The loss of immune B-cells, and the resulting changes in the profile of immune T-cells, is a major mechanism of action for the beneficial effects seen with ublituximab treatment in multiple sclerosis (MS) patients, a study suggests. B-cells are a type of immune cell best known for producing…
treatment
Treatment with Sanofi Genzyme’s Lemtrada (alemtuzumab) for up to two years lowers the levels of serum neurofilament light chain (sNfL), a proposed biomarker of nerve damage, in relapsing-remitting multiple sclerosis (RRMS) patients to levels comparable to those seen in healthy people, data from the CARE-MS I study shows. Lemtrada’s effectiveness…
More than 15 disease-modifying therapies (DMTs) are available in most high-income countries to treat multiple sclerosis (MS). DMTs come in the form of injectables, infusions, and pills. Some are new, others have been around for more than 20 years. Some have a greater possibility of serious side effects than others. Some DMTs are highly effective at slowing or stopping disease progression; others, not so much. It's a difficult choice to make. So, why are some neurologists making it harder? These doctors are handing their patients a medication "shopping list" and telling them to pick one. I see this topic discussed regularly in social media MS groups. Recently, a woman who needs to switch DMTs wrote that her neuro gave her a "handful of (medication) brochures" and told her to go home and decide which medication she wanted. Really? DMT selection shouldn't be do-it-yourself I've been using DMTs for more than 20 years. I've been on Avonex (interferon beta-1a), Tysabri (natalizumab), Aubagio (teriflunomide), and Lemtrada (alemtuzumab). I always had the final say on which med I wanted to use, but I never had to make that decision alone without guidance from my neuro. That's the way a doctor-patient relationship should work. While the final DMT decision should always rest with the patient, your neurologist has the responsibility to use his or her knowledge of the meds and of you to guide you in your choice. Some factors that you both need to consider are: Is the disease progressing quickly or slowly? Your lifestyle: Do you work full time? Do you have a good support system and reliable transportation? If an injectable DMT is in the mix, can you handle injecting yourself monthly, three times a week, or every day? How much possible risk are you willing to accept in exchange for the potential of a better result? An additional and criticial consideration is whether you can afford the treatment. My impression is that cost is rarely thought of or talked about before most physicians prescribe a medication. I see nothing wrong with asking your doctor how much you can expect to pay out-of-pocket. (Or, for the doctor's office to ask this of your insurance company). If you feel your neurologist doesn't know all of these things about you I suggest that you be proactive and fill in any blanks. The final choice is yours With all of that knowledge, you can probably narrow down the most appropriate DMT candidates for you to three or four. Then it's time for your neuro to clearly explain why those are the best choices and to review the pros and cons of each. Then, and only then, it's time for you to make the final choice. And your decision might be not to use any medication. That wouldn't be my choice, but it might be yours. After all, you're the one who'll be living with whatever choice you make. What has been your experience? Was your neurologist helpful when selecting a DMT or were you given "a handful of brochures" and told to do-it-yourself? How did you choose? You're invited to visit my personal blog at www.themswire.com.
Immune system activation induced by filgrastim may be beneficial for patients with progressive multifocal leukoencephalopathy associated with the use of Tysabri (natalizumab), without worsening multiple sclerosis (MS) progression, a study says. The study with that finding, “Treatment of natalizumab‐associated PML with filgrastim,” was published in…
The relative risk of developing cancer was found to be higher in multiple sclerosis (MS) patients who more frequently switched between disease-modifying treatments, according to a study. In addition, researchers found an increased incidence of cancer in male MS patients from 20 to 50 years old, and in female…
Human Blood-brain Barrier in a Chip, Created in the Lab, May Help Design New Therapies, Study Shows
By tweaking stem cells in a laboratory, researchers were able to generate a model of the human blood-brain barrier (BBB) in a chip. The BBB is a highly selective barrier that is damaged in multiple sclerosis (MS), allowing immune cells to reach the central nervous system and damage…
