brain-training Video Games May Help MS Patients

A new study suggests that playing a certain kind of video game strengthens neural connections in the brains of people with multiple sclerosis, improving cognitive abilities. Researchers hope to study whether the plasticity induced by video games in MS patients is linked to improvements in other aspects of their daily lives. They also plan to look at how the video game can be integrated into a rehabilitation program.
Researchers, led by Dr. Laura De Giglio, from the Department of Neurology and Psychiatry at Sapienza University in Rome, studied the effects of a video game-based cognitive rehabilitation program on the thalamus in patients with MS. They used a collection of Nintendo video games, called Dr. Kawashima’s Brain Training, which train the brain using puzzles, word memory and other mental challenges.
Twenty-four MS patients with cognitive impairment were randomly assigned to either take part in an eight-week, home-based rehabilitation program — consisting of 30-minute gaming sessions, five days per week — or be put on a wait list, serving as the control group. Patients were evaluated by cognitive tests and by 3-Tesla resting state functional MRI at baseline and after the eight-week period. At follow-up, the 12 patients in the video-game group had significant increases in thalamic functional connectivity in brain areas corresponding to the posterior component of the default mode network, which is one of the most important brain networks involved in cognition.
The modifications in functional connectivity shown in the video game group after training corresponded to significant improvements in test scores assessing sustained attention and executive function. The results suggest that video-game-based brain training is an effective option to improve cognitive abilities of patients with MS.

Researchers Funded by National MS Society Pinpoint Direct Damage to Nerve Connections in Mice, Independent of Myelin Damage

Summary
• Researchers have found evidence that microscopic connectors in the brain called “synapses” are directly damaged during the course of MS-like disease in mice, in an area of the brain linked to cognitive function.
• The damage appeared to be unrelated to myelin damage, and was linked to a specific molecule called platelet-activating factor receptor.
• Further research will determine whether treatment that protects synapses in the hippocampus may preserve cognitive function in people with MS. The team is pursuing therapeutic candidates based on these findings.
• This research was funded in part by a National MS Society-American Brain Foundation (American Academy of Neurology) Clinician Scientist Development Award to Dr. Matthew Bellizzi.
• The team (Drs. Bellizzi, Harris Gelbard, and colleagues, from the University of Rochester Medical Center, in New York) has published results in The Journal of Neuroscience. (2016 Jan 27;36(4):1336-46.)
Background: MS involves immune attacks in the brain and spinal cord. During the course of MS, damage occurs to the myelin that surrounds and protects nerve fibers, and nerve cells and their axons are also damaged. Damage to nerve cells in MS has been linked to cognitive impairment, progressive disability and other symptoms.

The causes of nerve damage are not yet well understood, which has limited progress in developing therapies that prevent damage and preserve nerve function (neuroprotection) to slow or stop progressive disability. Some research has shown that microscopic connectors in the brain called “synapses” may be lost in some parts of the brain during the course of MS, but details have been lacking. Synapses are the point of communication between individual nerve cells, and they are critically important for all functions of the nervous system including memory. A team at the University of Rochester has been attempting to determine the extent of damage to nerve cell fibers and synapses in brain, to find ways to protect nerves from damage.

The Study: The team, led by Matthew Bellizzi, MD, PhD, and Harris Gelbard, MD, PhD (University of Rochester), studied mice with the MS-like disease EAE. They measured the density of synapses in an area of the brain called the hippocampus. The hippocampus is involved in memory function. Although myelin was preserved, synaptic density was reduced by 28%, compared with mice that did not have EAE.

In another study, the team grew nerve cells from the hippocampus in laboratory dishes, and then added brain cells called microglia. This made the synapses more vulnerable to damage, and this damage seemed to be dependent on signals from a molecule called platelet-activating factor receptor (PAFR). To test this, the team administered an experimental molecule – BN52021 – that inhibits PAFR. Administering this molecule before EAE developed did not prevent the disease, but preserved synapses.

This research was funded in part by a National MS Society-American Brain Foundation (American Academy of Neurology) Clinician Scientist Development Award to Dr. Matthew Bellizzi. The team published results in The Journal of Neuroscience. (2016 Jan 27;36(4):1336-46.)

Next Steps: Further research will determine whether treatment that preserves synapses in the hippocampus can improve cognitive function in people with MS. According to a press release from the University of Rochester, the researchers are now focused on exploring potential therapeutic candidates based on these findings.

Read more about research to repair damaged tissue in MS
Read more about efforts to understand how MS affects cognitive function
Watch the educational video, Mood & Cognition in MS: [What you can do].

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