August 6, 2018 News by Jose Marques Lopes, PhD Loss of Specific microRNA Seen to Lessen Disease Severity and Myelin Loss in MS Mouse Model Removing a specific microRNA molecule ā miR-150 ā eased disease severity, inflammation, and loss of myelin in a mouse model of multiple sclerosis (MS), researchers report. Their study, āSilencing miR-150 Ameliorates Experimental Autoimmune Encephalomyelitis,ā was published in the journal Frontiers in Neuroscience. Micro RNAs (miRNAs) are…
August 3, 2018 News by Marta Figueiredo, PhD 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 syndromeĀ (CIS) may predict a faster progression toĀ multiple sclerosisĀ (MS), an Australian study reports.Ā The specific antibody is known as IgG3, anĀ immunoglobulin known to promote inflammation. The study, āHigher Serum Immunoglobulin G3 Levels May Predict…
August 2, 2018 News by Alice MelĆ£o, MSc Potential B-cell Targeting Oral MS Treatment, PRN2246, Shows Ability to Reach Brain in Phase 1 Study Results from a first-in-human study assessing the safety and early activity of PRN2246Ā confirmed that the oral compound can reach into the brain and spinal cord. This finding adds new evidence that PRN2246 has the potential to target the immune cells that drive the inflammatory process involved in multiple sclerosis…
June 19, 2018 News by Patricia Inacio, PhD Atara Biotherapeutics Study Links Epstein-Barr Virus Infection with MS Analysis of post-mortem brain samples from multiple sclerosis (MS) patients and healthy individuals (without neurologic disease) showed that while signs of Epstein-Barr virus (EBV) infection are present in both groups of brains, EBV-positive immune cells were more prevalent and densely populated in the MS brain. The study reporting those findings,…
June 5, 2018 News by Patricia Inacio, PhD #CMSC2018 – New Phase 2 Data Supports Ublituximab in Effectively Lowering Relapses, Depleting B-cells in MS Patients New results from a Phase 2 trial evaluating TG Therapeuticsā ublituximab continue to support the therapy’s efficacy in treating relapsing forms of multiple sclerosis (MS). This investigative infusion therapy is now moving into a Phase 3 study. Treatment with 450 mg of ublituximab delivered intravenously in a rapid fashion…
May 14, 2018 News by Jose Marques Lopes, PhD B-Cell Changes May Predict Conversion from Clinically Isolated Syndrome to MS, Study Suggests B-cell alterations in peripheral blood may predict the conversion of clinically isolated syndrome (CIS) to multiple sclerosis (MS), a recent study suggests. Conducted in Turkey, the study, āPeripheral blood memory B cell frequency predicts conversion from clinically isolated syndrome to multiple sclerosis,ā was published in…
May 14, 2018 News by Patricia Inacio, PhD Biomarker in Cerebrospinal Fluid Seen to Predict MS Progression in Study A potentialĀ biomarker ā the ratio of antibody proteins in cerebrospinal fluid at the time of diagnosis ā was seen to predict which Ā multiple sclerosis patients will progress into full-blow disability some five years after being diagnosed in a new study. If confirmed in larger clinical studies, this biomarker could to…
May 1, 2018 News by Patricia Inacio, PhD #AAN2018 ā Ocrevus Lowers Immune Response to Vaccines in Relapsing MS, Phase 3 Trial Shows Treatment with Ocrevus (ocrelizumab)Ā is linked to a reduced immune response to vaccinations inĀ patients with relapsingĀ multiple sclerosis (MS), according to a Phase 3 trial. These results were recently presented at the 2018 American Academy of Neurology (AAN) Annual MeetingĀ in Los Angeles in a presentation titled, āEffect of Ocrelizumab on Vaccine Responses in Patients With Multiple Sclerosis.ā GenentechāsĀ Ocrevus is an approved MS therapy that targets the CD20 protein located on the surface of B-cells, targeting the cells for destruction. B-cells are immune system cells involved, for example, in the production of antibodies necessary to fight off infection. At the AAN meeting, researchers reported that in MS patients,Ā treatment with Ocrevus decreased the ability of B-cells to activate other immune cells, improving the rate of MS attacks. Penn Medicine neurologist Amit Bar-Or, MD, presented these findings, which showed that interactions between different classes of immune cells, such as B- and T-cells, promote MS attacks. Vaccination against infections is an important part of the management of patients with MS. So, in a second study (NCT02545868), researchers investigated the impact treatment with Ocrevus has on patient response to vaccines. They recruited 102 patients with relapsing MS and randomized them in two groups. In group A, 68 people received a single dose of 600 mg Ocrevus (administered into the blood); in group B, 34 patients received no disease-modifying therapy or interferon-beta. All patients were then administered vaccines for tetanus, seasonal flu, and pneumococcus.