Carnegie Mellon's Stefan F. Zappe is using adult neural stem cells to develop a new drug therapy that may help treat a variety of genetic disorders, such as Hunter syndrome.
Zappe, an assistant professor of biomedical engineering, and graduate student Sasha Bakhru are creating genetically engineered adult neural stem cells — programmed to produce an essential missing protein — that can be delivered to patients' brains.
In Hunter syndrome, for example, patients are lacking the enzyme called "iduronate-2-sulfatase," which helps cells break down certain waste products. One in every 130,000 boys is born with the rare but deadly genetic disorder.
Zappe, who is working with Dr. Raymond Sekula, a neurosurgeon at Allegheny General Hospital and a Tepper School MBA flextime student, said he selected adult neural stem cells for his work because they can be harvested from a patient's brain, have the potential to be multiplied outside of the body, can be genetically engineered, can disperse within the brain once re-implanted and can replace all major cell types of the brain.
Once the brain has healed from the initial implant of the encapsulated stem cells, the stem cells are genetically engineered to produce an enzyme that eats the microcapsule, freeing the neural stem cells. The stem cells can then migrate deep into the surrounding brain tissue where they provide the missing enzyme.
"We are particularly interested in targeting the brain because this area of the body is protected by the so-called blood-brain barrier that has been very difficult to penetrate with therapeutic enzymes that are usually injected into the patient's bloodstream," Zappe said.
According to Sekula, Hunter syndrome is a devastating illness that affects more than 500 children in the U.S. alone. Over time, toxic waste products accumulate in the cells of the body, and, although progression of the disease varies, the majority of children die in their teens.
"If we can reliably provide the missing enzyme iduronate-2-sulfatase to the central nervous system of these children, we may change the course of this disease," Sekula said. "Our technology and methodology also will likely have far-reaching implications for hundreds of other diseases of the central nervous system."