University researchers have found a way to stimulate the production of a clotting agent in blood cells that might someday help hemophiliacs produce the protein they need but don’t have.
Hemophiliacs are prone to excessive bleeding and joint problems because they lack the protein called factor VIII.
Robert Hebbel, a University Medical School researcher, said mice in the study that received genetically engineered human blood cells continued generating them in the spleen and marrow long after they were injected.
Blood: Journal of the American Society of Hematology published the study in mid-January.
Hebbel said the manipulated cells produced several hundred times more factor VIII than he expected.
While many other researchers are also experimenting with gene therapy, none have been successful in treating hemophilia.
Hemophilia is presently treatable reactively, but nothing addresses DNA, the disease’s cause.
Hebbel said his lab has produced levels of factor VIII exceeding those in human trials by other labs. However, he said, the other labs are working with humans and his lab is still working with animals.
His lab’s approach uses a non-viral method. Some gene therapy involves placing DNA into modified viruses, which are then inserted into the body. The viruses then attach themselves to cells and insert the DNA.
This poses a problem that Hebbel said his experiment avoided – sometimes patients have reactions to the virus.
His lab’s method uses chemicals to weaken the cell’s wall so researchers can “tease” the DNA in the cell before it enters the blood stream.
Sometimes with gene therapy, the cells silence the foreign DNA, either immediately or after only a few weeks, Hebbel said.
The mice Hebbel and his researchers used didn’t encounter that problem. They continued to produce high levels of factor VIII throughout the experiment, Hebbel said.
It might be luck, but it could also be the types of cells they are using, he said. His lab used endothelial cells, which don’t naturally produce suitable amounts of factor VIII.
He said he doesn’t know if the approach will work in humans, and it will be several years before human trials are conducted.
“It’s one of these things where it’s a very exciting result, but we’re a long way from curing anybody with it,” he said.
His lab is now working with dog cells to determine the feasibility of canine trials with hemophiliac dogs, which could begin this year.
Katherine High, a University of Pennsylvania medical school professor, said while Hebbel’s research is still in earlier stages of development than the work of other researchers, it doesn’t preclude him from having a more successful treatment someday.
She said Hebbel’s approach is unique because of the type of cells his lab has modified and the fact that they are produced outside the body and injected into the bloodstream.
But she said plenty of questions must still be answered. For example, she said the factor VIII didn’t plateau in the study but instead continued to increase.
Hebbel said this happened with some mice, while others maintained a level amount of factor VIII. He said he hopes further research will reveal the reason.