carSpinal cord injury is a devastating condition that generally results in sensory and motor paralysis below the level of the injury. More than 12,000 individuals in the United States per year suffer spinal cord injuries from motor vehicle accidents, falls, sports accidents, or other causes. Despite the serious nature of spinal cord injury and potential for therapeutic benefit, there are no drugs on the market to repair neuronal damage and reduce paralysis after spinal cord injury.

Intrinsic Barriers to Regeneration

Intrinsic barriers to regeneration  prevent robust regeneration after spinal cord injury. Intrinsic barriers to regeneration reflect mechanisms related to a diminished capacity of older axons to regenerate as part of a developmentally programmed process that occurs in development and aging. The most important target to overcome the intrinsic barriers to axon regeneration is a protein called PTEN. Experimental knockdown of PTEN in preclinical models stimulates robust regenerative axon growth. However, until now, therapeutically relevant strategies to knock down PTEN expression to promote axon regeneration have not been developed. BioAxone has created a novel self-delivering RNA interference technology (sdRNA) to knock-down expression of PTEN in adult neurons. The lead drug candidate is called BA-43407.

Extrinsic Barriers to Regeneration

Axons in the central nervous system (CNS) can regrow after injury when treated with drugs that promote regeneration. Axon regeneration is blocked, in part, by extrinsic barriers to regeneration. BioAxone’s CEO, Dr. Lisa McKerracher (then at McGill University) led the first group to purify and identify a protein in myelin called MAG with regeneration blocking activity. Since that time, a wealth of growth inhibitory proteins that block regeneration in the CNS have been identified. Some investigators have developed compounds that block individual growth inhibitory protein or their receptors. BioAxone took a different strategy and developed a compound that acts on a convergent point of signaling for all growth inhibitory proteins, a signaling protein called Rho. See this link for a review by the Christopher Reeve Foundation. The drug that was developed from this approach, BA-210, is a Rho inhibitor that could offer both a regenerative and neuroprotective activity after an acute spinal cord injury.  BA-210 has shown hints of  efficacy in Phase 2 studies. There are no clinical trials currently ongoing with this compound.