disease progression

I have been contemplative these last few days, lost in thought regarding the state of the MS. I am not sad or upset, simply in observation mode. Reaching for what may have precipitated this gentle melancholy, I realize I am on the precipice of my 49th year. While MS continues…

Degeneration of the brain’s deep gray matter is associated with more rapid disability in multiple sclerosis patients, a European study shows. The research, “Deep gray matter volume loss drives disability worsening in multiple sclerosis,” was published in the journal Annals of Neurology. Scientists know that loss…

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 “…

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…

  They say a near-death experience will invoke a montage of your life in a matter of seconds. Gratefully, I have not had the experience to find out if this is indeed a truism, but I recently experienced a mini-mélange of my own. I read the mail, more specifically the…

Blood levels of the nerve damage marker neurofilament light provide a reliable picture of multiple sclerosis activity in both the relapsing-remitting and progressive forms of the disease, a Swedish study reports. The University of Gothenburg researchers also discovered a close link between its levels in blood and spinal fluid. This means the…

Sweden's Active Biotech said its experimental therapy Laquinimod failed to meet the primary and secondary objectives of Phase 2 clinical trial evaluating the drug's potential to treat primary progressive multiple sclerosis. Laquinimod, also known as Nerventra or ABR-215062, was developed by Active Biotech and Israel's Teva Pharmaceutical Industries. The drug targets inflammation and degeneration in neurological tissue. Preclinical studies using animal models of multiple sclerosis showed that laquinimod regulated inflammatory and immune responses in these animals, reducing disease progression. The ARPEGGIO Phase 2 study aimed to evaluate laquinimod's efficacy, safety and tolerability in PPMS patients. Its primary endpoint was brain atrophy as defined by percent brain volume change. Secondary goals included time to disability progression, change in timed 25-foot walk, and number of new T2 lesions. The multicenter, randomized, double-blind, placebo-controlled trial enrolled 374 individuals. Initially, the study aimed to evaluate two doses of laquinimod — 0.6 and 1.5 mg/day — in PPMS compared to placebo. However, the highest dose was discontinued in January 2016 after some participants reported adverse cardiovascular events. In a Dec. 1 press release, Active Biotech said the lower dose of laquinimod failed to slow both the rate of brain atrophy and disease progression. “There was, however, a reduction in new T2 lesions observed in patients treated with laquinimod 0.6 mg,” said the company's president and CEO, Helén Tuvesson. The trial revealed a similar safety profile to that observed in previous studies in relapsing-remitting MS patients (RRMS). The most common adverse reactions were headache, nasopharyngities, upper respiratory tract infection,and back pain. Results of the ARPEGGIO trial will likely be presented at a future scientific conference and published in a scientific journal. Earlier this year, Active Biotec stopped developing laquinimod as a potential RRMS treatment after a Phase 3 study failed to achieve its primary goal: slowing disease progression. Laquinimod is also being evaluated as a potential therapy for Huntington’s disease in a Phase 2 clinical trial.

MMJ BioScience, an affiliate of medical cannabis research company MMJ International Holdings, has hired a principal investigator to lead clinical trials exploring potential therapeutic applications of cannabinoids in progressive multiple sclerosis (MS). Dr. Bianca Weinstock-Guttman, a neurology professor at the State University of New York at Buffalo, is executive director…

After the first round of symptoms, multiple sclerosis can stay mild without causing major problems for decades, a 30-year British study indicates. Karen K. Chung of the University College London Institute of Neurology discussed the findings at the ECTRIMS-ACTRIMS meeting in Paris, which started Oct. 25 and runs until 28. His presentation was titled “Does…