Ā Patients in group A received the vaccines 12 weeks after they were treated with Ocrevus, while group B patients received the vaccines on day one. Researchers also tested patientsā response to a novel protein (an antigen) never "seen" by their immune system, called keyhole limpet hemocyanin (KLH) neoantigen. The vaccinations led to an immune system response in all patients, but the level of response in patients treated with Ocrevus was lower. A positive response to the tetanus vaccine at eight weeks after treatment was 23.9% in group A (Ocrevus) compared with 54.5% in group B (no treatment); the response to pneumococcus vaccination was 71.6% in group A and 100% in group B. After four weeks of treatment, the levels of antibodies against the different strains of the flu virus were lower in Ocrevus-treated patients than in the control group, ranging from 55.6% to 80.0% in the Ocrevus group compared with 75.0% to 97.0%Ā in the controls. The immune response to the neoantigen KLH was also decreased in the Ocrevus group. "This study shows that while people with MS treated with ocrelizumab [Ocrevus] can still mount vaccine responses, it's not nearly as strong as prior to treatment," Bar-Or said in a press release. "While antibody responses were reduced in the ocrelizumab treated patients, they still responded to a certain level," he said. "This is valuable information in terms of seasonal vaccines such as the flu ā it appears safe for patients taking ocrelizumab to get vaccinated and vaccination is likely to provide them with at least some protection from such infections." These findings correlate with standard guidelines that advise patients to undergo vaccinations six weeks before they start treatment with Ocrevus.
April 26, 2018 News by Patricia Inacio, PhD #AAN2018 – CladribineĀ Injections Deplete Number of Memory B-cells in RRMS, Study Shows CladribineĀ treatment leads to a selective depletion of memory B-cells in patients with relapsing-remittingĀ multiple sclerosisĀ (RRMS), researchers report. The results are in the presentation āCladribine for the Effective Control of Multiple Sclerosis via Memory B Cell Depletionā being given Friday, the final day of the 2018 Annual MeetingĀ of theĀ …
April 18, 2018 News by Patricia Inacio, PhD #AAN2018 – Ocrevus Decreases Biomarkers of MS Patients’ Nerve Cell Damage, Phase 3 Trial Shows Genentech’sĀ Ocrevus (ocrelizumab)Ā 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 theĀ American Academy of Neurology’s annual meetingĀ in Los Angeles, April 21-27. The presentation will be titled āInterim Analysis of the…
February 26, 2018 News by Alice MelĆ£o, MSc Oxygen Sensor Protein Can Regulate B-Cell Anti-inflammatory Response in MS, Study Shows Oxygen sensor proteins can regulate immune B-cell activity, preventing inflammation in autoimmune disorders such as multiple sclerosis, a study reports. The research, titled āHypoxia-inducible factor-1Ī± is a critical transcription factor for IL-10-producing B cells in autoimmune disease,ā was published inĀ Nature Communications.Ā An autoimmune disease is one in…
January 16, 2018 News by Patricia Inacio, PhD Long-term Rituxan Treatment Is Effective and Safe in MS, Study Shows The approved lymphoma therapy Rituxan (rituximab) has shown promise as a treatment for Ā multiple sclerosis. A new study indicates the Genentech treatment is effective and safe against neurological diseases like MS for up to seven years. The research, āLong-term safety of rituximab induced peripheral B-cell depletion in…
November 13, 2017 News by Patricia Silva, PhD Sanofi and Principia Join to Develop Potential B-Cell-targeting Oral MS Treatment Sanofi Genzyme and Principia BiopharmaĀ have entered into a license agreement to advance the clinical development of PRN2246, an oral drug candidate for the treatment of multiple sclerosis and other diseases of the central nervous system. PRN2246 is an inhibitor of the Brutonās tyrosine kinase, an enzyme encoded by the BTK gene that plays a crucial role in B-cell development and the B-cell signaling pathway. B-cells are known to be involved in the development of autoimmune diseases that affect the nervous system, including multiple sclerosis. PRN2246 is an orally available therapy designed to easily access the