Spinal cord injuries (SCIs) cause paralysis and loss of feeling in some or most of the body. Many people with SCIs are permanently disabled, relying on wheelchairs and other assistive devices for their entire lives. An estimated 12,000 SCIs occur every year in the United States, and more than 250,000 Americans are living with SCIs. The cost of care for SCI patients is high. The spinal cord consists of bundles of nerve fibers, called axons, that carry signals up and down the spinal cord and to the rest of the body. Complete recovery from SCI is normally not possible because these axons are usually damaged and cannot regrow in adults. The investigators are working on a drug that stimulates spinal cord axon growth and restores neurological function after SCI. This project’s aim is to further develop this therapy to prepare it for testing in human clinical trials.
Axerion is developing a therapeutic protein, Nogo Receptor Decoy [NgR(310)ecto-Fc], to promote the recovery of neurological function through axonal fiber growth after SCI. In nearly all neuropathies, a substantial portion of brain and spinal cord is preserved. If the remaining healthy tissue can be “rewired” with appropriate axonal connections, improved neurological function can occur.
Partial recovery from SCI may take place within the first few weeks after the injury. Additional recovery beyond that period is limited. This is because axonal growth, which is needed for greater recovery, is virtually nonexistent in the adult spinal cord. Treatment for chronic SCI, therefore, consists primarily of physical and/or occupational therapy. To date, no therapeutic approved by the Food and Drug Administration (FDA) promotes new connections between surviving nerve cells. As a result, a significant unmet medical need exists for therapeutics that stimulate neurological recovery.
It has been demonstrated that NgR(310)ecto-Fc stimulates corticospinal and raphespinal axon growth. Additionally, it has been shown that functional recovery can be achieved in acute, subacute and chronic spinal contusion injuries with NgR(310)ecto-Fc therapy. Pre-clinical studies that demonstrate efficacy in an animal model of chronic SCI provide the basis for launching clinical trials of NgR(310)ecto-Fc therapy.
The goal of this project is to execute key activities necessary to support an Investigational New Drug (IND) application to the FDA, with clinical trials for the treatment of chronic SCI initiated soon afterward. The ultimate goal is to allow victims of chronic SCI to regain function and to improve their quality of life.
Axerion Therapeutics, Inc., Branford, Connecticut
George D. Maynard, Ph.D.
Public Health Impact
Axerion Therapeutics will develop Nogo Receptor Decoy to promote the recovery of neurological function through growth of axonal fibers after SCI. The NgR(310)ecto-Fc protein blocks the action of myelin inhibitors and allows axonal growth and functional recovery in rodent models.
Approved studies are ongoing.
- Synthesis of Good Manufacturing Practice (GMP) material
- Formulation development
- Pharmacokinetic/absorption, distribution, metabolism, and excretion (PK/ADME) studies
- IND-directed toxicology