Designing Medicine’s Holy Grail

Naturally occurring biochemicals called growth factor proteins largely dictate who we are as people. They orchestrate embryological development, guide our maturation from infant to adulthood, regulate immune function, direct the ever-changing alterations to our brains that underlie personality and learning, and enable us to repair damage to our bodies or minds. “Effectively and selectively controlling growth factor function is one of the holy grails of medicine,” says Joe Harding, Washington State University professor of physiology and neuroscience.

Too much or too little growth factor action is the hallmark of our most devastating diseases—from cancer, where over-activation of growth factors leads to uncontrolled cell division and the loss of cell adhesiveness associated with metastasis, to neurodegenerative disease where augmented growth factor activity would be helpful in halting degenerative processes and restoring lost mental and motor functions.

But the development of useful, affordable drugs has been difficult. While there have been some notable successes that block specific growth factor systems, these drugs suffer from a lack of specificity, the development of drug resistance, an inability to reach the brain, or exorbitant costs. The ability to activate growth factors with pharmaceuticals has been even less successful, and no FDA-approved drugs are available.

“Our laboratory has developed a technology that targets a process common to many growth factors,” Harding says. “We have successfully built molecules that can either activate or inhibit growth factors. These small molecule drugs are inexpensive to manufacture, highly specific, and can be designed to reach the brain.”

In Harding’s Innovators talk, he will focus on hepatocyte growth factor and its potential to halt and possibly reverse the impact of neurodegenerative diseases.

“We’ve developed a molecule called Dihexa that shows great promise at halting and perhaps reversing the devastating effects of Parkinson’s disease and dementias,” Harding says. “In animals, we are seeing therapeutic effects attributable to a combination of neuro-protection from the offending insult, the generation of new connections among surviving nerve cells, and the production of new nerve cells from stem cells that reside in the brain.”

Harding and his colleagues see potential for this technology to reach far beyond the treatment of neurodegenerative diseases.

“There is a potential here to develop innovative treatments for almost every major human disease,” Harding says, “including cancer, diabetes, and congestive heart failure.”