central nervous system (brain and spinal cord) by crossing the blood-brain barrier, and impact the signaling of immune cells and brain cells involved in autoimmunity and inflammatory processes. The drug is designed to safely and effectively modulate B-cell function without depleting these cells. A Phase 1 clinical trial is now testing the drug's safety in healthy volunteers. Under the agreement, which is expected to close shortly, Principia will grant Sanofi an exclusive, worldwide license to develop and commercialize PRN2246. Principia, in return, will receive $40 million in upfront payments from Sanofi, and future milestone payments could reach $765 million. Principia will retain the option to co-fund the treatment's Phase 3 development in exchange for other royalties in the United States. Principia has developed a novel way toĀ design and develop better and safer therapies based on oral small molecules. The company uses its proprietaryĀ Tailored Covalency technologyĀ to develop its drug candidates, which are, according to the company's website, safer, and more selective, potent and durable than other available treatments. The terms of this licensing agreement are still subject to customary regulatory approval.
November 6, 2017 Columns by Ed Tobias MS News That Caught My Eye Last Week: Older Patients, Stem Cells, Myelin, B-cells vs. T-cells #MSParis2017 ā Trial to See if Disease-modifying Therapies Not Necessary in Older MS Patients This tops my list this week because, at age 69, I certainly fit the definition of an “older” MS patient. The study is hoping to enroll 300 MS patients in the U.S. who…
October 31, 2017 News by Patricia Silva, PhD #MSParis2017 – T-cell vs. B-cell Debate More Meeting of Minds Than ‘Rumble in the Jungle’ News commentary One particular session on Day 2 of the four-day 7th Joint ECTRIMS-ACTRIMS Meeting ā which drew 10,000 researchers, doctors, industry representatives, and patient advocates to hear about advances in multiple sclerosis (MS) treatment and understanding ā attracted so much interest that all seats were taken in the…
October 24, 2017 News by Alice MelĆ£o, MSc Two Studies Show IL-35 Protein’s Potential to Curb Inflammation in Autoimmune Diseases An immune signaling protein called interleukin-35 has anti-inflammatory properties that scientists might harness to develop a therapy for multiple sclerosis and other autoimmune disorders, according to two studies. Researchers at the National Eye Institute of the National Institutes of HealthĀ discovered that a subunit of interleukin 35, which is also known as IL-35, significantly reduced inflammation in mouse models of eye inflammation and multiple sclerosis. Immune B-cells produce IL-35 to communicate with, and regulate the behavior of, surrounding cells. In aĀ previous study, the research team found that the protein could inhibit inflammation in the eyes of animals with autoimmune uveitis, or inflammation of the inner layers of the eye. An autoimmune disease is one in which the immune system attacks healthy cells instead of invaders. A drawback of trying to use a synthetic version of IL-35 as a therapy is that it's difficult to produce because of its complex structure and it's unstable in a solution. Natural IL-35 is composed of two subunits, IL-12p35 and Ebi3, which bind to create the full protein. The team wondered if they could use a subunit, instead of the full protein, as an anti-inflammatory agent. Their study,Ā āIL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease,ā was published in the journal Nature Communications, They demonstrated that the IL-12p35 subunit could generate anti-inflammatory effects similar to those of the full IL-35 protein. Giving IL-12p35 to mice with uveitis promoted the expansion of immune B-cells that counteract autoimmune responses, reversing the animals' eye symptoms. In the second study, researchers discovered that the subunit tempered inflammation in a mouse model of multiple sclerosis. Giving the animals IL-12p35 every other day for up to 12 days promoted immune cell proliferation that inhibited inflammation in the mice's brains and spinal cords, improving their symptoms. The research demonstrated IL-35 and its subunit's potential to treat nerve-inflammation disorders.Ā The team published its findings in the journal Frontiers of Immunology. The article is titled āIL-12p35 inhibits neuroinflammation and ameliorates autoimmune encephalomyelitis.ā The team is now looking at IL-12p35's ability to treat other degenerative eye diseases, such as diabetic retinopathy and macular degeneration.
