Patricia Inacio, PhD, science writer —

Blood stem cell transplants lead to significant improvements in relapsing-remitting multiple sclerosis patients’ disability, a Phase 3 clinical trial shows. The 110 patients who took part in the MIST study (NCT00273364) were having relapses after receiving standard therapies such as beta interferon, Copaxone (glatiramer acetate), Novantrone (mitoxantrone), Tysabri (natalizumab), Gilenya (fingolimod),…

Since Genentech‘s Ocrevus was approved a year ago, the treatment rate of primary progressive multiple sclerosis (PPMS) has increased significantly. However, a closer look at the data shows that other disease-modifying therapies (DMTs) are equally responsible for this increase. The findings were reported by Spherix Global Insights in their new study…

Merck KGaA’s evobrutinib led to significant reductions in relapsing multiple sclerosis patients’ brain and spinal cord lesions, compared with a placebo, a Phase 2b clinical trial showed. Researchers measured the number of lesions at weeks 12, 16, 20 and 24. Evobrutinib, also known as M2951, is an oral inhibitor of…

One way the body may protect itself from nerve cell inflammation is to have cells in the blood-brain barrier increase their production of a protein that keeps immune cells from entering the brain, researchers in Germany and Canada report. The finding suggests that scientists could develop a multiple sclerosis therapy around the protein, known as EGFL7. It would work by preventing as many inflammation-generating immune cells from entering the brain. The underlying trigger for MS is immune cells crossing the blood-brain barrier to invade the central nervous system (CNS). The barrier is a selective membrane that shields the CNS from general blood circulation. Therapies that prevent immune cells from entering the brain can help control the disease, studies have shown. They include Tysabri (natalizumab, marketed by Biogen). But “as with other highly effective disease-modifying therapies which influence a broad range of peripheral immune cells, potential devastating adverse events limit the use of this therapy as a first-line agent,” the researchers wrote. The team at Mainz University Medical Center in Germany and the University of Montreal wondered if epidermal growth factor-like protein 7 (EGFL7) could prevent the brain inflammation in MS.  Although scientists had not previously linked it to MS, it was shown to regulate the migration of immune cells into breast cancer tumors. The CNS response to the chronic inflammation seen in MS patients and a mouse model of the disease was to increase EGFL7 in the blood-brain barrier, the researchers found. Researchers said the increase prevented pro-inflammatory immune cells from crossing into the CNS. Endothelial cells that line blood capillaries in the blood-brain barrier are the ones that secrete EGFL7. “We postulate that EGFL7 upregulation by BBB-ECs [brain blood barrier-endothelial cells] is induced as a compensatory mechanism to promote survival and recovery of BBB function in neuroinflammatory conditions,” the team wrote. Researchers then tested what happened in mice that lacked EGFL7. They found that the mice developed MS earlier and that their blood-brain barrier membrane was less efficient at keeping immune cells out. Treatment with EGFL7 improved the disease severity in the MS mice and tightened the blood-brain barrier, they said. “In light of our findings, smaller EGFL7 agonists, in development for other diseases, could therefore constitute an appealing therapeutic avenue for MS,” the team concluded.

Inhibiting an oxidative stress enzyme reduced nerve cell damage and promoted the formation of new nerve cells, a multiple sclerosis study in mice showed. It also helped regenerate cells that produce the nerve cell-protecting myelin sheath, researchers said. The team used a mouse model of the progressive form of MS in…

Reprogramming skin cells into brain stem cells, then transplanting them into the central nervous system may reduce inflammation and reverse the nerve cell damage in progressive multiple sclerosis, a mouse study shows. Scientists have dubbed macrophages the immune system's big eaters because they engulf abnormal cells like cancer in addition to invaders like viruses and bacteria. Special classes of macrophages live in a number of organs, including the brain and spinal cord, where they’re called microglia. Although they protect the body, microglia can participate in the development of progressive forms of MS by attacking the central nervous system, causing nerve cell damage. MS is an autoimmune disease, or one in which the immune system can attack healthy tissue besides invaders. Recent studies have suggested that neural stem cells, which have the capacity to differentiate into any type of nerve cell, can regulate immune response and inflammation in the central nervous system. At one point, researchers obtained neural stem cells from embryos. But this technique generated only a fraction of the cells needed for treatments. Meanwhile, doctors have tried to avoid collecting stem cells from someone with a different genetic profile than the patient because this increases the risk that the immune system will attack them once they're transplanted. University of Cambridge scientists decided to try reprogramming skin cells into neural stem cells. The idea behind the mouse study was that using skin cells from the same person who will receive the stem cells will reduce the chance that the immune system will attack the stem cells. In the mouse study, the team discovered a link between higher than normal levels of a small metabolite, called succinate, and chronic MS. The metabolite prompts macrophages and microglia to generate inflammation in the cerebrospinal fluid that bathes the brain and spinal cord. Transplanting neural stem cells and progenitors of these stem cells into the cerebrospinal fluid of mice improved the animals' chronic nerve cell inflammation. The stem cells reduced the animals' succinate levels and switched their macrophages and microglia from a pro- to an anti-inflammatory state. This led to a decrease in inflammation and less damage to the central nervous system. “Our mouse study suggests that using a patient’s reprogrammed cells could provide a route to personalized treatment of chronic inflammatory diseases, including progressive forms of MS,” Stefano Pluchino, a principal researcher in Cambridge's Department of Clinical Neurosciences, said in a press release. “This is particularly promising as these cells should be more readily obtainable than conventional neural stem cells and would not carry the risk of an adverse immune response,” said Pluchino, the study's lead author. Luca Peruzzotti-Jametti, a Wellcome Trust research training fellow, said the discovery would not have been possible without a multidisciplinary collaboration. “We made this discovery by bringing together researchers from diverse fields, including regenerative medicine, cancer, mitochondrial biology, inflammation and stroke, and cellular reprogramming."