Two short courses of Lemtrada prevented multiple sclerosis from becoming active and progressing for five years, a study reported. Lemtrada's maker, Sanofi-Genzyme, said the study covered the two-year CARE-MS II Phase 3 clinical trial (NCT00548405) and a long-term extension (NCT00930553) trial of people with relapsing-remitting MS. In addition to demonstrating Lemtrada's effectiveness, the study showed that it was safe, researchers said. The Phase 3 trial participants had had an active disease, with at least two relapses in the two years before the study and an inadequate response to earlier treatment. The trial compared Lemtrada's effectiveness with that of Rebif. The Lemtrada group received 12-mg doses for five consecutive days at the start of the study and three consecutive days a year later. Ninety-three percent of the 435 patients who completed the trial enrolled in the extension, which followed patients for another three years. Remarkably, 60 percent of patients required no additional treatment after the two years of the Phase 3 study. Among the 376 patients who required more treatment, 30 percent had one additional Lemtrada course, 10.4 percent had two, and 1.6 percent had three. A small proportion of patients also received other disease-modifying treatments. The most common reason for additional treatment was relapse. Nevertheless, Lemtrada reduced annualized relapse rates to only 0.18 of patients by the fifth year. In addition, during the five years, 75 percent of patients experienced no worsening of their disability over six-month cycles. And 49 percent of patients' disability improved. Researchers also tracked patients' scores on the NEDA — or No Evidence of Disease Activity — index. The composite measure takes into account relapses, disease activity detected in MRI scans, and disability progression. In year five, 58 percent of patients achieved NEDA, slightly more than the 53 percent in year three. Another important finding was that patients' loss of brain tissue slowed in the first two years, and dropped further during the extension. Researchers also noted that adverse events dropped during the extension trial. Ninety-six percent were mild or moderate, and no patient left the study because of side effects. The rate of infusion-associated reactions was lower in the extension study than in the Phase 3 study. Patients who did have a reaction most often experienced headache, fever, or rash. Infections did not become more common with accumulating Lemtrada doses and, again, were less common in the extension trial. Patients most often developed colds or urinary tract infections. Autoimmune reactions against the thyroid gland were relatively common, however. Thirty-eight percent of patients developed them over the five years. Most were moderate in severity. Four patients developed various types of cancers. Researchers also examined Lemtrada in the CARE-MS I clinical trial and its extension trial. They reported long-term outcomes and safety findings similar to those in the latest study. Overall, the newest results demonstrated that Lemtrada slowed disease progression over five years in relapsing-remitting MS patients who failed to respond to previous therapy.

Fast Forward, a non-profit subsidiary of the National Multiple Sclerosis Society, will give financial support to TG Therapeutics to advance TGR-1202 (umbralisib) into preclinical testing as a potential oral therapy for progressive forms of multiple sclerosis. The support, whose value was not specified, is part of a Sponsored Research Agreement between Fast Forward and the company. Research work will be led by Lawrence Steinman, MD, a professor of pediatrics, neurology, and neurological sciences at Stanford University. TGR-1202 is an orally administrated inhibitor that blocks a signaling enzyme called PI3K delta. Immune cells such as B-cells have high levels of this enzyme, which is thought to be important for cell proliferation and survival. "We look forward to evaluating umbralisib [TGR-1202]'s effect on our preclinical progressive MS models in hopes to move umbralisib closer to clinical development in MS," Steinman said. The approval of Ocrevus (ocrelizumab), by Genentech, to treat primary progressive and relapsing multiple sclerosis underscored the potential of B-cell-targeted therapies for MS patients. As a result, investigative drugs that also aim to bolster B-cell survival or activity, such as those being developed by TG Therapeutics, are an attractive approach to potentially treating patients. Another potential treatment by the company — an engineered antibody, TG-1101 — targets a specific sequence on the CD20 protein found on immune B-cells. This infusion therapy is now in two Phase 3 clinical studies for relapsing multiple sclerosis, ULTIMATE I and ULTIMATE II. Both are currently enrolling patients at sites in Kentucky, Tennessee, and New York.

Sometimes walking, even with an assistance device, can be very challenging because of the extreme muscle weakness that I experience. The slow, off-balanced gait that has been my constant companion for many years prior to my 2010 multiple sclerosis (MS) diagnosis is definitely on the decline. Accepting the…

A five-year study demonstrated that Sanofi-Genzyme’s Lemtrada (alemtuzumab) provides long-term benefits for relapsing-remitting multiple sclerosis patients, reducing relapse rates and preventing the progression of the disease. Importantly, most patients required only the standard two-phase treatment course. Few needed additional courses because of relapse or new brain lesions. The study,…

Two molecules known to regulate cellular signaling contribute to the underlying mechanism of progressive multiple sclerosis, found a recent study conducted by investigators at Oregon Health & Science University and Yale University School of Medicine. These two proteins are related to each other, as they participate in the same cellular signaling process that regulate the immune system's response. Previous studies have blamed them for the worsening of several autoimmune and inflammatory disorders including rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosus. The research team found that patients with progressive MS had higher levels of MIF and D-DT proteins than those with the relapsing-remitting form of the disease. In addition, these proteins inflamed the central nervous system, making patients sicker. An analysis of the genes that encode the proteins revealed that higher levels of MIF were linked to the presence of two genetic variants that are more frequent in patients — particularly males — with progressive disease. Researchers confirmed their findings with animal models of MS-like disease that were genetically engineered to lack MIF and D-DT proteins. Taken together, this finding suggests that a simple genetic test could identify patients carrying the MIF genetic susceptibility — and therefore more likely to develop a severe form of MS. This study was partially funded by the National Institutes of Health, the National Multiple Sclerosis Society, the Rocky Mountain MS Center Tissue Bank and the U.S Department of Veterans Affairs.

Disarm Therapeutics has completed the first round of financing to develop a compound that prevents axonal degeneration in patients with multiple sclerosis (MS) and other neurodegenerative conditions. The treatment approach is based on an earlier discovery at Washington University in St. Louis, showing that the enzyme SARM1…