Development of nanoghosts as targeted therapy for multiple sclerosis

Multiple Sclerosis is the most common inflammatory disease of the central nervous system (CNS), and currently incurable. Mesenchymal stem cells were shown to perform immunomodulatory activities that ameliorate the symptoms of multiple sclerosis¹. However, clinical trials failed to repeat preclinical evidence, perhaps due to host organism derived modifications that reduce the cells’ action in-situ and their blockage by the blood-brain barrier (BBB). We demonstrated how mesenchymal stem cell derived nanoparticles, named NanoGhosts², penetrate the CNS through the blood-brain barrier, based on the assay of in-vitro BBB model, specifically target immune cells at inflammation sites, and treat inflammatory diseases³. Experiments on mice with autoimmune experimental encephalomyelitis (EAE) reveal that the NanoGhosts improve the clinical scoring and prolong the survival of sick mice. The NanoGhosts treated the EAE mice without triggering rejective inflammatory reactions due to their inanimate state and thus immutable biological properties. We developed NanoGhosts that are stimulated to amplify the expression of the immunomodulating glycoprotein CD200 (OX-2). We show the Nanoghosts’ immunomodulatory mechanism in both in-vitro models such as SH-SY5Y and in-vivo EAE. Mice treated with Nanoghosts had higher presence of T cells in the CNS. The Nanoghosts’ multiple dose regimen controls the duration of the therapeutic effect. Our research provides a novel therapy for multiple sclerosis with low adverse effects, thus a lifesaving treatment to patients with multiple sclerosis.

1. Uccelli, A., Laroni, A. & Freedman, M. S. Mesenchymal stem cells for the treatment of multiple sclerosis and other neurological diseases. Lancet Neurol. 10, 649–656 (2011).

2. Toledano Furman, N. E. et al. Reconstructed Stem Cell Nanoghosts: A Natural Tumor Targeting Platform. Nano Lett. 13, 3248–3255 (2013).

3. D’Atri, D. et al. Nanoghosts: Mesenchymal stem cells derived nanoparticles as a unique approach for cartilage regeneration. J. Control. Release (2021). doi:10.1016/J.JCONREL.2021.05.015