Latest Developments in Multiple Sclerosis Treatment

Programming tissue-sensing T cells that deliver therapies to the brain We created a set of brain-sensing T cells programmed to locally deliver therapeutic payloads customized for cancer or neuroinflammation. First, we identified a set of CNS-specific extracellular ligands using publicly available expression data to establish potential brain “GPS” markers. We identified proteins such as brevican (BCAN), which are components of the brain’s highly unique extracellular matrix and might be exploited for tissue-specific recognition. We screened for antibodies against these CNS-specific antigens and used them to build CNS-activated synthetic Notch (synNotch) receptors, engineered receptors that sense an extracellular antigen and respond by inducing a transcriptional response. To demonstrate the therapeutic potential of this approach, we used this platform to locally induce a set of genetically encoded payloads directed toward different CNS diseases. Brain-sensing T cells that induced CAR expression were able to treat primary and secondary brain cancers, including mouse models of glioblastoma and breast cancer metastases, without off-target attack of tissues outside of the brain. Conversely, CNS-induced expression of the immunosuppressive cytokine interleukin-10 (IL-10) ameliorated neuroinflammation in experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. This tissue-targeted cell induction strategy provides two levels of specificity. First, the cell shows anatomically restricted specificity, as cells are only induced in the CNS, and second, the payload (e.g., CAR, cytokine, antibody) has its own intrinsic molecular targeting specificity. This nested, multiscale targeting strategy mimics the principles of natural biological specificity, avoiding potential unwanted systemic cross-reactions of the molecular payload while focusing its actions more effectively on the target tissue. These results suggest that brain-sensing cells could be used as a general platform to treat a broader set of CNS diseases, including brain tumors, brain metastases, neuroinflammation, and neurodegeneration. Although we focused here on targeting the CNS, this concept could be applied to a broader set of tissues. Tissue-targeted therapeutic cells provide an approach to integrating endogenous and disease signals to generate therapies that are more specific and effective. https://lnkd.in/eY5iwWtw

Parasites can help treat autoimmune and inflammatory diseases. Parasitic proteins with therapeutic potential that can change the treatment of autoimmune and inflammatory diseases, such as Crohn's disease or MS, have been identified by Katarzyna Donskow-Łysoniewska, PhD, Lazarski University. Science in Poland. 16 June 2025 Excerpt: The team led by Katarzyna Donskow-Łysoniewska, PhD, Department of Experimental Immunotherapy at Lazarski University has been studying proteins produced by parasites - intestinal roundworms - for over a decade. The proteins are called mimics. "Mimics imitate human proteins, and their action inhibit excessive reactions of the immune system. They do not exhibit toxicity and a natural effect of evolution. For millions of years, parasites had to learn to survive in the host's body, avoiding attack and burdening its immune system. To do this, they synthesize proteins that imitate natural proteins of the human body, and prevent inflammation', said Donskow-Łysoniewska, in a press release sent to PAP. Per World Health Organization, inflammatory diseases, including autoimmune diseases resulting from excessive and abnormal activity of the immune system, affect over 500 million people worldwide. The diseases include Crohn's disease, multiple sclerosis (MS), and psoriasis. Note: One of the priorities of Donskow-Łysoniewska's team is development of therapy for Crohn's disease - an inflammatory bowel disease that affects millions of people. Based on 2023 and 2024 data, approximately 60,000 people suffer from non-specific inflammatory bowel disease (IBD) in Poland. A subset of 15-20,000 patients struggle with Crohn's disease which most often affects young people. Approximately 70% of patients are under 35 years. The disease was first described in 1904 by Polish physician Antoni Leśniowski. Currently, there is no therapy that would allow a complete cure. Available methods alleviate symptoms, and are associated with side effects, such as weakening effectiveness of the immune system and problems with concentration. 'Our first mimic, we tested on the Crohn's disease model, showed very promising results. The second one, has strong immunomodulatory properties that can be used in the treatment of diseases such as multiple sclerosis and psoriasis. These diseases significantly decrease quality of life of patients and require long-term treatment', the researcher explains. The possibility of offering targeted therapy that does not cause side effects and is safe when used for a long time would be a huge breakthrough in medicine. Katarzyna Donskow-Łysoniewska plans to acquire funding that will allow her team to carry out further work on mimics and conduct preclinical and clinical trials, which may result in the introduction of new therapies. Refer to the enclosed announcement for further information. https://lnkd.in/e_HfuxS6