October 19, 2017 News by Patricia Silva, PhD #MSParis2017 – TG Therapeuticsā Ublituximab Depletes Harmful B-cells and Lowers MRI Lesions, Trial Shows TG TherapeuticsāĀ ublituximab nearly eradicated a type of immune B-cell believed to be involved in multiple sclerosis,Ā according to a Phase 2 clinical trial. The result was that none of the patients had a relapse during the first six months of the trial, which is continuing, researchers said. In addition,Ā ublituximabĀ reduced the brain and spinal cord lesions of the relapsing MS patients involved in the trial and prevented new ones from forming. The company will present the interim trial results in threeĀ poster presentations at theĀ 7th Joint ECTRIMS-ACTRIMS Meeting in Paris, Oct. 25-28. Meanwhile, researchers will continue to study the effectiveness of ublituximab, a B-cell-depleting antibody, versus a placebo, for another six months. The trial is being held at several U.S. medical facilities. Participants receive two initial infusions of ublituximab or a placebo on day 1 and 15 during the first 28 days. After this initial period, those in the placebo-group are also given ublituximab and followed for 52 weeks. A key trial finding was thatĀ over the initial 24 weeks of the trial, the treatment nearly wiped out a type of B-cell known as CD20 that scientists believe is involved in the development of MS. Only 1 percent of the B-cells remained after a month. While helpful immune T-cell numbers dropped slightly after the first ublituximab infusion, they bounced back quickly. Researchers also reported a reduction in patients' magnetic resonance imaging (MRI) lesions, with no new inflammatory lesions appearing during the six months. So far, none of the trial participants has had a serious adverse event. Most of the adverse events were mild or moderate and related to the infusions. The trial also demonstrated that speeding up infusions did not increase infusion-related reactions.Ā The speed-up results indicated thatĀ ā if proven effective and safe ā ublituximab will be more convenient for patients than B-cell-depleting drugs that require infusions stretching over several hours.
October 10, 2017 News by Patricia Silva, PhD Researchers Identify Quality Control Regulatory Cells That Prevent the Production of Autoantibodies The discovery of an immune cell quality control mission may have put scientists a step closer to understanding how autoimmune conditions such as multiple sclerosis arise. University of Alabama at BirminghamĀ researchers identified regulatory immune cells with the quality control mission of destroying antibody-producing B-cells that mistakenly target the body's own tissue after an infection. An autoimmune disease is one in which the immune system attacks healthy tissue or organs instead of invaders. Eventually, the insight could lead researchers to new approaches for treating MS and other conditions caused by aberrant immune reactions. The Alabama researchers were studying the processes involved in the body's defense against a real threat āĀ the influenza virus āĀ when they discovered a population of immune cells whose action is relevant to autoimmune diseases. The study noted thatĀ T follicular regulatory cells appeared in the late stages of influenza infection. Their objective was to prevent the immune system from generating self-reactive antibodies ā that is, those that attack the body's own tissue. These cells are poorly understood, the researchers explained. Their experiments, published in the journal Nature Immunology, focused onĀ the molecular events surrounding the cellsā actions.Ā The teamĀ discovered that about a week after the infection, levels of an immune regulator called the IL-2 protein increased. This triggered the multiplication of common regulatory T-cells, or Tregs. When this phase of the immune reaction was fading, TFR cells started multiplying, reaching peak numbers about a month after infection. The formation of the TFR cells was therefore tightly linked to the processes controlling Treg production, researchers said, with falling levels of IL-2 allowing the new phase of the immune response. The TFR cells migrated to the lymph nodes āĀ the headquarters of antibody-producing B-cells. Here, B-cells proliferate and change their antibody-producing genes to create new, stronger antibodies. But sometimes the gene changes, or mutations, give rise to an antibody that attacks the body, instead of invaders. Researchers discovered that TFR cells prevented B-cells, which gave rise to autoantibodies, from accumulating in the lymph nodes. Importantly, the TFR cells had no impact on the immune processes targeting the influenza virus. When researchers prevented TFR cells from forming or removed them from mice, the animals started producing autoantibodies, they explained. While this suggested that people with autoimmune diseases may have flawed TFR processes, the study did not investigate this, making the topic a possibility for future studies.
