Method for Delivery to the Brain of Plasmid DNA Encoding Therapeutic Proteins for CNS Disorders

INV-1262

Background

Neurodegenerative diseases are debilitating diseases that impose significant financial and social impact and burden. The prevalence of these diseases, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, is progressing at an alarming rate in the aging population. If left unchecked, more than 12 million Americans will suffer from neurodegenerative diseases by 2030.

Gene therapy can be a potential therapy for the treatment of neurodegenerative diseases however, drug delivery to the central nervous system (CNS) faces the challenge of crossing the blood brain barrier (BBB). Intracranial injection of therapeutics delivered by viral vectors has been proposed to overcome BBB issue however this technique poses safety risks such as potential damage to the brain tissue, hemorrhage, immunological reactions to the viral vector, infection, and trauma related to brain surgery. Furthermore, the injection only treats the cells in the area of injection, and multiple injections for the treatment of a wider area are needed, which increase the risk of brain trauma and hemorrhage. Hence, there is a need for methods and formulations which obviate the use of viral vectors and direct-injection methods.

Technology Overview

Researchers at Northeastern developed effective methods and agents for gene delivery to CNS. In this method, the gene-therapy agent is delivered by nanoparticles and administered intranasally as droplets or aerosols. The gene-therapy agent can be of different properties, including plasmid DNA and anti-sense RNA. The nanoparticle can be conjugated with poly cations such as poly lysine and polypeptides with neuroprotective properties that promote recovery of the neural injury. The ratio of nucleic acid content to nanoparticle can be tuned and varied depending on the needed effective dose.

This method of delivery enables administering multiple doses or sustained doses within minutes to hours in a course of treatment. The method also improves the transit and expression of gene therapy and contributes to better treatment outcomes. This invention not only overcomes the current limitations of gene therapy for neurodegenerative diseases but also can be effectively used for the treatment of other CNS disorders.