Research professor Mayland Chang is taking to heart the maxim "a mind is a terrible thing to waste" in two ways, as she uses her mind to the fullest by working to develop a treatment for traumatic brain injury (TBI).
Chang, director of the Chemistry-Biochemistry-Biology Interface (CBBI) Program, said she and other researchers have been studying a group of 27 enzymes called Matrix metalloproteinases (MPPs) for more than a decade. She said the team has found a promising use for one of these enzymes, Matrix metallopeptidase nine (MPP-9), in treating TBI.
"We thought that this group of enzymes would be important for many diseases. Not much was known, so we started making inhibitors," Chang said. "It turns out MPP-9 plays a critical role in the pathology of TBI."
Chang said every case of TBI essentially can be divided into two injuries, each with different effects.
"You have the primary injury, the blow to the head," Chang said. "There is absolutely nothing you can do for the brain cells that die in the primary injury. This is followed by a cascade of events, starting with damage to the blood-brain barrier, that result in the secondary injury. The secondary injury is linked to long term problems, including coma and death."
MPP-9 contributes to the secondary injury by cleaving tau proteins, so inhibiting MPP-9 can prevent the cascade of events leading to the secondary injury, Chang said.
Chang said she has personal reasons for seeking an effective TBI treatment. Her mother passed away as a result of a severe TBI in 1997 at the age of 70, having slipped and hit her head on her patio. Chang said she is also motivated by the threat of TBI her son faced as a competitive snowboarder.
Chang said no therapeutics for TBI currently exist because of the nature of the condition and reluctance on the part of pharmaceutical companies.
"There are no existing therapeutics for TBI because of the difficulty of getting compounds through the brain-blood barrier and because TBI is an acute condition and 'big pharma' is more interested in chronic conditions. ... Big pharma is not really working on diseases like this," she said.
Chang said her research group has been fortunate that the compounds they use effectively cross the blood-brain barrier, something more than 98 percent of drugs are incapable of doing.
"It's very challenging for drugs to cross the barrier and reach therapeutic concentration," she said. "We are lucky with the compounds we have, which are able to cross the barrier on their own."
Chang said one of the biggest challenges has been maintaining this quality while also making the compounds more water-soluble. Water solubility enables the compounds to be injected, which is important, given that many patients with TBI are unconscious or otherwise unable to swallow.
The most recent version of the treatment compound is working in animal models, specifically, mice, in terms of both water solubility and penetrating the blood-brain barrier, Chang said.
Contact Christian Myers at cmyers8@nd.edu