August 22, 2017 News by Patricia Inacio, PhD Autoimmunity Traced to Failure of B-cell Protein, Caveolin-1, to Work as Intended in Study A newĀ and potentially important mechanism in the development ofĀ autoimmune diseases likeĀ multiple sclerosis was discovered by scientists at the University of Freiburg, Germany. They identify aĀ protein, called Caveolin-1, that is essential to immune cells called B-cells working as intended to protect a person from pathogens or ā in its absence…
July 10, 2017 News by Patricia Silva, PhD B-cell-secreted Toxins Kill Neurons and Myelin-Producing Cells, MS Study Reports B-cells of patients with relapsing-remitting multiple sclerosis (RRMS) secrete substances that are toxic to both neurons and neuron-protecting myelin-forming cells, causing both kinds to die, according to a study. Despite analyses of numerous inflammatory and other factors believed to drive MS processes, researchers were unable to identify the molecules that are toxic, however. Dr. Robert Lisak of Wayne State University in Detroit, Dr. Amit Bar-Or of McGill University in Montreal and their teams are now working on identifying the factor, and learning if the process is also involved in progressive MS. Their study, āB-cells from patients with multiple sclerosis induce cell death via apoptosis in neurons in vitro,ā was published in the Journal of Neuroimmunology. It demonstrated that B-cells gathered from the blood of RRMS patients killed lab-grown neurons and oligodendrocyte cells, which form myelin, a protecting coating for nerve cells. Deterioration of the myelin coating and the death of neurons are hallmarks of MS. An earlier study the team conducted indicated that B-cells from MS patients could kill oligodendrocytes. But since the experiments involved only three patients and three controls, the team scaled up their experiments to include 13 patients and an equal number of controls. Both rat and human neurons died when mixed with MS-derived B-cells. In contrast, B-cells from healthy people had little or no impact on the survival of the brain cells. Researchers also discovered that the secreted toxic molecules had no impact on other types of central nervous system cells ā astrocytes and microglia. The toxins killed only neurons and myelin-producing cells. The B-cells triggered a process called apoptosis, or programmed cell death, researchers said. This is basically a suicide program. It tells a cell to die when exposed to stressful factors or toxins. The process differs from cell disintegration. Despite thoroughly screening about 40 inflammation-related substances, researchers were unable to identify any factors that caused the cells to die. The National MS Society and the Research Foundation of the MS Society of Canada funded the research, which the U.S. society highlighted in a news release. In the newest phase of the study, researchers will try to learn more about the processes underlying neuron and myelin-related cell deaths and identify the factors responsible. In addition to testing B-cells from progressive MS patients, the team will examine patients with other autoimmune conditions to see if the process is unique to MS or not. Researchers increasingly realize that B-cells are important to MS processes. This observation was underscored by U.S. regulators' approval of the B-cell depleting therapy Ocrevus (ocrelizumab) at treatment for both relapsing and primary progressive MS.
