INTRANASAL NANOSYSTEMS FOR SPINAL MUSCULAR ATROPHY (SMA) THERAPY

Spinal Muscular Atrophy (SMA) is a rare genetic disorder of childhood onset and currently has no cure. It is caused by mutations in the survival motor neuron 1 (SMN1) gene and the inability of its paralog, SMN2, to compensate for SMN protein production [1]. Consequently, reduced SMN protein expression leads to motor neuron degeneration and progressive muscle atrophy, often resulting in premature death. Present pharmacological approaches include gene therapies, neuroprotective agents, and protein stabilizers [2]. However, the central nervous system (CNS) uptake of some of these drugs is limited by the blood-brain barrier (BBB). Our study proposes the development of liposomal nanoparticles (LNPs) for the intranasal administration of indoprofen and olesoxime in the SMA treatment. LNPs loaded with olesoxime were synthesized via solvent injection, yielding nanoparticles with an average size of approximately 60 nm, a polydispersity index of 0.3, and a surface charge close to neutrality, physicochemical properties suitable for intranasal delivery [3]. In addition, we will evaluate the toxicity of NPLs using a hybrid neuroblastoma cell line, while also assessing its internalization efficiency and drug synergy in enhancing SMN protein expression in a cell model that mimics the disease. This nanosystem represents a promising strategy for combined and localized therapy, providing a safe and effective treatment approach for SMA.