💡 CAR T cells in autoimmunity: game changer or stepping stone? 👇 What if the same living drugs that revolutionized leukemia treatment could now "reset" the immune system in autoimmunity? 🔍 In a landmark perspective (Blood, April 2025), Mougiakakos, Meyer & Schett explore how CAR T cellS, initially developed for CD19+ B-cell malignancies are redefining treatment paradigms for refractory autoimmune diseases like SLE, systemic sclerosis (SSc), MS, MG & RA 🦠🧬 📌 What sets CAR T cells apart in AIDs? 🔸 Deep depletion in difficult niches: Unlike monoclonal antibodies, CAR T cells actively migrate into inflamed tissues (e.g. kidneys, joints, CNS) and eliminate pathogenic B cells in situ—demonstrated via post-therapy lymph node biopsies. 🔸 Broad target coverage: CD19 CARs deplete B cells from pro-B stage to plasmablasts, covering autoreactive populations missed by CD20 mAbs. BCMA CARs go further—targeting long-lived plasma cells, crucial in diseases with persistent autoantibodies (e.g. anti-dsDNA, anti-Ro, anti-Scl-70). 🔸 Autonomous killing: CAR T cells don’t rely on NK cells, macrophages, or complement—overcoming effector cell dysfunctions often seen in AIDs. 🔸 Therapy-free remission: In 8 patients with SLE, CD19 CAR T-cell therapy induced sustained, treatment-free remission for up to 29 months. 🔸 Promising safety: Severe CRS, ICANS, or prolonged cytopenias are rare—likely due to lower antigen burden vs cancer. Even patients with neuro-AIDs tolerated therapy well. 📈 Expanding the Toolbox 🚀 Dual CARs (CD19 + BCMA) ⬅️ deeper & broader clearance. 🧬 Allogeneic off-the-shelf CAR T cells ⬅️ CRISPR-edited, "fitter" donors. 💉 mRNA-engineered CARs ⬅️ transient expression, no lymphodepletion. 🧘 CAR Tregs & CAAR-T cells ⬅️ restore tolerance without global B-cell depletion. 🔗 Bispecific antibodies (e.g. CD3×CD19 or CD3×BCMA) ⬅️ flexible, scalable alternatives. 🧩 Remaining challenges? ⚠️ Risk of secondary malignancies (e.g. T-cell lymphoma from viral vectors). ⚖️ Access & affordability—AIDs affect up to 10% of the Western population. 🧪 Need for biomarkers to guide personalized cell therapy decisions. 🏥 Scaling capacity without compromising quality. 👩⚕️ As these therapies expand, hematologists & cell therapy specialists must lead multidisciplinary teams to ensure safe implementation in nonmalignant, often young patient populations. 🔗 Read the full perspective: https://lnkd.in/dPS_eDFK #CellTherapy #CART #Autoimmunity #Immunology #Rheumatology #GeneTherapy #Innovation #CellEngineering #TranslationalMedicine

MIT researchers have developed groundbreaking, tiny, wireless devices potentially aiding in the treatment of multiple sclerosis by acting as synthetic myelin that can wrap around individual neurons. These battery-free devices made from a soft polymer, activated by light, can measure and modulate a neuron's electrical activity, enabling thousands to be deployed simultaneously within the body. By tightly conforming to complex cellular structures without causing damage, they offer promising applications for restoring neuron function in damaged axons and modulating electrical activity, possibly revolutionizing treatment approaches for brain diseases. https://lnkd.in/ewd-TUAM https://lnkd.in/eGgGs5TM #india #technology #innovation

Excited to have published a new collaborative paper with the Fournier lab indicating that multiple sclerosis (MS) might be amenable to treatment via epigenetic age reversal Our paper suggests MS accelerates neuronal aging & its reversal via OSK-reprogramming preserves vision in an MS mouse model, suggesting new strategies for treating MS & potentially other neurological diseases. Retinal ganglion cells (RGCs) - in an MS mouse model (EAE) - exhibit aging-like gene expression changes, mirroring neurons from MS patients. Delivering OSK factors (Oct4, Sox2, Klf4) via a domesticated adeno-associated virus (AAV2) reprogrammed neurons — ostensibly to a younger epigenetic state — thereby reducing cell death & preserving visual function in the MS model. These exciting new findings, led by the Fourier lab, are supportive of work we’ve published with Bruce Ksander’s lab @harvardmed on the acceleration of aging due to injury the reversal of blindness in a mouse model of glaucoma & old mice by rejuvenating RGC nerves via OSK (Lu et al., Nature, 2020). We look forward to testing chemical reprogramming factors and seeing the results of human clinical trials using OSK to reprogram RGCs, set to start later this year to treat blindness at Life Biosciences. Work performed at McGill University and Harvard Medical School #medicine #research #ms #multiplesclerosis #neurodegeneration #neuroscience #longevity https://lnkd.in/erddCGbh

"A new type of vaccine developed by researchers at the University of Chicago's Pritzker School of Molecular Engineering (PME) has shown in the lab setting that it can completely reverse autoimmune diseases like multiple sclerosis, type 1 diabetes, and Crohn's disease—all without shutting down the rest of the immune system. A typical vaccine teaches the human immune system to recognize a virus or bacteria as an enemy that should be attacked. The new "inverse vaccine" does just the opposite: it removes the immune system's memory of one molecule. While such immune memory erasure would be unwanted for infectious diseases, it can stop autoimmune reactions like those seen in multiple sclerosis, type I diabetes, rheumatoid arthritis or Crohn's disease, in which the immune system attacks a person's healthy tissues." #vaccine

A three-day skin patch of baclofen can replace the need to take 9-12 tablets for the same duration- a potential alternative for sustained management of multiple-sclerosis-related spasticity. Our recent publication in the International Journal of Pharmaceutics describes this investigation: https://lnkd.in/eXgTh8Fz Great work Gabrielle Verana and Akeemat Tijani