July 7, 2017 News by Patricia Silva, PhD Mavenclad Reduces MS Relapses by Resetting the Immune System New analyses of how Merckās Mavenclad (cladribine tablets) act to treat relapsing multiple sclerosis (MS) give researchers an entirely new picture of immune processes leading to the disease. Data showed that the drug lowers both immune B-cells and, to a lesser degree, T-cells. But the numbers of both cell…
June 28, 2017 News by Patricia Silva, PhD In Ongoing Phase 2 Trial, Ublituximab Seen to Effectively and Safely Deplete B-cells TG Therapeutics’ investigational treatment āĀ ublituximab (TG-1101)Ā ā led toĀ a near total depletion of B-cells in patients with relapsing forms of multiple sclerosis (MS) taking part inĀ an ongoing Phase 2 trial, the company recently announced. In addition, the company said that ublituximabĀ hadĀ anĀ infusion time as short as one hour,Ā without excessive side…
June 22, 2017 News by Alice MelĆ£o, MSc MS Researcher Stephen Hauser, MD, Awarded the 2017 Taubman Prize Stephen L. Hauser, MD, director of theĀ University of California, San Francisco (UCSF)‘s Weill Institute for Neurosciences,Ā has been awarded the 2017 Taubman Prize for Excellence in Translational Medical Research. Recognized for scientific work that challenged the way multiple sclerosis (MS) is regarded, Hauserās discoveries have opened new therapeutic…
June 13, 2017 News by Patricia Silva, PhD Unpublished Data May Point to Link Between Lemtrada and Other Autoimmune Diseases in MS Patients Previously unpublished results of clinical trials of Lemtrada (alemtuzumab) appears to contain key information as toĀ why many multiple sclerosis patients who use it develop other autoimmune diseases. Researchers looked at the immune cell mix after Lemtrada depleted many of those cells. They discovered that certain B-cells repopulate the body earlier…
June 7, 2017 News by Patricia Silva, PhD Ocrevus Phase 3 Trial Will Explore How Treatment Works by Viewing Changes in Spinal Fluid Already an approved treatment for relapsing and primary progressive multiple sclerosis (MS), Ocrevus (ocrelizumab) is still undergoingĀ scrutiny in several clinical trials. MostĀ focus on the drugās effects in specific patient groups, but one studyĀ aims to advanceĀ understanding ofĀ how Ocrevus works to harness disease. To do so, the open-label Phase 3…
April 24, 2017 News by Patricia Silva, PhD ATA188, Which Kills B-Cells Targeting Epstein-Barr Virus, Shows Promise as MS Treatment An investigational treatmentĀ called ATA188 that wipes out B-cells targeting the Epstein-Barr virus (EBV) has shown promise as a multiple sclerosis treatment, a Phase 1 clinical trial involving a small patient group indicates. The trial, conducted in Australia, covered six people with primary or secondary progressive MS. B-cells are a…
April 5, 2017 News by Joana Fernandes, PhD UCSF Neurologist Played Key Role in MS Research Turning to B-Cells, Essential Step to Ocrevus Dr. Stephen Hauser, chair of the neurology department at the University of California San Francisco, was instrumental in the early research and laterĀ clinical trials that ultimately led toĀ Ocrevus (ocrelizumab), the first therapyĀ approved by the U.S. Food and Drug Administration (FDA)Ā for bothĀ relapsing MSĀ (RMS) and primary progressive multiple sclerosis…
April 3, 2017 News by Patricia Silva, PhD What Every MS Patient Should Know About Ocrevus and Its Use With the recent approval of Ocrevus (ocrelizumab) for both primary progressive and relapsing multiple sclerosis (MS), interest in the medication is peaking.Ā To helpĀ readers of Multiple Sclerosis News TodayĀ better understandĀ this new medication and how it works, as well issues dealingĀ with access, use, and potential side effects, here is aĀ summary…
March 28, 2017 News by Patricia Silva, PhD FDA Approves Ocrevus as 1st MS Treatment for Both Relapsing and Primary Progressive Forms At long last, and for the first time in medical history, peopleĀ with both relapsing and primary progressive forms of multiple sclerosis have reason to celebrate. The U.S. Food and Drug Administration (FDA) today approved Ocrevus (ocrelizumab)Ā as a disease-modifying therapy for both forms of MS, aĀ chronic autoimmune disease.
March 28, 2017 News by Patricia Silva, PhD Ocrevus’ Journey from Defiant Idea to Game-Changing Treatment Twenty years ago, the idea that B-cell depletion could treat multiple sclerosisĀ would have been greeted with a hearty laughĀ byĀ any well-respected neurologist or MS researcher ā or perhapsĀ a scoff. But times change and research advances. Today, a medicine that gets rid of certain B-cells may beĀ the most powerful drug yetĀ developed against…