Cellular therapeutic for neurorepair in progressive multiple sclerosis
Novel hematopoietic stem cell-based delivery of an NgR1 antagonist fusion protein (NgR(310)ecto-Fc) to promote neurorepair and limit axonal damage in progressive multiple sclerosis. Validated in EAE models showing enhanced clinical recovery.
Overview
Axonal damage and loss are the primary drivers of irreversible neurological disability in progressive multiple sclerosis (MS). This research program targets the Nogo-A/NgR1 signaling axis, a pathway implicated in axonal injury during neuroinflammation, by developing a novel cellular therapeutic that delivers a NgR1 antagonist fusion protein directly to demyelinating lesions. The approach uses hematopoietic stem cells (HSCs) as living carriers of the therapeutic NgR(310)ecto-Fc protein, enabling targeted delivery to sites of active demyelination and promoting both axonal preservation and remyelination.
Technical specifications
Core innovation:
- HSC-based cellular delivery platform engineered to express and secrete the NgR(310)ecto-Fc fusion protein at inflammatory demyelinating lesions
- NgR1 antagonism blocks Nogo-A-mediated inhibitory signaling, limiting axonal degeneration
- Published data demonstrates that HSC-delivered NgR(310)ecto-Fc promotes remyelination and clinical recovery in the MOG35-55-induced EAE model
- Validated recovery from peak EAE symptoms (clinical scores of 3) at Day 30 in NgR(310)ecto-Fc HSCT recipient mice compared to control groups
Future validation plans:
- Differentiating the contribution of endogenous microglia versus transplanted monocytes in therapeutic delivery and myelin debris clearance
- Timed ablation of NgR1 within the CNS to dissect its role in axonal degeneration initiation and axonal preservation during inflammatory demyelination
- Demonstrating generation of new myelinating oligodendrocytes from adult OPCs during therapeutic delivery in innate demyelination models that mimic smoldering lesions of progressive MS
Technology readiness level
The therapeutic platform has demonstrated proof-of-concept efficacy in the MOG35-55-induced EAE mouse model, with statistically significant clinical recovery observed (P < 0.0001). Ongoing studies are further delineating the cellular mechanisms of repair, including the roles of microglia, transplanted monocytes, and oligodendrocyte precursor cells. The program is at a preclinical stage, with future work aimed at advancing toward translational development for progressive MS.
About Monash University, Melbourne
Monash University is a comprehensive public research university and one of Australia’s largest, known for scale, interdisciplinarity, and an applied orientation. Its Melbourne-based technology precinct brings together university laboratories, pilot-scale and prototyping suites, and company R&D groups alongside government research organizations to enable co-development and rapid iteration. Integration with a major hospital network supports clinical trials and translation, while structured industry placements and doctoral partnerships create a robust talent pipeline for corporate R&D. Research is backed by competitive funding from the Australian Research Council, the National Health and Medical Research Council, and state and federal programs that incentivize industry collaboration. A dedicated technology transfer office manages IP, licensing, and startup formation, with pathways to incubation and investment within the precinct.
delivered to your inbox.