research

University at Buffalo researchers are working on ways to improve multiple sclerosis patients’ cognitive function and to repair damage to the mylein coating that protects nerve cells. The National Multiple Sclerosis Society awarded the researchers more than $1.1 million to conduct the studies. One, “The Effects of Working Memory…

Inhibition of the neuroactive opioid growth factor (OGF) alters the blood levels of important pro- and anti-inflammatory proteins in mice with multiple sclerosis (MS)-like disease. The recognition of this regulatory response may represent a new way to monitor disease progression and treatment response in MS. These findings were reported in a study published in the journal Experimental Biology and Medicine, titled “Modulation of the OGF–OGFr pathway alters cytokine profiles in experimental autoimmune encephalomyelitis and multiple sclerosis.” The study was led by researchers at Penn State University. Understanding the underlying mechanisms involved in MS and finding ways to tackle them is crucial for improving early diagnosis, monitoring disease progression, and patient care. For many years, researchers at Penn State have been focused on understanding the benefits of low-dose naltrexone and its relation with OGF in health and disease, including MS. Naltrexone is marketed with the brand name ReVia, among others. This drug is used routinely off-label to treat MS and other autoimmune diseases, as it has demonstrated to it can reduce fatigue, lessen pain, and confer a general feeling of well-being to patients. Its mode of action is not fully understood, but it is known to block the interaction of the neuroactive OGF with its receptor OGFr. In addition, low-dose naltrexone and OGF were shown to prevent the proliferation of active immune cells in mice with MS-like disease. To further evaluate the role of OGF and low-dose naltrexone in MS, researchers treated mice with naltrexone and analyzed its impact on blood levels of pro- and anti-inflammatory signaling proteins (cytokines). Results showed that after 10 days, MS mice had increased levels in seven out of 10 tested cytokines. Treatment with OGF or low-dose naltrexone was found to specifically increase the levels of the pro-inflammatory IL-6 cytokine, and significantly reduce the levels of anti-inflammatory IL-10 protein. Two other pro-inflammatory proteins, TNF-α and IFN-γ, also were found to be increased in MS mice compared to healthy animals. While TNF-α levels were unaltered upon OGF or low-dose naltrexone treatment, IFN-γ was reduced at 10 days, but still present at higher-than-normal levels after 20 days of therapy. To validate its findings, the team analyzed the levels of the identified signaling proteins in blood samples collected from 14 MS patients and eight non-MS volunteers. Six MS patients were undergoing treatment with Copaxone (glatiramer acetate), and four of them had relapsing-remitting MS (RRMS). Four other RRMS patients and one primary progressive MS (PPMS) patient were receiving Copaxone plus low-dose naltrexone; three RRMS patients were receiving low-dose naltrexone alone. The analysis revealed that IL-10 serum values were comparable between non-MS controls and all MS patients on low-dose naltrexone alone, or Copaxone alone. Patients treated with both Copaxone and naltrexone presented a broad range of IL-10 serum values “that were significantly different from MS subjects receiving LDN [low-dose naltrexone] only,” the researchers wrote. In contrast, IL-6 cytokine was found to be significantly elevated in MS patients treated only with Copaxone compared to patients receiving low-dose naltrexone alone or together with Copaxone. “These data suggest that IL-6, a pro-inflammatory marker is very responsive to OGF and LDN therapy, and thus may be involved in other mechanistic pathways associated with the OGF-OGFr axis,” the researchers wrote. "Identification of inflammatory cytokines that have expression profiles mediated by OGF or LDN [low-dose naltrexone] therapy increase our panel of potential biomarkers for MS,” Patricia McLaughlin, PhD, said in a press release. McLaughlin is professor of neural and behavioral sciences at Penn State, and senior author of the study. “We hope that continued research will identify more specific cytokines and allow us to assemble a reliable panel of minimally invasive biomarkers related to the etiology and progression of MS," she added. Additional long-term human and mouse studies are needed to further evaluate if IL-6 and IL-10 are “appropriate markers to monitor progression of MS,” the researchers emphasized. Still, the team believes this study demonstrates that at least IL-6, IL-10, TNF-α, and IFN-γ, together with OGF, can be useful biomarkers to monitor MS. "McLaughlin and colleagues have researched OGF signaling for several decades, and this seminal discovery of dysregulation in OGF expression in MS patients, and animal models, is very exciting and could lead to prognostic biomarkers for this autoimmune disorder," concluded Steven R. Goodman, PhD, editor-in-chief of the journal in which the study was published.

