Mom's Story

A discussion about Mom's Story and MS…

Archive for the tag “inflamation”

Australian Team Finds Possible Molecular Pathway for MS Progression

Researchers from Australia report that the amount of molecules in a sequence of chemical reactions called the kynurenine pathway differs between people with MS and healthy controls, and between people with relapsing-remitting and progressive forms of MS. The kynurenine pathway is activated by chronic inflammation, and its activation may be involved in nerve damage and MS progression.  The kynurenine pathway has also been implicated in other neurological and psychiatric disorders. The MS-specific findings, and the potential use of the kynurenine pathway in a diagnostic test, will need to be explored in additional studies.

This work was funded by the National Health and Medical Research Council and Multiple Sclerosis Research Australia. The researchers used several repositories to complete these experiments – the Accelerated Cure Project for MS, The Human Brain and Spinal Fluid Resource Center (which is sponsored by the National MS Society, among others), and the Tasmanian MS Longitudinal Study.

Advertisements

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

 

New Lab Studies Add Evidence That High Salt Diets Increase Inflammation and May Have Implications for MS

Summary
• The results from two recently published laboratory studies suggest that high levels of salt shift the balance of the immune system toward inflammation, and that salt alters the function of several types of immune cells pertinent to MS.
• These two studies, which were both published in the Journal of Clinical Investigation, were led by Dr. David Hafler (Yale University) and Dr. Dominik Müller (Max-Delbruck Center, Berlin, Germany).
• Dr. Hafler is funded by the National MS Society to study the impact of high salt on the immune system, and the Yale team is also conducting a pilot clinical trial to explore the impact of high- and low-salt diets on MS disease activity.

Background: Eating high levels of salt, which is part of the typical Western diet, has been linked to heart disease, chronic inflammation, and cancer. Recent lab reports have also suggested that dietary salt can speed the development of the immune attack in an MS-like disease in mice, and that the mouse disease responds differently to salt depending on the gender and genetic makeup of the mice. One small study in people found a possible link between dietary salt levels and relapses in people with MS, but this study suggested a link, which is not the same as establishing an actual cause. So far, laboratory findings related to the effects of salt have been stronger than the few studies that have been reported in people. Understanding whether high dietary salt is a risk factor for developing MS or for worsening disease activity is an active area of research.

The Studies: Two studies recently published in the Journal of Clinical Investigation suggest that high dietary salt affects two types of immune cells in a way that increases inflammation, a state that is generally considered harmful in MS. A study by National MS Society-supported researchers at Yale University and Harvard Medical School led by David Hafler, MD, investigated the effects of high salt on regulatory immune cells called “Tregs.” Tregs normally suppress immune responses by other immune cells, but in people with MS Tregs have been shown to be less able to perform this helpful function to turn off attacks. The team showed in mice and in cells in lab dishes that high salt blocks the ability of Tregs to suppress potentially harmful immune cells, and shifts Tregs toward activity that increases inflammation.

The other study, by an international team led by Dominik N. Müller at the Max-Delbruck Center in Berlin, Germany, investigated immune cells called “macrophages.” This study showed that high salt blocks the activation of a subset of macrophages, reducing their ability to suppress inflammatory cells and creating an imbalance in the immune system. In mouse models, high salt diets also delayed wound healing.

Comment: Taken together, these laboratory studies add new evidence that high levels of dietary salt may increase inflammation and autoimmunity, and decrease the ability of regulatory cells and processes to limit harmful immune cell activity. More studies are needed to determine the possible role of a high-salt diet in the risk of developing MS and whether reducing salt intake may be helpful for reducing disease activity in people with MS. Dr. Hafler is funded by the National MS Society to study the impact of high salt on the immune system, and the Yale team is also conducting a pilot clinical trial to explore the impact of high- and low-salt diets on MS disease activity.

Read more about dietary factors that may play a role in MS
Read more about research on the immune system in MS

Scientists fault gene mutation for inflammation

A new mouse model study has identified a faulty “brake” within immune cells, one that should control inflammation, and points to a potential target for developing new therapies to treat multiple sclerosis. The results suggest new research models of multiple sclerosis symptoms such as movement disorders and balance control problems.
A mutation in the gene Nlrp12 was causing a malfunction in T cells. Normally, the protein the gene produces acts as a brake within T cells to control the inflammatory response. But a mutation in that gene disrupts the natural process and provokes severe inflammation. The resulting inflammation produced MS symptoms such as movement disorders and problems with balance control.
Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, according to researcher John Lukens, Ph.D., of the University of Virginia School of Medicine, “It’s important to note that MS is a spectrum disorder – some patients present with paralyzing conditions and some patients don’t. Not everybody’s symptoms are the same, so this might give us a glimpse into the etiology or pathogenesis of that family of MS.”

Researchers implicate chemical in MS

A new study confirms that the cytokine granulocyte macrophage colony-stimulating factor (GM-CSF) likely plays an important role in multiple sclerosis. Researchers also offer a new explanation for why the MS treatment interferon-Beta (INF-β) is often effective at reducing attacks.

Researchers, led by Abdolmohamad Rostami, M.D., Ph.D., Chair of the Department of Neurology at Thomas Jefferson University and director of its neuroimmunology laboratory, tested blood samples of patients with MS who had not yet received therapy, and those currently being treated with INF-β, a commonly used therapy. On average, untreated patients had two to three times as many immune cells producing GM-CSF as did patients being treated with INF-β, or normal subjects. Researchers looked at brain samples of deceased patients with MS and found increased numbers of GM-CSF-producing cells in comparison to normal brain samples.

“Abundant GM-CSF production at the sites of CNS inflammation suggests that GM-CSF contributes to MS pathogenesis. Our findings also reveal a potential mechanism of IFN-β therapy, namely suppression of GM-CSF production,” the authors said.

The findings were published online in the Journal of Immunology.

New molecule may lead to inflammation inhibitor

Scientists have developed a new drug-like molecule that can inhibit inflammation. The find has shown promise in preventing the progression of multiple sclerosis.
Walter and Eliza Hall Institute scientists have developed a small drug-like molecule called WEHI-345 that binds to and inhibits a key immune signaling protein called RIPK2. This prevents the release of inflammatory cytokines. Examining WEHI-345’s potential to treat immune diseases in experimental models of MS, it was found that WEHI-345 prevented further progression of the disease in 50 percent of cases after symptoms of MS first appeared.
Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. Calling the results extremely important, researchers said WEHI-345 had potential as an anti-inflammatory agent.
The study’s lead author, Dr Ueli Nachbur, said institute scientists would use WEHI-345 to further investigate the signaling pathway that produced inflammatory cytokines and to develop a better, stronger inhibitor of RIPK2 for treating inflammatory disease. “This signaling pathway must be finely balanced, because WEHI-345 only delayed signaling rather than blocked it. Nevertheless, this delay is enough to completely shut off cytokine production,” he said.
The research was published in the journal Nature Communications.

Post Navigation