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Nanoformulated Recombinant Human Myelin Basic Protein and Rituximab Modulate Neuronal Perturbations in Experimental
Muhammed A Saad1,2, Noha M Eissa2, Mohammed A Ahmed3
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
A novel nanoformulation combining myelin basic protein and rituximab (Nano-rhMBP-RTX) effectively reduced multiple sclerosis symptoms in mice. This treatment improved behavior, reduced inflammation, and preserved neural tissue in an experimental autoimmune encephalomyelitis model.
Area of Science:
- Neuroscience
- Immunology
- Biotechnology
Background:
- Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.
- Rituximab (RTX) and recombinant human myelin basic protein (rhMBP) have shown efficacy in MS symptom management.
- Developing advanced drug delivery systems is crucial for enhancing therapeutic outcomes in MS.
Purpose of the Study:
- To synthesize and evaluate a novel nanoformulation (Nano-rhMBP-RTX) for potential neuroprotective effects.
- To compare the efficacy of Nano-rhMBP-RTX with individual components (rhMBP, RTX) and empty nanoparticles in an MS model.
- To investigate the impact of Nano-rhMBP-RTX on clinical, behavioral, biochemical, and histopathological parameters in experimental autoimmune encephalomyelitis (EAE).
Main Methods:
- Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice using myelin oligodendrocyte glycoprotein (MOG) and complete Freund's adjuvant (CFA).
- Mice were treated with rhMBP, RTX, empty poly(lactide-co-glycolide) nanoparticles, or the Nano-rhMBP-RTX formulation after disease onset.
- Clinical scores, body weight, behavioral tests, and biochemical markers (e.g., IFN-γ, IL-10, TNF-α, BDNF) were assessed. Histopathological analyses were performed.
Main Results:
- The Nano-rhMBP-RTX group exhibited significant reduction in clinical scores and improved behavioral responses compared to other groups.
- Histopathological examination revealed reduced neuroinflammation and preserved tissue integrity in Nano-rhMBP-RTX treated mice.
- Biochemical analysis showed elevated levels of IL-4, CNP, and TGF-β, alongside decreased levels of NF-kB and TNF-α in the Nano-rhMBP-RTX group.
Conclusions:
- The developed Nano-rhMBP-RTX formulation demonstrated significant neuroprotective effects in the EAE mouse model.
- This nanoformulation effectively ameliorated disease symptoms by normalizing behavioral changes and modulating key biochemical markers.
- Nano-rhMBP-RTX holds promise for the treatment of multiple sclerosis, offering improved myelination and reduced tissue damage.
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