Stem Cell Treatment Benefits Three-fourths of MS Patients in Phase 1 Trial This is encouraging news for MS patients hoping to see some action in the stem cell area. A Phase 1 mesenchymal stem cell trial is reporting positive results, and a Phase 2 trial is underway in…

The Accelerated Cure Project for Multiple Sclerosis and a Regeneron unit are teaming up to sequence the coding portion of genes in DNA samples of multiple sclerosis and other patients in the project’s repository. The cure project is a non-profit organization whose goal is to accelerate research to improve MS diagnosis and…

Inhibiting an enzyme responsible for turning genes on and off can reverse damage to the myelin sheath that protects nerve cells, improving limb function, a multiple sclerosis-related study in mice shows. The research, which involved mice with sciatic nerve damage rather than MS, was published in the journal Nature Medicine.

The idea that a vitamin D deficiency contributes to the risk of developing multiple sclerosis (MS) has been challenged in a recent study that examined subtle differences in a protein involved in vitamin D metabolism in people from different ethnic backgrounds. The study, “Vitamin D-Binding Protein…

A stem cell treatment improved the neurological symptoms of three-fourths of the multiple sclerosis patients in a Phase 1 clinical trial, New York researchers reported. The results prompted the team at the Tisch MS Research Center of New York to start a Phase 2 trial to further assess the therapy’s…

Deep-brain stimulation, a non-invasive way of targeting neurons in the cortex, can significantly ease symptoms of fatigue in multiple sclerosis (MS) patients, research drawn from a clinical trial suggests. These results, published in the journal Neurology: Neuroimmunology and Neuroinflammation, are in an article titled “Safety and preliminary efficacy of deep…

Australian researchers have identified the master regulator of the immune response signaling pathway that is out of sync in multiple sclerosis and other inflammatory diseases. The lynchpin in the process is the xIAP protein, the team said. Their discovery that it triggers the NOD2 pathway’s faulty inflammation signaling could lead to…

A combination of an anti-viral therapy and the anti-depressive mirtazapine can stop the worsening of an infection linked to the multiple sclerosis therapy Tysabri (natalizumab), a case study suggests. The infection, John Cunninghan polyomavirus, can cause a potentially fatal brain infection known as  progressive multifocal leukoencephalopathy, or PML. Both…

Ampyra (dalfampridine), approved to treat walking difficulties in multiple sclerosis (MS) patients, also helps with cognition and movement in the upper and lower extremities, according to a recent scientific presentation. These findings were reported at the 3rd Annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2018 in…

MedDay Pharma’s MD1003 leads to long-lasting improvements in progressive multiple sclerosis patients’ disability, a Phase 3 clinical trial follow-up study shows. Researchers presented the results at the third Annual Americas Committee for Treatment and Research in Multiple Sclerosis Forum in San Diego, Feb. 1-3. The poster presentation was titled “…

Clene Nanomedicine says its pre-clinical studies demonstrate the remyelination effects of CNM-Au8, supporting its potential to treat multiple sclerosis (MS) and other demyelinating disorders. Clene presented its data in a session, “Nanocrystalline Gold As a Novel Remyelination Therapeutic for Multiple Sclerosis,” that took place at the third annual Americas…

A specially tailored program focused on balance and eye-movement exercises can help multiple sclerosis (MS) patients improve balance, dizziness, fatigue, and quality of life, according to a…

Difficulties with walking and balance are common among people with multiple sclerosis and strongly affect their quality of life — even when disease progression may not be evident on scans or other measures of MS advance, according to research presented at a meeting last fall and recently reviewed by the National…

Top-line results from a clinical trial evaluating the investigational oral therapy ibudilast for progressive multiple sclerosis (MS) show that the therapy led to a significant reduction of brain atrophy in patients when compared to controls. Robert Naismith, MD, one of the study’s principal researchers from Washington University in St. Louis,…

Engaging all types of people for research isn’t just a nice thought. It is critical to obtaining research results that will be meaningful. Middle-aged white women are often the people who volunteer for studies. Men, young people, and most significantly, people of color, lack representation in studies. According…

The Phase 2a trial of GA Depot (glatiramer acetate) for the treatment of primary progressive multiple sclerosis (PPMS) has dosed the first patient, Mapi Pharma recently announced. In the U.S., Copaxone (glatiramer acetate injection, marketed by Teva Pharmaceutical) is the standard therapy for relapsing-remitting multiple sclerosis (RRMS), which is…

