News

February 2, 2018 News by Patricia Inacio, PhD

#ACTRIMS2018 – MediciNova Presents Positive Results from SPRINT-MS Trial Evaluating Ibudilast in Progressive MS

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,…

February 2, 2018 News by Patricia Silva, PhD

#ACTRIMS2018 – Relapsing MS Patients With Impaired Vision Improved on Ocrevus, Updated Trial Data Show

Ocrevus improved vision among relapsing multiple sclerosis patients who participated in the Phase 3 clinical trials of the treatment, according to updated analyses recently presented at the ACTRIMS Forum 2018. While Ocrevus-treated patients improved their ability to read low-contrast letters over the course of the two trials, people who received Rebif (interferon beta-1a) did not. Laura J. Balcer, a neurologist at New York University Langone Medical Center, shared the data in a presentation titled, “Effect of Ocrelizumab on Visual Outcomes in Patients with Baseline Visual Impairment in the OPERA Studies in Relapsing Multiple Sclerosis.” Balcer had earlier shared data on the visual outcomes of relapsing patients in the OPERA I and OPERA II Phase 3 clinical trials of Ocrevus at the 7th Joint ECTRIMS-ACTRIMS Meeting in Paris, last year. The two studies — sponsored by Ocrevus developer Genentech, a member of the Roche group —  compared Ocrevus and Rebif in patients with relapsing MS. This time, her presentation focused only on patients who had visual impairment when they enrolled in the trials. Among a total of 1,656 participants, 375 of those treated with Ocrevus and 373 in the Rebif group had visual impairment. Researchers tested vision using a low-contrast letter acuity test. The test is similar to an ordinary vision test, with letters of different sizes on a chart. But the low-contrast test uses gray letters — instead of black — on a white background. Researchers included charts with two shades of gray to test different contrast levels. These tests can detect reduced visual function. At the beginning of the trials, both groups performed in a similar manner — correctly identifying about 35 letters on a chart with somewhat higher contrast. After 96 weeks, those receiving Ocrevus identified on average 3.4 more letters, while Rebif-treated patients worsened by 0.5 letters — a significant difference, Balcer said. Researchers tested vision every 12 weeks. At the end of the trials, they found that 39 percent more patients in the Ocrevus groups had a cumulative improvement of at least 10 letters, compared to those treated with Rebif. At this time, 26.4 percent of Ocrevus-treated patients improved 10 letters or more, compared to 19.8 percent in the Rebif group. The difference between the groups for at least seven letters was 54 percent, with Ocrevus-treated patients performing better. Researchers believe that a seven-letter change is the minimal clinically important difference for the test. Based on the results, researchers believe that the findings demonstrate Ocrevus’ ability to reverse visual impairment in relapsing MS. The ACTRIMS Forum 2018 is being held in San Diego, California, Feb. 1–3.

January 31, 2018 News by Patricia Inacio, PhD

#ACTRIMS2018 – Oryzon Enrolls First Patient in SATEEN Trial, Presents New Data at MS Meet

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."

January 29, 2018 News by Alice Melão, MSc

Registrations Open for Upcoming Nashville CMSC 2018 Meeting

Registrations are now open for the 32nd Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC), set for May 30-June 2 at the Music City Center in Nashville, Tennessee. The CMSC Annual Meeting is the nation’s largest educational conference and professional development event for healthcare practitioners, researchers and…

January 26, 2018 News by Patricia Silva, PhD

Easing Blood Flow in Neck Reduces Headaches, Fatigue in Certain MS Patients, Study Shows

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.

January 25, 2018 News by Alice Melão, MSc

Non-invasive Brain Stimulation Reduces MS-associated Cognitive Fatigue

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…

January 24, 2018 News by Patricia Inacio, PhD

MS Patients’ High Osteopontin Protein Levels Make It a Potential Biomarker for the Disorder, Study Reports

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."

January 24, 2018 News by Alice Melão, MSc

Study Identifies MS Patients at Risk of Severe Disease Reactivation After Gilenya Is Discontinued

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."  

January 17, 2018 News by Patricia Silva, PhD

Trial to Evaluate H.P. Acthar Gel Is Enrolling Patients with Relapsing-remitting MS

