disease progression

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 “…

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,…

Editor’s note: Tamara Sellman continues her occasional series on the MS alphabet with this column referencing terms starting with the letter P. This post comes fourth in a series of seven. Symptoms of MS Postural tremor Tremors (specifically, cerebellar tremors) are a common symptom of MS. A…

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…

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…

A diet rich in vegetables, fruits and whole grains may decrease symptoms and lessen disease progression in patients with multiple sclerosis (MS), a study suggests. The report, “Diet quality is associated with disability and symptom severity in multiple sclerosis,” appeared in the journal Neurology. “People with MS…

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.

So-called silent brain lesions in patients with early-stage relapsing-remitting multiple sclerosis (RRMS) may, in fact, not be silent at all, according to a French study that linked such lesions to cognitive decline in early MS. This link has likely been missed since the major tool for measuring disability in MS…

Exposure to certain gut bacteria at a young age may cause multiple sclerosis (MS) and fuel its progression, a new mouse study shows. The study, “Gut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood,” appeared in the journal Proceedings of the National…

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…

The generation of a thin myelin sheath during remyelination — one that continues to protect nerve cells over time — is indicative of the long-term health and activity of the central nervous system (CNS) in demyelinating diseases such as multiple sclerosis (MS), a new study shows. These findings, which aim…

Potential new ways of capturing disease progression in multiple sclerosis (MS) patients — including those with chronic as opposed to active inflammation — are coming to the fore as analyses continue into the huge amounts of data collected during pivotal clinical trials that led to Ocrevus’ approval, a leading Genentech researcher…

Aubagio (teriflunomide) can help to delay first clinical signs of multiple sclerosis (MS) from progressing to a definite diagnosis in a person, and treatment should likely begin as soon as that first episode is confirmed, Robert Zivadinov, a professor of neurology and director of the Buffalo Neuroimaging Analysis Center, said…

Gilenya (fingolimod) lowered relapse rates in children and adolescents with relapsing multiple sclerosis at a “magnitude” — almost 82 percent — never before seen in a scientific study and could be “life changing” for these hard-to-treat patients, a top researcher with Novartis, the treatment’s developer, said in an…

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…

MD1003, a high-dose biotin developed by MedDay, slowed or prevented further disease progression among progressive multiple sclerosis (MS) patients in a Phase 3 clinical trial, researchers announced at the Oct. 25–28 7th Joint ECTRIMS-ACTRIMS Meeting in Paris, France. The effects of the treatment were seen to be upheld over…

The 7th Joint ECTRIMS-ACTRIMS Meeting, taking place in Paris this month, is one of the largest scientific conferences focused solely on multiple sclerosis (MS), and the National Multiple Sclerosis Society will be among the many interested parties attending. To get a feeling for meeting highlights and presentations the…

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,…

Opioid growth factor (OGF) can serve as a new biomarker to determine diagnosis and progression of multiple sclerosis (MS), say researchers at Pennsylvania State University. Their study, “Serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone,” appeared in the journal Experimental Biology and…

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…

Specific gut bacteria may drive the progression of multiple sclerosis, according to a study showing that two bacterial species made the disease worse in a mouse model of MS. Researchers at the University of California, San Francisco also pinpointed a species — found in lower numbers in MS patients —…

Resistance training like weight lifting can protect or even regenerate the nerve cells of relapsing-remitting multiple sclerosis patients, slowing the progression of the disease, according to a clinical trial. A hallmark of MS is the brain shrinking faster than normal, and findings from this trial indicates that resistance training can slow the shrinking or even make some brain areas grow. Research has shown that physical training benefits MS patients, helping them alleviate many symptoms, including excessive fatigue and balance control problems. Recent studies suggest that exercise can have a disease-modifying role in MS. This means physical activity can be an important adjuvant, or add-on therapy, for standard-of-care regimens. Researchers followed 35 patients with relapsing-remitting MS for 24 weeks. Eighteen patients did resistance training twice a week, consisting of four lower- and two upper-body exercises. The other 17 patients struck with their normal routines. Before and after the 24 weeks, doctors took magnetic resonance imaging scans, or MRIs, to evaluate patients' brain structures. After the 24 weeks, the scans showed less brain shrinkage in those who had resistance training. Some of their cortical brain regions were also thicker — an indication they were growing. It is not clear why exercise benefits MS patients' brains, nor if exercise has the same effect on all patients. Additional studies are needed to clarify its therapeutic effect, the researchers said. That knowledge could help improve current MS therapies.

A new study draws a reverse link between the number of MRI scans of multiple sclerosis patients who are on interferon-beta 1a and doctors declaring there is evidence of the patients’ disease worsening. When doctors looked at one scan, rather than multiple ones, they were more likely to say that…

Costs associated with multiple sclerosis increase as the disease worsens, according to a study of more than 16,000 patients in 16 European countries. The study, “New insights into the burden and costs of multiple sclerosis in Europe,” was published in the Multiple Sclerosis Journal. Researchers obtained their information from patient self-reporting. Patients used the Kurtzke's Expanded Disability Status Scale (EDSS) to assess the severity of their disease. They also reported on their quality of life and their resource use. Patients were divided into three categories. Those with a score between 0 and 3 on the EDSS scale were deemed to have a mild disease. The disease of those with scores of 4 to 6.5 was considered moderate. And the disease of those with scores of 7 to 9 was classified as severe. Patients assessed their health-related quality of life with the EuroQol Five Dimensions questionnaire. The average age of the 16,808 participants was 51 and a half years old. The work capacity of MS patients dropped from 82 percent of a healthy person's to 8 percent as the severity of the disease increased, researchers said. Patients' quality of life scores were about the same as those seen in the general population when they had a mild disease. But they plunged to less than zero when their disease became severe. The mean annual cost of having a mild form of MS was 22,800 euros, or around $26,300, researchers reported. The cost of having a moderate disease was 37,100 euros, or about $42,800. And the cost of a severe disease was 57,500 euros, or $66,340. Healthcare accounted for 68 percent of total costs with a mild disease, 47 percent with a moderate disease, and 26 percent for a severe disease. "Costs are dependent on the availability, use and price of services and on disease severity," the researchers wrote. "Costs were related to disease severity" in all countries "and were dominated by production losses, non-healthcare costs and DMTs," or disease-modifying therapies. Those therapies may be a key reason why the highest percentage of healthcare costs occurred in patients with a mild disease, researchers said. Doctors prescribe a lot of DMTs to this group. Other factors related to the high percentage were that many patients with mild diseases are still able to work -- meaning they incur fewer production-loss costs -- and this group requires fewer community services. As MS becomes more severe, patients' production losses rise, and they use more community services. "The intensity of healthcare service use varied widely across the countries," researchers wrote. "This reflects differences in healthcare organization, medical traditions, ease of access and – most importantly – availability of given services." Researchers also assessed patients' levels of fatigue and cognitive difficulties. Ninety-five percent reported fatigue, and 71 percent cognitive difficulties. Fatigue and cognitive difficulties had significant impacts on quality of life scores, researchers said.