A new artificial intelligence (AI)-based model is better than conventional methods for detecting brain changes in response to treatment with Tysabri (natalizumab) in patients with relapsing-remitting multiple sclerosis (RRMS), a study reports. The study, “High-dimensional detection of imaging response to treatment in multiple sclerosis,” was published in…
A clinical trial based at the Cleveland Clinic and the University of Nottingham, U.K., is recruiting patients with relapsing-remitting multiple sclerosis (RRMS) to compare two treatment strategies, the National Multiple Sclerosis Society announced. The Phase 4 study, called DELIVER-MS (NCT03535298), intends to enroll about 800…
Startup company Oscine Therapeutics has received an investment from Sana Biotechnology to support the research and development of cell-based therapies for a variety of neurological disorders, including multiple sclerosis (MS). This venture is based on work done over the past several decades in the lab of Steve…
Aubagio (teriflunomide), an approved medicine for relapsing forms of multiple sclerosis (MS), specifically targets highly metabolic and more autoreactive T-cells, analysis of the Phase 3 TERI-DYNAMIC clinical trial data shows. The findings, contrary to expectations, support a selective effect of Aubagio on different T-cell populations. The study “Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects” was published in the Science Translational Medicine journal. In MS, immune cells, or lymphocytes known as T-cells, attack and destroy myelin, the fat-rich substance that wraps around nerve fibers (axons). Myelin loss creates lesions that affect nerves of the brain and spinal cord. Previous evidence suggested that T-cells, depending on their active or resting state, rely on specific ways of energy production or metabolism. Aubagio, marketed by Sanofi Genzyme, is a well-known inhibitor of a mitochondrial enzyme called dihydroorotate dehydrogenase (DHODH), that is crucial for the activity of T-cells. However, how Aubagio selectively targets the autoreactive T-cells is poorly understood. To shed light on this matter, an international group of researchers used data from the TERI-DYNAMIC clinical trial that tested Aubagio in patients with relapsing form of MS to better understand how the therapy inhibited the patients' self-immune responses. The Phase 3, open-label TERI-DYNAMIC trial (NCT01863888) included 70 patients from Belgium, Germany, and The Netherlands, aged 18 to 56. Participants received Aubagio as a 14 milligram (mg) once-daily, oral dose, and researchers assessed the changes in immune cells' profile up to 24 weeks. Results showed that, contrary to what was expected, Aubagio was not generally decreasing T-cell levels in treated patients. Instead, it significantly reduced a particular subset of T-cells, called "Th1 helper cells." Moreover, researchers found that the diversity of T-cell receptors — the surface proteins that can recognize a particular antigen (a protein that can elicit an immune response) — making T-cells specific to a certain target was reduced in MS patients after treatment with Aubagio. These findings suggested that some T-cells were particularly susceptible to Aubagio. Using a mouse model for MS, the experimental autoimmune encephalomyelitis (EAE) model, researchers showed that the CD4+ T-cells (helper T-cells) and CD8+ T-cells, those that reacted most strongly against self-antigens, were the most sensitive to DHODH inhibition by Aubagio. Moreover, researchers saw that Aubagio was not affecting the production of pro-inflammatory molecules — called cytokines — at the cell level, but their overall decrease probably was due to the reduction in T-cell numbers. In line with these findings, CD4+ T-cells that produced the cytokine interferon gamma were significantly reduced with Aubagio treatment, whereas CD4+ T-cells that produced interleukin 17A were unchanged. This suggests that Aubagio is able to interfere with specific sub-types of immune cells. When the team compared the metabolic profile of T-cells from healthy subjects with that from patients with relapsing-remitting MS (RRMS) in both remission and in relapse phases, they found that the metabolism of T-cells from the last group was significantly altered, and thus targetable. Altogether, the results suggested that T-cells with a high-affinity to self-antigens are more susceptible to inhibition of the DHODH enzyme by Aubagio. “Therapeutic targeting of metabolic alterations might represent an attractive concept in MS, and might represent an as yet unrecognized key mechanism of teriflunomide-mediated immune modulation in this disease,” the researchers concluded.