A molecule triggered by the male hormone testosterone protects male mice from developing multiple sclerosis, Northwestern Medicine researchers report. Their discovery may help explain why MS affects more women than men. It could also lead to targeted therapies to protect women against the disease. The study, “…

Oryzon Genomics has enrolled the first multiple sclerosis patient in its Phase 2a SATEEN clinical trial investigating the therapy ORY-2001. The Spanish company will also present new results from preclinical models of MS treated with ORY-2001 at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2018, set for Feb. 1-3 in San Diego. ORY-2001 is an epigenetic therapy, meaning it targets the expression and activity of genes. The drug inhibits two particular molecules, LSD1 and MAOB, and was previously shown to reduce cognitive impairment and neuroinflammation in preclinical models, including in a mouse model of MS — the experimental autoimmune encephalomyelitis (EAE) model. The therapy was also shown to have neuroprotective effects. During ACTRESS 2018, Oryzon's chief scientific officer, Tamara Maes, will present a poster, "ORY-2001 reduces inflammatory cell infiltration in the Theiler’s murine encephalomyelitis virus model and highlights the epigenetic axis in MS.” “In previous reports we showed that ORY-2001 reduces the clinical score, lymphocyte egress, immune cell infiltration and inflammation protecting the spinal cord from demyelination in a murine MS-EAE model,” Maes said in a press release. “Here we provide data on the efficacy of ORY-2001 in the Theiler’s murine encephalomyelitis virus model for multiple sclerosis." In a second poster, "ORY-2001 in multiple sclerosis: first clinical trial of a dual LSD-1/MAOB inhibitor,” Roger Bullock, Oryzon's chief medical officer, will detail the Phase 2a trial, SATEEN, testing ORY-2001 in patients with relapsing-remitting or secondary progressive MS over a 36-week period, followed by an open-label extension. “Our first patient enrolled in SATEEN signals a new landmark for the clinical development of this drug in different neurological indications,” said Bullock. “This is the first epigenetic approach in this disease, and we hope that it will contribute to enlarge and improve the therapeutic options for patients afflicted by MS."

TG Therapeutics‘ ublituximab (TG-1101) led to a remarkable reduction in multiple sclerosis patients’ brain and spine lesions, a Phase 2 clinical trial showed. In fact, none of the treated patients had new gadolinium-enhancing lesions — or damaged nerve cell areas — six months after treatment, researchers said. Their analysis covered patients…

Researchers have found a link between variations in two genes that control our 24-hour biological clock and the risk of a person developing multiple sclerosis. The study, “Association of circadian rhythm genes ARNTL/BMAL1 and CLOCK with multiple sclerosis,” was published in the journal PLOS ONE. Scientists know MS…

Removing obstructions in large neck veins reduced multiple sclerosis patients’ headaches for several years, British and Italian researchers have demonstrated. The magnitude and duration of the effect differed among patients with different types of MS, however. Researchers also found that the treatment reduced fatigue, particularly in relapsing-remitting (RR) MS patients.

One single session of non-invasive brain stimulation can reduce cognitive fatigue in patients with multiple sclerosis (MS), say researchers at Germany’s Otto-von-Guericke University Magdeburg. Their study, “Electrophysiological and behavioral effects of frontal transcranial direct current stimulation on cognitive fatigue in multiple sclerosis,” appeared in the…

Multiple sclerosis patients have high levels of a protein called osteopontin in their cerebrospinal fluid and blood, making it a potential tool for diagnosing the disease and predicting its course, a study suggests. The research, “Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis,” was published in the journal PLOS One. Researchers wanted to know if levels of osteopontin in cerebrospinal fluid and blood could be a reliable biomarker for MS. To arrive at answer, they “conducted a systematic review and meta-analysis" of studies that had measured the protein's levels in cerebrospinal fluid and blood "in MS patients and controls." The team searched for studies in three databases — PubMed, Web of Science and Scopus. Out of 27 that met their criteria, they used 22 in the meta-analysis. All four types of MS were represented in the studies — clinically isolated syndrome, relapsing-remitting MS, secondary progressive MS, and primary progressive MS. There were three types of controls in the articles — healthy people, people with non-inflammatory neurological disorders, and people with inflammatory neurological disorders. Researchers' first observation was that all of the MS patients had higher levels of osteopontin than controls. The protein's levels were significantly higher in relapsing-remitting MS patients than in those with clinically isolated syndrome, the group with the lowest osteopontin levels. Levels were similar in the other types of MS. Patients with an active disease had significantly higher levels of the protein in their cerebrospinal fluid than those with a stable disease. The results supported previous studies' findings that osteopontin levels are higher than normal in the cerebrospinal fluid and blood of MS patients, strengthening the notion that it could be used as a biomarker for MS. “Given the fact that OPN [osteopontin] levels are higher during relapses, we think that by monitoring this biomarker,  we might be able to predict the disease course," the team wrote. "We propose that developing drugs modulating OPN concentration may be a new treatment strategy for MS."

