Gene therapy treats deadly Gaucher disease in the womb

Gene therapy has successfully treated a disorder in mice while still inside the womb, according to a study published in Nature Medicine. 

'For many genetic diseases, the damage starts early,' said lead author Dr Simon Waddington, acting director of the EGA Institute for Women's Health at University College London. His team aims to make them treatable early, too. 

They used experimental fetal gene therapy on mice with type 2 Gaucher disease (GD). People with this condition have a faulty gene so they cannot make a working enzyme to break down a type of fatty molecule. Without it, the fatty molecule accumulates in the brain and other organs, causing damage. 

Type 1 Gaucher disease is treated with regular injections of the missing enzyme, but the more damaging type 2 is currently untreatable, because the brain's protective barrier prevents the enzyme from entering. The experimental therapy exploits the fact that the blood-brain barrier in a fetus has not yet fully formed, making it easier to get molecules into the brain. 

'Even one day after birth, it's harder to get into the brain' said study co-author Dr Jerry Chan, associate professor and senior consultant, KK Women's and Children's Hospital, Singapore. 'This new approach will bring hope, not only for Gaucher disease, but also for other inborn errors of metabolism that can potentially be treated using fetal gene therapy.'

The team used a virus vector to carry a functioning copy of the gene, and performed a single injection into fetal mice in the womb. The treatment was effective when delivered into the brains of mice, as well as the blood.

This effectively rescued the mice from paralysis and death by 15 days after birth. However, they still weighed less than normal mice, couldn't move as well, and had some brain inflammation. 

The team also trialled the injections immediately after birth. They saw some benefits, but the mice fared less well than the ones who had been given injections in utero.

'It is really impressive. From a technical standpoint it is almost bulletproof,' says Professor W. Mark Saltzman, department chair of biomedical engineering at the Yale School of Engineering and Applied Science, who was not involved in the study. 

The team is now working on developing the therapy as part of a joint venture with other universities and drug companies, with the aim of potentially testing it in humans.

However, Dr Raphael Schiffmann, medical director at the Baylor Institute of Metabolic Disease in Dallas, said that 'it is not clear how relevant this is going to be to human disease'. Gaucher disease is not commonly included in prenatal tests, and the treatment carries risks for the mother. Those who are tested for Gaucher disease typically have a family history and would, therefore, have the option to use preimplantation genetic screening when planning their families.