Metachromatic leukodystrophy (MLD)
https://academic.oup.com/brain/article-abstract/148/10/3727/8120475?redirectedFrom=fulltext
Metachromatic leukodystrophy (MLD) is a rare genetic condition in which the absence of the ARSA enzyme leads to the buildup of harmful substances (sulfatides) in the brain and peripheral nerves. This study investigated whether arsa-cel gene therapy, which corrects the faulty ARSA gene, can slow or improve the peripheral nerve damage observed in MLD. Researchers followed fifteen children with the late-infantile form of MLD (LI-MLD) who received arsa-cel and compared outcomes to sixteen LI-MLD children who did not receive any treatment. They measured peripheral nerve (motor and sensory) function using electrical tests (nerve conduction velocity, NCV) and monitored ARSA levels for up to eight years after treatment. Although NCVs initially declined, by two years after treatment (around 36 months of age), treated children showed significantly better NCV values in all studied nerves and a slower rate of decline compared to untreated individuals. In the treated group, a younger age at treatment and higher ARSA levels six months post-treatment were associated with better outcomes. Skin biopsy analysis further supported these findings, showing signs of stabilised neuropathy in the treated group. In conclusion, this study focused on the impact of arsa-cel on the peripheral nervous system and found that the therapy improved and stabilised peripheral neuropathy in children with LI-MLD.