Multiple sclerosis patients with high relapse rates but less physical impairment before starting on  Novartis’ Gilenya (fingolimod) are likely to experience a surge in disease activity if they stop the treatment, researchers in Turkey report. The study, which dealt with patients with relapsing forms of MS, referred to the surge as "severe disease reactivation," or SDR. Researchers published their article, “Factors Predictive of Severe Multiple Sclerosis Disease Reactivation After Fingolimod Cessation,” in the journal The Neurologist. Studies have shown that Gilenya, which the U.S. Food and Drug Administration approved in 2010, can benefit adults with relapsing MS. It reduces annualized relapse rates and prevents more brain lesions from forming, compared with standard interferon treatments. Lesions are damaged nerve cell areas. Despite its benefits, Gilenya is not recommended for patients with heart or liver problems, low levels of white blood cells, severe herpes virus infections or other infections. Also, patients who do not respond to Gilenya and women who are planning to become pregnant are advised to stop the treatment. Discontinuing Gilenya can lead to a return to pretreatment disease activity, or severe disease reactivation, in some patients. It is unclear why this happens and why it affects only some patients. To better understand what risk factors could be associated with reactivation, a team at Istanbul University compared the demographic and disease features of patients who developed SDR after stopping treatment with Gilenya. SDR was defined as including these elements within 6 months of Gilenya discontinuation: more than 5 gadolinium-enhanced lesions or a tumefactive demyelinating lesion detectable by magnetic resonance imaging, the disease progressing to the point that additional treatment with methylprednisolone or plasma exchange was required, and progressive physical disability reflected by a 1-point or more increase in patients' scores on the Expanded Disability Status Scale, or EDSS, Thirty-one patients at the university’s MS clinic who had discontinued Gilenya were included in the study. Eight experienced SDR and 11 relapses. The mean time for SDR patients' reactivation to occur was 2.6 months, researchers said. Patients had significantly higher levels of lymphocytes — white blood cells involved in autoimmunity — than during Gilenya treatment. When the team compared the disease features of SDR and non-SDR patients, they found that SDR patients had significantly higher annualized relapse rates before starting Gilenya and lower EDSS scores. “A higher ARR [annualized relapse rate] is the major contributory factor toward development of SDR,” the researchers wrote. “Patients who had higher ARRs before fingolimod [Gilenya] treatment must be closely followed up both clinically and radiologically in terms of the early signs of severe reactivation,” they wrote. About 38 percent of the SDR patients failed to respond to steroid treatment. They received a plasma exchange, which led to moderate improvement in their condition. Based on this finding, the researchers suggested that “plasmapheresis [plasma exchange] must be considered in patients exhibiting steroid-refractory SDR.” "In conclusion, SDR may be observed within the first 3 months after cessation of fingolimod," the team wrote. "This may be explained by the rapid influx of lymphocytes into the CNS [central nervous system]. Patients with higher annualized relapse rates and lower Expanded Disability Status Scale scores before commencing fingolimod treatment were more likely to exhibit SDR."  

Non-Hispanic whites, especially females, are more likely to die from multiple sclerosis (MS) than any other racial group, though blacks tend to die earlier, concludes a study by researchers at the University of Southern California’s Keck School of Medicine. Their survey, “Multiple Sclerosis Mortality by Race/ Ethnicity, Age, Sex,…

A global collaboration of researchers led by Belgium’s Flanders Institute for Biotechnology has determined the structure of the pro-inflammatory cytokine IL-23 and its receptor IL-23R, which could be potential targets for treating multiple sclerosis (MS) and other autoimmune diseases. Their study, “Structural Activation of Pro-inflammatory Human Cytokine…

Multiple sclerosis patients with central nervous system pain have high levels of a protein known as nerve growth factor in their cerebrospinal fluid, a study shows. The research, “Nerve growth factor is elevated in the CSF of patients with multiple sclerosis and central neuropathic pain,” was published…

Deep grey matter volume loss in the brain drives multiple sclerosis (MS) progression and disability, and is particularly evident in people with progressive forms of the disease, a retrospective multi-center study suggests. The study “Deep grey matter volume loss drives disability worsening in multiple sclerosis” was published in…