David Williams, MD, the principal investigator of the clinical trial, discusses gene therapy and its impact on children with adrenoleukodystrophy
Adrenoleukodystrophy — depicted in the 1992 movie “Lorenzo’s Oil” — is a genetic disease that most severely affects boys. Caused by a defective gene on the X chromosome, it triggers a build-up of fatty acids that damage the protective myelin sheaths of the brain’s neurons, leading to cognitive and motor impairment. The most devastating form of the disease is cerebral adrenoleukodystrophy (CALD), marked by loss of myelin and brain inflammation. Without treatment, CALD ultimately leads to a vegetative state, typically claiming boys’ lives within 10 years of diagnosis.
Mitochondria, as you may know, are the engines that power cells. They’re always in motion, supplying energy wherever it’s needed. In brain cells, mitochondria especially have to hoof it around, traveling out into the axons and dendrites to fuel the energy-intensive task of communicating with other cells.
But in at least one form of Parkinson’s disease, that movement becomes a problem: the genetic mutations causing the disease leave neurons unable to make the fidgety organelles hold still. Without this ability, the dopamine-producing neurons in the brain’s substantia nigra can’t safely dispose of mitochondria when they go bad, and the neurons die or become impaired.
“When damaged, mitochondria produce reactive oxygen species that are highly destructive, and can fuse with healthy mitochondria and contaminate them, too,” explains Tom Schwarz, of the F.M. Kirby Neurobiology Center at Children’s Hospital Boston, senior investigator on a study published in Cell today. “It’s the equivalent of an environmental disaster in the cell.” …