Conjugates of saponin and antisense oligonucleotides for use in the treatment of neurodegenerative diseases

Abstract

The present invention relates to the fields of therapy and drug delivery. More specifically, disclosed herein are therapeutic methods and pharmaceutical compositions for treating disorders of blood-tissue barrier-shielded organs that harbour substantive populations of post-mitotic neurons, such as the organs derived from neural tube that include the central nervous system and the eye. The disclosed methods and compositions involve localised administration into such organs of an effector component that targets an intracellular biological target, in combination with a saponin component that enhances effective uptake of the effector component into the cells and / or that enhances effective routing of the effector component inside the cells where the biological target is present. For example, the effector component can be an oligonucleotide therapeutic that is targeting a gene product associated with the disorder of the CNS and / or of the eye. Due to cellular uptake-stimulating and / or endosomal escape enhancing effects of the saponin component, the presented herein neuropharmaceutical and ophthalmic compositions for the localised administration into the CNS and / or into the eye, respectively, can be formulated with lower concentrations of the effector component and / or at lower volumes, which confers safety-benefits to the neurons and to the comfort of the patient.

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