disease progression

Levels of a protein stemming from brain cell damage can mirror the severity and symptoms of multiple sclerosis, an analysis of combined data from three trials showed. Researchers will present this and related findings at the annual meeting of the American Academy of Neurology in Los Angeles, April 21-27. The…

Today is Walk MS, and for the first time since my diagnosis, I am not there. While I am not one to feel sorry for myself, this stings. I miss being among the sea of impassioned orange warriors. I miss the tears that fall as cheers accompany me through…

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.

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.

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…

Sanofi Genzyme‘s Lemtrada (alemtuzumab) and Biogen’s Tysabri (natalizumab) are more effective in preventing conversion to secondary progressive multiple sclerosis (SPMS) compared to older injectable drugs, researchers from the University of Cambridge in the U.K. reported at the 7th Joint ECTRIMS-ACTRIMS Meeting Oct. 25-28 in Paris. The…

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 —…

MSBase and icometrix have joined efforts in a large-scale project to identify imaging markers of multiple sclerosis (MS) that could help diagnose the disease in its early stages. The combination of magnetic resonance imaging (MRI) information collected from MS patients with clinical information from the MSBase Registry can offer new insights in disease progression, potentially leading to new predictive tools for MS. It may also promote more standardized use of imaging measures in clinical practice. With more than 52,000 MS patients, the MSBase Registry is an international database committed to collecting patients’ information as well as sharing, tracking and evaluating overall outcome data in MS and other neurological conditions. Until now, the MSBase Registry included only descriptive information regarding patients' imaging analysis results, with no access to full imaging data. This joint, large-scale project will include MRI scan data routinely acquired in clinical setting taking advantage of icometrix’s software platform, MSmetrix. “We wish to unlock the power of MRI for personalized monitoring in MS," Helmut Butzkueven, director of MSBase, said in a press release. "The MSBase Scientific Leadership group has selected MRI integration as the top strategic priority for MSBase. We believe that already conducted MRI scans represent an enormous missed opportunity, because advanced measurements to assess change over time from these scans are not currently in practical use.” Butzkueven said MSBase "will test the predictive power of this unlocking of MRI data in the first phase," with a total of 10,000 MRI data points in at least 3,000 MS patients from all over the world. The project is expected to identify disease progression markers that could help detect early signs of MS by MRI evaluation. This investigator-initiated collaboration between icometrix and the MSBase Foundation is being supported by three global pharmaceutical giants: Novartis, Biogen and Roche. “MRI measures play an essential part in the complex puzzle of MS,” said Danny Bar Zohar, global head of neuroscience development at Novartis. “Partnering with MS Base and icometrix in this exciting project will bring the acquisition of high-quality real world data to the next level, ultimately improving the outcome of people living with MS.”

Fatigue and limited leg function are more common among older people with progressive multiple sclerosis than in those with relapsing forms of the disease, according to a study. In fact, they are a sign that the disease of a person with relapsing MS is becoming worse by reaching the progressive MS…

Laquinimod failed to meet its primary Phase 3 clinical trial objective of slowing the progression of relapsing-remitting multiple sclerosis (RRMS) after three months, according to its developers, Teva Pharmaceutical Industries and Active Biotech. That has prompted the partners to abandon their quest to use the therapy to treat RRMS. Laquinimod…

An extension of a Phase 3 clinical trial has shown that early treatment with Rebif (interferon beta-1a) in patients with initial manifestations of multiple sclerosis (MS) can prolong the time to a clinically definite multiple sclerosis (CDMS) diagnosis over five years. The study, “Subcutaneous interferon β-1a in…

Stem cell transplants are most effective if done in young multiple sclerosis (MS) patients in early disease stages, who have not gone through several rounds of other treatments, according to a large study that followed transplant patients for more than five years. Study results also found that people with relapsing MS are much…

Gilenya (fingolimod) a multiple sclerosis (MS) drug developed to target the immune system and control inflammation, can also reduce the negative action of astrocytes, further controlling inflammation, says a new study. The article, “Sphingosine 1-Phosphate Receptor Modulation Suppresses Pathogenic Astrocyte Activation and Chronic Progressive CNS Inflammation,” appeared in the…

EMD Soreno has recently published Phase 3 clinical data showing that Cladribine tablets reduced the annualized rate of brain volume loss (BVL, brain atrophy) compared to placebo in patients with relapsing-remitting multiple sclerosis (RRMS). The study, “Reduced brain atrophy rates are associated with lower risk of disability progression…

