Specialized adeno-associated virus for central nervous system gene therapy

Background

Unlike other cell types in the human body, nerve cells (neurons) have an extremely limited ability to replace themselves through division following damage to the nervous system. Most injuries and diseases of the central nervous system (CNS) involve damage to axons, the protrusions from neuron bodies that transmit signals through the body. Therefore, many injuries to the CNS involve the severance of axons leaving the neuronal body still viable.

Although it has been discovered that it is possible to induce axonal regeneration in damaged neurons through the targeting of specific molecular pathways, there are difficulties delivering gene therapy molecules to the bodies of damaged neurons. This is due to the blood-brain barrier (BBB) and the blood-spinal cord barrier (BSCB), the specialized barriers which control the flow of molecules between the blood and the CNS. It is therefore impossible to delivery gene therapy molecules through systemic blood administration and is necessary to find other ways of delivery genetic molecules. Direct administration to the trauma site or through injection into the brain or spinal cord also faces challenges such as the inability to reach all the damaged neurons, and complications arising from the difficulty of the injection procedure.

Technology Overview

Boston Children’s Hospital researchers have developed another mode of transducing the gene therapy molecules into neurons. Adeno-associated viruses (AAVs) can be used as molecular vectors for gene therapy, and the researchers of this invention were able to successfully engineer a strain of AAV that can cross the BBB and BSCB following an injury or neuronal damage by selectively targeting the affected CNS region through IV injection, with promising results for the possibility of recovering neuronal damage following spinal cord traumas or other CNS damaging conditions.

Benefits

• The first technology with unique and promising therapeutic effects through the regeneration of axons while they are still viable soon after injury
• The AAV design provides selective targeting of neurons after intravenous injection, sparing other cells in vital organs like liver and heart, reducing the possibility of adverse effects.
• Treatment is able to pass the BBB and BSCB.

Applications

• Treatments to relieve paralysis and other neuronal conditions following spinal cord injury
• Reduction of neuronal damage following traumatic brain injury
• The possibility of recovering sight after a traumatic optic nerve injury
• With further development, the ability to induce brain neuronal recovery after brain damaging conditions such inflammation or ischemia following stroke