Nerve Growth Factor given as eye drops in the animal model of multiple sclerosis: prospective study of treatment in early stage of disease

The neurotrophin Nerve Growth Factor (NGF) acts as neuroprotective and neuroreparative agent in pathological conditions affecting CNS structural integrity and functionality. Specifically, NGF administration or transplantation of NGF-producing cells in the brain has prove to reduce disease progression in animal models of Experimental Allergic Encephalitis (EAE) supporting and prospecting the NGF use in the treatment of Multiple Sclerosis. However, the invasiveness of the surgical procedure to injected NGF in brain is unlikely to be feasible in patients who might need early and continuous treatment thereafter for life, and alternative strategies for enhancing endogenous NGF or facilitate NGF penetration in brain might appear more attractive. Recently, NGF applied as eye drops (eNGF) has showed to act in brain and stimulates tissue repair and functional recovery in animal models of brain pathologies. Here the effects of eNGF in the animal model of Experimental Allergic Encephalitis (EAE) in rats is reported. We found that NGF treatment during the first two weeks post EAE induction is able to postpone the insurgence and reduce the clinical score, also affecting the anxiety/depression level. The histological analysis shows reduced signs of inflammation in term of immune infiltrates in the parenchyma and vascular proximity particularly in cerebellum, septo-hippocampal area and periventricolar zones (III and IV ventricles). Reduced expression of inflammatory markers are also found in the brain of EAE rats receiving eNGF. Further, eNGF affects the distribution of neuronal precursors in both EAE and healthy rats. Taken together, these results suggest that eNGF is able to affect the disease development most probably by contrasting the brain inflammatory events, which favor the white and grey matter degeneration also by interfering with neurogenesis and re-myelination