Scientists have discovered the first blood biomarker for multiple sclerosis (MS) –  a chemical identifier in the blood. The discovery should lead to a simple blood test that makes it quicker and easier to follow the course of MS, a debilitating disease of the central nervous system affecting around 2.3 million people…

A newly concluded clinical trial gives scientific evidence of the benefits that a stem cell transplant holds for multiple sclerosis (MS) patients who fail to respond to medications — with researchers calling the procedure a reasonable option for those with high disease activity. Five years after the treatment — high-dose immunosuppressive therapy followed by autologous hematopoietic cell transplant — further disease…

Many multiple sclerosis (MS) patients have a reduced sense of smell, and the more relapses they have, the worse the problem, according to a study suggesting that smell may be a marker for the disease’s progression. Findings also suggested a connection between reduced sense of taste and MS progression. The…

MicroRNAs in the blood could serve as biomarkers to monitor the progression of multiple sclerosis (MS), as well as help identify which mechanisms are at play in each patient, such as inflammation and tissue damage, according to new research. The findings were reported in the study, “Association Between Serum…

Cyclophosphamide (CPM) may delay the progression of disability in the first years of secondary progressive multiple sclerosis (SPMS), but patients must take it for two years — and many are unlikely to tolerate it for that long. The study, “Double-Blind Controlled Randomized Trial of Cyclophosphamide versus Methylprednisolone in Secondary Progressive…

People with late-onset multiple sclerosis (MS) tend to more rapidly rise in disability scores than younger patients with early onset MS, according to study in MS patients in Kuwait that compared their scores during follow-up consultations. Typically, the first symptoms of  multiple sclerosis occur between the ages of 18 and 40, with…

The presence of certain brain and spinal cord lesions can be used to predict if an MS patient with clinically isolated syndrome will progress into relapsing or secondary progressive multiple sclerosis (SPMS) within 15 years. Researchers agree that knowing which patients who will rapidly deteriorate will help physicians tailor both…

The 37th annual congress of The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) will take place in London between 14 – 17 September 2016.

Patients with aggressive onset multiple sclerosis, characterized by a rapidly progressing disease course and accumulation of disability, may benefit from early aggressive therapies instead of the escalation approach commonly given multiple sclerosis (MS) patients, according to researchers at Weill-Cornell Medical College. Their article, titled “A study of patients with…

RedHill Biopharma announced that the final patient has completed the last step of its Phase 2 clinical study (CEASE-MS) of RHB-104 as a potential treatment for people with relapsing-remitting multiple sclerosis (RRMS). RHB-104 is an antibiotic oral medication that blocks inflammation in addition to killing bacteria. RHB-104 was originally developed as a treatment for…

Opinions voiced by multiple sclerosis (MS) patients as to what they most want from, and like in, an MS treatment differ widely, although delaying progression and relapses — and minimizing serious side effects — clearly score high, according to new research from the University of British Columbia in Canada. The study, “Quantitative…

High blood pressure may be linked to greater overall disability in people with multiple sclerosis (MS), although the rate at which disability progresses might be slower than in patients without hypertension, a retrospective study concludes. The research, involving a large number of MS patients, helps to clarify a rather confusing range of views on how…

The complement system, a part of our non-adaptable (innate) immune defenses, is activated in lesions inside the brain’s gray matter and may well contribute to the relentless progression of multiple sclerosis (MS), researchers report. The findings offer new insights into mechanisms driving the development of this disease — particularly its primary progressive forms.

A retrospective study of vitamin D status and disability progression in multiple sclerosis patients — using real-life, clinical data from a large and varied group — found no  correlation between the two, although vitamin D levels may predict the occurrence of relapses in some patients. But these findings may have been limited by the lower doses of daily vitamin…

Researchers at the University of Technology Sydney (UTS) ithree institute are taking a novel approach in an attempt to halt disease progression in multiple sclerosis (MS). The scientists are planning to explore the anti-inflammatory potential of a controlled infection by parasitic worms as a way of preventing the harmful over-inflammation observed in MS and…

Sanofi Genzyme announced that it entered into a research collaboration with the Johns Hopkins School of Medicine to better understand the underlying causes of disease progression in multiple sclerosis (MS). Sanofi Genzyme has a number of research partnerships with MS academic medical centers, focused on exploring the pathogenesis of MS and potential new…