Gene therapy for rare brain disease shows promise in early clinical trial

Children with a fatal brain disorder showed significant improvements after receiving gene therapy in an early-stage clinical trial.

Canavan disease is a rare genetic condition mainly affecting infants and young children, causing severe developmental delays, neurological difficulties, and reduced life expectancy. A mutation in the ASPA gene disrupts the function of oligodendrocytes: cells that make the protective myelin that insulates nerve fibres. All eight participants enrolled in this clinical trial showed increased myelin volume on brain scans and a significant improvement in developmental milestones compared with the typical course of the disease.

'In 25 years working with this patient population, I have never seen more impressive results,' said Paola Leone, professor of cell biology at Rowan University in Glassboro, New Jersey, and lead author of the study published in Nature Medicine. 'Their quality of life has completely changed.'

The trial used a new form of gene therapy designed to deliver a healthy copy of the gene directly and exclusively into oligodendrocytes. Earlier attempts targeting other types of brain cells failed to show any improvement in the condition.

'For the first time, we're seeing clear biological and functional evidence that gene therapy targeting oligodendrocytes can directly address the core pathology of this disease,' said Dr Michael Muhonen, co-chief medical officer of Myrtelle, the company behind the clinical trial.

The treatment was well tolerated by all participants, with no serious side effects linked to the therapy. There are no disease-modifying treatments available for Canavan disease, and current therapies are supportive only. The US Food and Drug Administration has already given the drug fast-track designation, and the UK's Medicines and Healthcare products Regulatory Agency has granted admission to the innovative licensing and access pathway.

Myrtelle plans to keep monitoring the patients to assess the long-term efficacy while working to make this therapy more widely available. 'This is not the end but the beginning of a new era in the treatment of neurological disorders,' said Professor Leone.