FDA and EMA to Review Ozanimod as Possible Oral Therapy for Relapsing MS Another disease-modifying therapy (DMT) is a step closer to gaining approval for use both in the U.S. and in Europe. And that’s good news. The discouraging news, however, is that once again, the approval is being…
Exosomes — tiny vesicles secreted by cells — collected from bone marrow stem cells and injected into a mouse model of multiple sclerosis (MS) helped to treat the disease, a study reports. Specifically, this treatment eased myelin loss and neuroinflammation in the mice, and improved motor function, the…
The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) both agreed to review for possible approval ozanimod, Celgene‘s investigational oral therapy for relapsing forms of multiple sclerosis (MS). An FDA decision on the company’s New Drug Application for ozanimod is expected on…
AxoSim Licenses Mini-Brain Technology, Which May Speed Therapy Discovery for Neurological Diseases
AxoSim has acquired exclusive rights to lab-grown brain miniatures, coined “Mini-Brain,” a technology developed at Johns Hopkins University that uses stem cells to create models of the human brain in a dish. This technique may help speed therapy discovery for many neurological diseases, including multiple sclerosis…
Cyxone Nears First-in-human Trial for Investigational Preventive MS Treatment T20K Multiple sclerosis can be treated but it can’t be prevented — at least not yet. But these researchers hope that a substance derived from a natural plant protein called T20K will be able to ease or even prevent MS…
Mavenclad (cladribine) may surpass Gilenya (fingolimod) in the category of oral disease-modifying therapy (DMT) of choice for the treatment of multiple sclerosis (MS) in Canada, according to a press release. The Canadian healthcare market for MS has grown considerably over the past two years. In November…
Targeting the excessive activation of immune cells called neutrophils, and the associated oxidative stress, may be a therapeutic strategy in patients with multiple sclerosis (MS), according to a mouse study. The study, “Deficiency of Socs3 leads to brain-targeted EAE via enhanced neutrophil activation and ROS production,” was…
Cyxone submitted an application to the Netherlands research ethics committee to start the first clinical trial in humans testing T20K, its investigational preventive treatment for multiple sclerosis (MS). Approval by the Netherlands regulating authority…
The latest research in multiple sclerosis (MS), along with the most recent advancements in treatment strategies and comprehensive care, will be presented at the Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, which beings today. Running through June 1 at the Washington State Convention Center in Seattle, the…
The first patient has been dosed in a Phase 2B clinical trial evaluating the safety, efficacy, and tolerability of SAR442168 in people with relapsing multiple sclerosis (MS). SAR442168, formerly known as PRN2246, is being developed by Principia Biopharma, in collaboration with Sanofi Genzyme, for MS and other central nervous…
Early, positive safety results from a Phase 1 trial testing a potential immunotherapy, ATA188, in people with progressive multiple sclerosis will be detailed at the 5th Congress of the European Academy of Neurology (EAN) late next month, its developer, Atara Biotherapeutics, announced. ATA188 is an investigational and “off-the-shelf”…
Simvastatin, a widely prescribed statin that works to lower cholesterol levels, may slow brain atrophy and disease progression in people with secondary progressive multiple sclerosis (SPMS) for reasons unrelated to changes in blood cholesterol, a new analysis of a Phase 2 clinical trial reports. These findings are in…
Pear Therapeutics, in collaboration with Novartis, has launched a study evaluating the clinical use of Pear-006, its software-based prescription digital therapeutics (PDT) product for treating depression symptoms in people with multiple sclerosis (MS). PDTs belong to a new class of treatment strategies in healthcare intended to treat diseases,…
Investigational therapy evobrutinib, also known as M2951, can reduce relapse rates and brain lesions in people with relapsing forms of multiple sclerosis (MS), 48-week data from a Phase 2 clinical trial suggest. Updated results from the trial (NCT02975349) were presented at the recent 2019 annual…
Out-of-pocket costs for medications treating neurological diseases have skyrocketed over the last 12 years in the U.S., with multiple sclerosis (MS) patients, especially, paying 20 times more in 2016 than they were in 2004, a study reported. “Given the high costs of…
At the 2019 annual meeting of the American Academy of Neurology (AAN), Multiple Sclerosis News Today sat down with Bernd Kieseier, MD, global head of multiple sclerosis at Biogen, to discuss the company’s portfolio, latest data, and therapeutic development plans in the field of multiple sclerosis (MS). Kieseier said…
Two ongoing clinical trials may help doctors better understand which type of disease-modifying therapy — those considered highly effective or those with low-to-moderate efficacy used in an escalating treatment approach — would be best for people in the early stages of relapsing-remitting multiple sclerosis (RRMS), according to a …
Although the use of highly effective disease-modifying treatments (HETs) in patients with relapsing-remitting multiple sclerosis (RRMS) has increased, they still represent a minority among the treatment strategies used, according to a study. The study, “Trends in the use of Highly Effective Disease Modifying Treatments in Multiple Sclerosis…
Treatment with Ocrevus (ocrelizumab) decreases the levels of neurofilament light chain (NfL) and immune B-cells in the serum and central nervous system of patients with relapsing multiple sclerosis (MS), according to results from a Phase 3 trial. The research, “Ocrelizumab treatment reduced levels of neurofilament light chain and…
After first rejecting it due to cost-effectiveness concerns, the National Institute for Health and Care Excellence (NICE) has now approved the use of Ocrevus (ocrelizumab) for people in the U.K. with early, inflammatory primary progressive multiple sclerosis (PPMS). This means that PPMS patients living in the…
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