Following a series of outstanding discoveries, five Western University of Health Sciences faculty are developing a “magic molecule” with the potential to treat traumatic brain injury, stroke, glaucoma, and disorders associated with learning impairment.
Graduate College of Biomedical Sciences (GCBS) Dean Michel Baudry, PhD is leading a team that includes College of Osteopathic Medicine of the Pacific (COMP) Professor Xiaoning Bi, PhD, MD, GCBS Assistant Professor Steve Standley, PhD, GCBS Research Assistant Professor Yubin Wang, PhD, and College of Pharmacy Assistant Professor Lyna Luo, PhD.
“In the brain there are two major isoforms of this enzyme, calpain-1 and calpain-2,” Baudry said. “Calpain-1 and calpain-2 play opposite functions in both synaptic plasticity and learning and neurodegeneration. Calpain-1 is required for triggering synaptic plasticity and learning and memory. Calpain-2 limits the extent of synaptic plasticity and learning and memory. Calpain-1 is neuroprotective and calpain-2 is neurodegenerative.”
Baudry and his team have identified a selective calpain-2 inhibitor, named NA 101, which is both neuroprotective and a cognitive enhancer when injected into mice. They tested NA 101’s neuroprotective effects in two models – acute glaucoma produced by a transient increase in intraocular pressure, and traumatic brain injury. When injecting this molecule two hours after increasing intraocular pressure, it protected retinal ganglion cells from dying and protects vision. They had similar positive results with traumatic brain injury.
“We gave this magic molecule one hour after this insult, and we protected about 75 percent of neurons, which will die otherwise, and decreased brain lesion by 75 percent,” Baudry said. “This is a degree of protection that I’ve never seen in the literature. We have really strong data showing that by blocking this calpain-2 enzyme we prevent the death of neurons.”
Baudry and his WesternU team have joined forces with two business people, Dr. Bernard Malfroy-Camine (CEO, MindSetRx, MA) and Greg DiRienzo (CEO, ProgenaCell, CA), to form NeurAegis, a company that will develop the molecule. Baudry and his team filed a patent through WesternU claiming that selective calpain-2 inhibitors can enhance learning, be neuroprotective, and can be a useful treatment of a large number of diseases. NeurAegis and WesternU have agreed on the terms of an exclusive licensing agreement allowing NeurAegis to develop these molecules for the many possible indications. Under this agreement, WesternU becomes a shareholder of the company and is entitled to royalties generated from direct or indirect sales of NeurAegis products.
Aegis is the shield of the Greek god Zeus, so NeurAegis is focusing on neuroprotection. The company is the result of 35 years of research on the calcium-dependent protease calpain by Dr. Baudry and his collaborators.
“All of us are very excited about this, because creating NeurAegis not only crowns 35 years of basic research, but also fits perfectly with the translational strategy Western University of Health Sciences has been embarking on in recent years,” Baudry said.