Mom's Story

A discussion about Mom's Story and MS…

Archive for the tag “Myelin”

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.

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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.

German Study Suggests Leukemia and Colorectal Cancer Rates Increased with Mitoxantrone Use for MS

Summary

  • A study of 676 people with MS treated with the MS therapy mitoxantrone in Germany reveals that the rates of acute myeloid leukemia (a type of cancer) and colorectal cancer were significantly increased above what would be expected in the general population there. Rates of other cancers were not increased.
  • The authors note that if the findings are confirmed, recommending colonoscopy after treatment may be advisable, since if found early enough, colorectal cancer is curable.
  • The team (led by Dr. Mathias Buttmann, University of Würzburg, Germany) has published results in Neurology (published early online, May 11, 2016).

Background: Mitoxantrone is a powerful immune-suppressing therapy. Prior to its approval for use in MS, it was used only to treat certain forms of cancer. It acts in MS by suppressing the activity of immune T cells, B cells, and macrophages that are thought to lead the attack on nerve-insulating myelin. The U.S. Food and Drug Administration approved mitoxantrone for reducing neurologic disability and/or the frequency of relapses in people with secondary progressive MS or worsening relapsing-remitting MS. The total lifetime dose is limited to avoid possible heart damage. Acute myeloid leukemia has been previously reported in people treated with mitoxantrone for MS or cancer.

The Study: Investigators identified 677 people with MS seen at the University of Würzburg MS center between January 1994 and December 2007 who had received mitoxantrone. They were able to follow up with 676 of these patients.

The results show that 37 people developed cancer after taking mitoxantrone, including nine cases of breast cancer, seven cases of colorectal cancer, and four cases of acute myeloid leukemia. The rate of acute myeloid leukemia was 10 times that seen in the general population in Germany. The rate of colorectal cancer was three times that seen in the general population in Germany. The rate of breast and other cancers was not increased over that seen in the general population in Germany. Older age at treatment was associated with increased risk of cancer, but not prior use of other immunosuppressive treatments, or duration of treatment with mitoxantrone.

The team (led by Dr. Mathias Buttmann, University of Würzburg, Germany) has published results in Neurology (published early online, May 11, 2016).

Comment: The authors state that if the findings are confirmed, “posttreatment colonoscopy might improve the risk-benefit ratio of this highly active immunosuppressive drug,” since if found early enough, colorectal cancer is curable. They also note that mitoxantrone is currently the only MS therapy approved for treating secondary progressive MS, and that the overall rate of cancers may still justify the use of mitoxantrone in people who are severely affected with MS and where there are no better treatment options available.

Read more about mitoxantrone
Read more about treating secondary progressive MS
Read more about making treatment decisions in MS

 

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 suggests possible inside-out origin for MS

A new study suggests an inside-out theory of multiple sclerosis in which the disease may be triggered by the death of brain cells that make the insulation around nerve fibers, according to a new study from Northwestern Medicine and the University of Chicago researchers. Creating a mouse-model of progressive MS, scientists also used a specially developed nanoparticle that prevented MS even after the death of those brain cells.
The new study shows the possibility that MS can begin from the inside out, in which damage to oligodendrocytes in the central nervous system can trigger an immune response directly. Oligodendrocytes can possibly be destroyed by developmental abnormalities, viruses, bacterial toxins or environmental pollutants. Oligodendrocytes are responsible for the maintenance of myelin. If they die, the myelin sheath falls apart. The death of these cells can activate the autoimmune response against myelin, which is the main feature of MS. The inside-out hypothesis suggests that when myelin falls apart, the immune system interprets the products of its degradation as foreign bodies or antigens, erroneously viewing them as invaders and beginning a full-scale attack on myelin, initiating MS.
“Protecting oligodendrocytes in susceptible individuals might help delay or prevent MS from initiating. It’s likely that therapeutic strategies that intervene early in the disease process will have greater impact,” said Brian Popko, the Jack Miller Professor of Neurological Disorders at the University of Chicago and one of the lead investigators in the study.
The scientists also developed the first mouse model of the progressive form of the autoimmune disease, which will enable the testing of new drugs against progressive MS. In the study, nanoparticles creating tolerance to the myelin antigen were administered and prevented progressive MS from developing. The nanoparticles are being developed for clinical trials that could lead to new treatments – without the side effects of current therapies – in adults.
The study was published in Nature Neuroscience.

Experimental drug that may repair nerve damage in MS moves forward

A new study suggests that an investigational drug for multiple sclerosis (MS) may repair myelin according to a study that will be presented at the American Academy of Neurology’s 67th Annual Meeting in Washington, DC, April 18 to 25, 2015.
“This study, for the first time, provides biological evidence of repair of damaged myelin in the human brain, and advances the field of neuro-reparative therapies,” said study lead author Diego Cadavid, MD, with Biogen in Cambridge, Mass., and a fellow with the American Academy of Neurology.
The Phase 2 study involved 82 people who had their first incident of acute optic neuritis, a disease that typically affects one eye and is characterized by inflammation, damage to the nerve fibers and loss of myelin within the optic nerve. It is estimated that about half of people with optic neuritis will later develop multiple sclerosis.
All participants were treated with high dose steroids and then randomly selected with equal probability to receive either the experimental antibody, called anti-LINGO-1, or a placebo once every four weeks, for a total of six doses. Participants were then assessed every four weeks for six months and a final visit at eight months. The drug’s effectiveness in repairing myelin was evaluated by comparing the recovery of the optic nerve latency in the damaged eye at six and eight months to the normal unaffected eye at the start of the study.
The main finding of the study focused on the latency of the visual evoked potential (VEP), a test that measures the visual system’s ability to conduct electrical signals between the retina and the brain. The results showed that people treated with the experimental drug and who did not miss more than one dose (per protocol population) had significantly improved conduction as measured by latency recovery compared to people who received the placebo. At six months, those who received the drug improved on average by 7.55 milliseconds, or 34 percent, compared to placebo. The effect continued to eight months with an average improvement of 9.13 milliseconds or 41 percent over placebo.
In addition, the percentage of subjects whose VEP latency in the affected eye recovered to normal or nearly normal (within 10 percent of the normal eye) more than doubled, from 26 percent on placebo to 53 percent on the drug.
A substudy using an exploratory method of measuring latency called multifocal VEP revealed similar treatment effects.
“More studies are needed to evaluate whether these changes lead to clinical improvement,” said Cadavid.
A second study of anti-LINGO-1 in people with multiple sclerosis is ongoing.
See more at: http://www.neuroscientistnews.com/clinical-updates/experimental-drug-may-repair-nerve-damage-ms-moves-forward#sthash.KsNzebw1.dpuf

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