Nasal Foralumab for the Treatment of Progression Independent of Relapses in Patients With Nonactive Secondary Progressive Multiple Sclerosis
Neurology Neuroimmunology & Neuroinflammation, 2026
Chitnis T., Singhal T., Zurawski J., Saraceno T., Gopalakrishnan N., Cain L., LaBarre B., King D., Bergmark R., Maxfield A., Cicero S., Pan H., Dubey S., Vaquerano S., Hansel C., Healy B., Saxena S., Lokhande H., Baharnoori M., Madill E., Sheth M., Rodin R., Ye J., Clementi N., Clementi W., Weiner H.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology | Pathophysiology | Serum |  Olink Target 48 |
Abstract
Background and Objectives
Progression independent of relapses (PIRA) is a major therapeutic challenge in multiple sclerosis (MS). Nasal anti-CD3 treats animal models of progressive MS by inducing regulatory T cells (Tregs) that suppress CNS inflammation and lessen clinical disease.
Methods
Ten patients with nonactive secondary progressive MS (naSPMS) that continued to progress on B-cell therapy were treated with nasal anti-CD3 (foralumab) for a minimum of 6 months in an open-label study. Safety monitoring included otolaryngology evaluation and neurologic assessments including Expanded Disability Status Scale (EDSS), MS Functional Composite, Modified Fatigue Impact Scale (MFIS), California Verbal Learning Test, and Low Contract Visual Acuity. MRI and microglial translocator protein (TSPO)-PET imaging with [F-18]PBR06 were conducted. Serum and CSF proteomic biomarkers and single-cell RNA sequencing of blood were performed to evaluate foralumab-induced immunomodulation. The end points of our study were safety, clinical effects, microglial signal, and immune measures.
Results
Our clinical observations were that all patients stabilized on EDSS scores and 3 of 4 patients treated continuously for 12 months had improvement on EDSS. Six of 10 patients had improvement in fatigue on the MFIS scale. There were no treatment-related serious adverse events or severe AEs, and no new T2 lesions were observed on MRI. There was a reduction in TSPO-PET signal over 6 months (p < 0.05). Changes in peripheral blood gene expression occurred as early as 3 months and affected antigen presentation, interferon responses, and regulatory pathways in multiple cell types including FoxP3+ Tregs, CD4+ Tcm cells, CD8+ Tem cells, CD14+ and CD16+ monocytes, and B cells. TGFβ expression was increased across multiple cell subsets.DiscussionThese findings identify a novel, nontoxic immune based therapy for the treatment for PIRA that acts by the induction of a regulatory immune responses and dampens microglial inflammation. Double-blind placebo-controlled trials are warranted to explore nasal foralumab for the treatment of naSPMS.