An early-onset, fatal neurodegenerative disease can be prevented in the womb in mice by delivering gene therapy vectors into the fetal brain, reports a paper published online this week in Nature Medicine.
Gaucher disease is an inherited condition that results in the swelling of the liver and spleen, bone fragility and pain, anaemia, fatigue and susceptibility to bruising. These symptoms result from the buildup of fatty chemicals that the body would normally break down. Although the symptoms of some mild forms of Gaucher disease can be treated postnatally with enzyme replacement therapies, more severe forms that cause irreversible early-onset, neurodegeneration are currently untreatable and are often fatal. This prognosis suggests that potential treatments need to be initiated as early as possible.
Simon Waddington and colleagues surgically deliver a viral vector engineered to widely re-express the gene encoding an enzyme that is deficient in Gaucher disease into a fetal mouse’s central nervous system. Mice treated in the womb with this vector exhibit less brain degeneration and survive considerably longer than untreated mice. As a step towards clinical application, the authors also developed methods to use ultrasound to guide the delivery of similar viral gene transfer vectors into the larger brains of nonhuman primates in the womb.
Further research is needed to determine the degree to which the delivered vectors continue to be expressed across the target animal’s lifespan, especially in the larger central nervous system of nonhuman primates. In addition, gene therapy approaches like these will require early and accurate diagnoses of prenatal disease.