Penta-MS Platform for Multiple Sclerosis

Disease Background: Multiple sclerosis is an immune-mediated neurological disorder where the immune system acts on the fatty sheath - myelin sheath. Lymphocytes turn autoreactive and cross the blood-brain barrier resulting in local inflammation of the central nervous system with demyelination, gliotic scarring, and subsequent axonal loss. Symptoms initiates with focal sensory disturbances, vision loss in certain cases, weakness of the limbs, gait disturbances with bowel or bladder symptoms. The disease progress with a relapsing remitting course. Tissue injury patterns show oligodendrocyte loss, selective destruction of small-caliber axons, astrocytic gliosis, and demyelination. Demyelination is followed by neurodegeneration with the involvement of various components of adaptive and innate immunity that lead to a diverse pattern of inflammatory injury in the CNS.

 

Details on the Model:  Pentagrit multiple sclerosis animal model is a Transient receptor potential melastatin 2 (TRPM2) mutant with the increased production of CXCL2 chemokine developing a pathophysiology leading to neutrophil infiltration with subsequent demyelination and immune activity on the brain and spinal cord. The model displays optic neuritis, vertigo, motor symptoms, limp ataxia and other sensory symptoms.  Mycophenolate Mofetil approved by the FDA as an immunosuppressant for a wide range of graft rejection rescues gait, progressive weakness of limps therefore slowing down the course of pathology in multiple sclerosis zebrafish.