biomarkers

Blood Levels of IgG3 Antibodies May Predict Faster Shift to MS in Clinically Isolated Syndrome Patients, Study Says

Higher-than-usual levels of specific antibodies in the blood of patients with clinically isolated syndrome (CIS) may predict a faster progression to multiple sclerosis (MS), an Australian study reports. The specific antibody is known as IgG3, an immunoglobulin known to promote inflammation. The study, “Higher Serum Immunoglobulin G3 Levels May Predict…

#AAN2018 – Ocrevus Decreases Biomarkers of MS Patients’ Nerve Cell Damage, Phase 3 Trial Shows

Genentech’s Ocrevus (ocrelizumab) reduces levels of cerebrospinal fluid biomarkers that denote nerve cell damage in multiple sclerosis patients, a Phase 3 clinical trial shows. Researchers will present the results at the American Academy of Neurology’s annual meeting in Los Angeles, April 21-27. The presentation will be titled “Interim Analysis of the…

Low-dose Naltrexone Changes Levels of Inflammatory Proteins in MS, Study Shows

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.

Vitamin D Supplements Fail to Prevent Bone Loss in MS Patients, Study Reports

A new study reports that vitamin D supplements do not prevent bone loss in multiple sclerosis patients who are not vitamin-D-deficient. Previous research has suggested that low levels of vitamin D increase the risk of a person developing MS. In addition, Vitamin D prevents loss of bone density. That loss can lead to fractures and osteoporosis, a condition that many MS patients experience as their disease progresses. Researchers decided to investigate the effect of weekly doses of vitamin D3 on patients with relapsing-remitting multiple sclerosis, versus patients receiving a placebo. All 68 participants in the Phase 4 clinical trial also received 500 mg a day of calcium, a compound that is also important for bone health. The team measured the effectiveness of the supplemental vitamin D by analyzing biomarkers of bone health in blood. These included levels of the proteins PINP, or procollagen type I N propeptide, and CTX1, or C-terminal cross-linking telopeptide. At the start of the study, levels of PINP and CTX1 were not significantly different between the two groups. And that continued to be true at week 48 and week 96 of the study. The bottom line was that vitamin D supplementation did not change bone health in patients with MS after 96 weeks. “Our results do not support that high dose weekly vitamin D supplementation is beneficial for bone health in ambulatory persons with MS, and suggest that weekly vitamin D supplementation alone is not sufficient to prevent bone loss in persons with MS who are not vitamin D deficient,” the researchers concluded. The results were different from previous studies supporting the beneficial effects of vitamin D supplementation in MS patients. The researchers said they believed the discrepancy was due to differences in the studies' patient characteristics, sample size, and duration of follow-up.

Progressive MS Alliance Awards $18M to 3 Research Projects into Disease Treatments, Expanded Testing

The International Progressive Multiple Sclerosis (MS) Alliance, a worldwide group of MS organizations that support research efforts, has awarded three, four-year grants — called Collaborative Network Awards, and worth $6 million each — to speed work into potential treatments for progressive MS. Found in about 15 percent of all initially diagnosed…

Blood Biomarkers of Multiple Sclerosis May Predict a Person’s Response to Treatment

Blood biomarkers in individual multiple sclerosis patients may help clinicians determine which treatments would be of most benefit to that person, according to researchers at Oklahoma Medical Research Foundation (OMRF). The study, published in the journal Neurology, Neuroimmunology & Neuroinflammation, is titled “Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients.”…

NIH Study into Progressive MS Biomarkers to Be Presented at ACTRIMS 2016

Scientists from the Neuroimmunological Diseases Unit at the National Institutes of Health (NIH) will present results of a study investigating several biomarkers that might lead to a more sensitive and accurate diagnostic test of central nervous system (CNS) inflammation, a key aspect of progressive multiple sclerosis (MS). The data is being reported today, Feb.18, at the…

MS Patients’ Likely Response to Interferon-β May Be Evident in a Blood Biomarker

A new study underscores the variability of immune responses in different people with multiple sclerosis (MS) and suggests this heterogenity affects responses to the commonly prescribed MS medication interferon-β, but blood biomarkers may exist that can help to determine those most likely to benefit from such treatment. The study, “Cytokine profiles…

Potential MS Therapeutic Targets Found in Plasma Metabolites

In a new study entitled “Untargeted plasma metabolomics identifies endogenous metabolite with drug-like properties in chronic animal model of multiple sclerosis,” a team of researchers performed a comparative analysis of metabolites between control mice and a mouse model with experimental autoimmune encephalitis (EAE, the most commonly used…

Biomarkers and Predictors For Developing Future Personalized MS Therapies Discussed at ECTRIMS 2015

New developments in the diagnosis and treatment of multiple sclerosis (MS) are being discussed at this year’s 31st annual Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The symposium, being held in Barcelona, Spain, will foster discussions about development of individualized therapies for MS patients through a more targeted and efficient…

LMU Researchers Identify Biomarker BCMA to Measure MS Severity

In a recent study published in the journal Nature Communications, LMU clinicians have clarified the lifespan of antibody-producing cells and have also identified a novel biomarker that could be used to monitor autoimmune conditions such as multiple sclerosis and lupus erythematous. The humoral immune response is mediated by cells…

Amarantus Releases Preliminary Data From Blood-Based MS Diagnostic

Amarantus BioScience has released preliminary data from a blood test for multiple sclerosis (MS) called the MSPrecise diagnostic. The company believes that the test could lead to more accurate diagnoses of MS early in the disease’s progression. MSPrecise is a DNA sequencing test designed to identify specific DNA mutations that are associated with the…