Mallinckrodt Pharmaceuticals is seeking 66 participants for a clinical trial to determine the safety and effectiveness of its injected therapy H.P. Acthar Gel as a treatment for acute relapses in people with relapsing-remitting multiple sclerosis (RRMS). MS relapses are flare-ups of central nervous system inflammation that damage the myelin coating that protects nerve cells. The damage disrupts the transmission of impulses between the cells, causing spikes in MS symptoms. For severe relapses that interfere with a person’s mobility, safety or ability to function, most neurologists recommend corticosteroid treatment administered intravenously or taken orally. Steroids can also be administered by injection of a gel under the skin. H.P. Acthar Gel is designed to provide extended release of steroids in the body. The trial will evaluate whether the gel is an effective treatment for RRMS patients who have been unable to recover from a relapse after receiving high-dose intravenous or oral steroids. Researchers will randomly assign participants to receive either H.P. Acthar Gel or a placebo, delivered by injection once a day for 14 days. Follow-up visits will be required at 14, 28 and 42 days. The study's main objective will be seeing whether patients' disability improves. Researchers will use a standard tool for measuring disability known as the Expanded Disability Status Scale.  Other objectives will include seeing how the therapy affects patients' fatigue, quality of life, workplace productivity, and use of healthcare resources. Participants must have a confirmed diagnosis of RRMS, be older than 18 years of age, and have experienced a relapse within 29 days of enrolling in the trial. For more information about enrollment criteria and how to participate in the trial, please contact Valerie Carvajal at (800) 556-3314 or by email at [email protected]. The National Multiple Sclerosis Society announced in an MS trial alert that Mallinckrodt will be  enrolling participants in Tucson; Fort Collins, Colo.; Tampa; Atlanta; Savannah, Ga.; Northbrook, Ill.; Fort Wayne, Ind.; Indianapolis; Kansas City, Kan.; New York; Cleveland; Dayton, Ohio; Dallas; Round Rock, Texas; San Antonio; Salt Lake City; Richmond, Va.; and Tacoma, Wash. Without clinical trial participation there is no way for patients to obtain new medicines or for scientists to ultimately find a cure for MS. The National MS Society encourages participation. It has developed a guide for patients who want to take part in studies called “Participating in Clinical Trials.” It covers the basics of participation, benefits versus risks, patient protection, costs and other important issues about trials.  

January 16, 2018 News by Jose Marques Lopes, PhD

Myelin Loss Can Be Assessed With Innovative Imaging Approach, Study Suggests

A novel imaging approach enables assessment of key nervous system deterioration in multiple sclerosis (MS), a new study in mice suggests. The research, “Development of a PET radioligand for potassium channels to image CNS demyelination,” was published in the journal Scientific Reports. MS is characterized by damage to myelin (a process called demyelination), which is an insulating sheath around axons (the long projections of neurons) that enables effective neuronal communication. As a result, patients experience a variety of symptoms, including muscle stiffness and weakness, fatigue and pain. Although existing MS medications suppress immune responses and reduce flare-ups, none can cure the disease. Despite the importance of demyelination in MS, scientists and clinicians do not currently have a way to directly image myelin damage. Magnetic resonance imaging (MRI) is used, but it does not enable the distinction between demyelination and inflammation, which are common in patients with MS. Upon myelin damage, voltage-gated potassium channels (cellular membrane proteins) become exposed. As a result, cells leak potassium, which impairs proper neuronal communication. This prompted researchers to develop a tracer that targets potassium channels. "In healthy myelinated neurons, potassium channels are usually buried underneath the myelin sheath," Brian Popko, PhD, the study’s senior author, said in a press release. Popko is a professor of neurological disorders and director of the Center for Peripheral Neuropathy at The University of Chicago. Exposed potassium channels can be targeted by the MS medication 4-aminopyridine (4-AP; dalfampridine), which partially repairs nerve conduction and mitigates MS symptoms. Using mouse models of MS, the researchers demonstrated that 4-AP binding to potassium channels is greater in demyelinated axons in comparison with well-myelinated axons. The greater binding of 4-AP led to its accumulation in damaged axons. Then, the team evaluated several fluorine-containing derivatives of 4-AP, and found that the most effective in binding to potassium channels was 3-fluoro-4-aminopyridine (3F4AP), which can be labeled with radioactive 18F. This labeling enables detection of demyelinated regions with a novel strategy based in positron emission tomography (PET). "3F4AP is the first tracer whose signal increases with demyelination, potentially solving some of the problems of its predecessors," said Pedro Brugarolas, PhD, first author of the study. Existing PET tracers bind to myelin. This translates to decreases in signal in the presence of myelin loss, “which can be problematic for imaging small lesions” Brugarolas noted. Importantly, the findings in mice were confirmed in monkeys. Experiments showed that the radiolabeled 3F4AP enters the primate brain and accumulates in areas with less myelin. Collectively, “these data indicate that [18F]3-F-4-AP may be a valuable PET tracer for detecting [central nervous system] demyelination noninvasively,” the team wrote. "We think that this PET approach can provide complementary information to MRI which can help us follow MS lesions over time," Popko said. The novel PET strategy enables the evaluation of therapies to repair myelination and also could help assess how much myelin loss is involved in other neurological disorders, such as traumatic brain injury and spinal cord injury, but also in diseases not commonly linked to demyelination, "such as brain ischemia, psychiatric disorders, and neurodegenerative diseases, including Alzheimer's," Popko concluded.

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