Ocrevus (ocrelizumab), Genentech’s humanized anti-CD20 monoclonal antibody, continues to show clear evidence that it helps to slow disease progression and enable better function — including in the hands and limbs — of relapsing multiple sclerosis (MS) and primary progressive multiple sclerosis (PPMS), latest data reveals. The first FDA-approved therapy — in March…

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.

Pregnant women with multiple sclerosis (MS) exposed to Tysabri (natalizumab) in the first trimester had higher rates of miscarriage and major birth defects in their babies, than women left untreated or treated with interferon beta, a study shows. Although higher, these rates were similar to those in the general…

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…

Multiple sclerosis (MS) patients who experience a relapse after two courses of Lemtrada (alemtuzumab) treatment showed improvements in relapse rate and disability after a third Lemtrada course, according to results of the CARE-MS II trial extension. The poster reporting the findings, titled “Efficacy of Alemtuzumab Retreatment in Patients Who Experienced Disease Activity after…

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 “…

The walking speed of multiple sclerosis patients taking Adamas Pharmaceuticals’ ADS-5102 (amantadine) increased by 16.6 percent more those taking a placebo, a Phase 2 clinical trial reports. Another finding was that more of the treated patients increased their walking speed by 20 percent or more during the four-week trial. The study,…

Extending the dosing periods of Tysabri (natalizumab) treatment may help reduce the risk of progressive multifocal leukoencephalopathy, or PML, in multiple sclerosis (MS) patients infected with the JC virus, a study suggests. The study, “Natalizumab Extended Interval Dosing Is Associated with a Reduction in Progressive Multifocal Leukoencephalopathy…

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,…

When choosing between the single use autoinjector Rebif Rebidose or the reusable autoinjector Rebiject II, patients with relapsing-remitting multiple sclerosis (RRMS) found both easy to very easy to use, according to the results of a study. A higher number of the patients reported a preference for the single-use autoinjector…

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…

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."

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,…

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…

New research shows how a high-salt diet leads to excessive levels of interleukin-17 (IL-17) in multiple sclerosis (MS) patients, causing changes in endothelial cells that result in dementia. These findings suggest that therapeutics targeting IL-17 may help halt the neurovascular damages of MS and other autoimmune diseases linked to high…

The approved lymphoma therapy Rituxan (rituximab) has shown promise as a treatment for  multiple sclerosis. A new study indicates the Genentech treatment is effective and safe against neurological diseases like MS for up to seven years. The research, “Long-term safety of rituximab induced peripheral B-cell depletion in…

Iranian researchers have identified another herpes virus that may increase the risk of a person developing multiple sclerosis. The team identified the human herpesvirus 6, or HHV6, as a potential risk factor for MS through a meta-analysis of several studies. They published their findings, “Relationship of Human…

Researchers at GlaxoSmithKline (GSK) have identified the histamine receptor 3 (H3R) as a potential new therapeutic target for promoting remyelination in patients with multiple sclerosis (MS). Their study “Histamine Receptor 3 negatively regulates oligodendrocyte differentiation and remyelination,” appeared in the journal PLOS One. Regrowth of myelin is known as…

Treatment with Gilenya (fingolimod) may limit cerebral gray matter atrophy in relapsing-remitting multiple sclerosis (RRMS) patients, researchers at Boston’s Brigham and Women’s Hospital have found. Their report, “A two-year study using cerebral gray matter volume to assess the response to fingolimod therapy in multiple sclerosis,” appeared in the…

Clomipramine, an approved antidepressant, shows potential in treating people with progressive multiple sclerosis (MS)  — a disease form with few treatments — by protecting nerves from various processes thought to underly progressive MS, early research shows. The lab and animal study, which focused on already-approved treatments, was titled “Systematic…

Zinbryta (daclizumab) may not be the best follow-up therapy for relapsing–remitting multiple sclerosis patients who stop taking Tysabri (natalizumab) for safety reasons, a case study suggests. An article on the 25-year-old patient’s case, titled “Disease reactivation after switching from natalizumab to daclizumab,” was published in…

Multiple sclerosis patients with additional diseases, high cholesterol levels or a history of migraine headaches are more likely to experience relapses than other patients, a Canadian study shows. The report, “Comorbidity increases the risk of relapse in multiple sclerosis,” was published in the journal Neurology. Researchers…

Researchers further explored how our internal biological clock — known as circadian rhythm — influences immune system responses. Disruptions to that rhythm are associated with immune diseases like multiple sclerosis (MS), although in ways not fully understood and, the study suggests, may affect response to treatment. A natural 24-hour cycle that exists…