In the first clinical trial involving gene therapy for an adult neurodegenerative disorder, dying cells in the brains of Alzheimer's patients sprouted new connections, according to a new study in JAMA Neurology.
During a three- to four-hour surgical procedure, 10 patients were injected with genes modified to express nerve growth factor, which promotes axonal growth in certain cells of the brain. Axons are the brain's information superhighways, the white matter that connects neurons. The target of the injections was the basal forebrain, located at the bottom, front part of the brain, an area that is important to maintaining attention, motivation, memory and behavior and that is usually affected early in Alzheimer's patients.
The trial patients were all in the early to early-mid stages of the disease and lived an average of 5.4 more years. At death, their brains were then autopsied.
"Up to this point, we hadn't known whether growth factors could effect degenerating neurons of Alzheimer's brains," said Mark Tuszynski, director of the Center for Neural Repair at the University of California-San Diego School of Medicine and the study's lead author. "All the 10 patients showed growth factor response. ... Cells that had clearly been in the process of dying were regrowing axons."
The results of the trial confirmed that the therapy was safe, which was the principal goal of the Phase 1 trial. But the bonus, Tuszynski said, was that the researchers learned "very unequivocally that degenerating neurons can respond."
What they did not learn, he said, was whether those restored neurons would improve the clinical symptoms of Alzheimer's patients. That's the focus of a phase 2 clinical trial currently taking place at the University of Southern California.
One of the upsides to gene therapy treatment is that it is targeted and can be restricted to specific, affected areas of the brain without damaging healthy cells nearby. But Tuszynski is also excited about the one-and-done aspect of the treatment.
"With gene therapy, the potential is you can go in and have a surgical procedure of three to four hours and have lifelong protection, without having to take a drug every day," he said. "If you know you have a disease that robs you of the essence of your intellect, will you undergo a three-hour operation? Pardon the expression, but that seems like a no-brainer."