Implications of the First Ex Vivo Gene Therapy Approved for Treating Early-Onset Metachromatic Leukodystrophy

Abstract

Laura Campbell from Orchard Therapeutics, London, UK, opened the session by explaining the objectives of the symposium and providing some background information on metachromatic leukodystrophy (MLD). MLD is a rare and life-threatening inherited disease of the body’s metabolic system. MLD is caused by a mutation in the ARSA gene, which results in the accumulation of fats called sulfatides in the brain and other areas of the body, including the liver, gallbladder, kidneys, and spleen. Over time, the nervous system is damaged and children with MLD experience progressive neurological symptoms, including motor, behavioural and cognitive regression, severe spasticity, and seizures. Patients with MLD gradually lose the ability to move, talk, swallow, eat, and see. MLD is estimated to occur in approximately one in every 100,000 live births.1,2 The prognosis for MLD is extremely poor. Most children within the late infantile (LI) form die by the age of 5 years; the juvenile (JU) form progresses to death within 10–20 years; and those affected by the adult form typically die 25 years following the onset of symptoms.1 Approval of Libmeldy (atidarsagene autotemcel, [arsa-cel]; Orchard Therapeutics, London, UK), a gene therapy containing an autologous CD34+ cell enriched population, which contains haematopoietic stem and progenitor cells transduced ex vivo using a lentiviral vector encoding the human ARSA gene, for the treatment of early-onset MLD,3 opens up tremendous new possibilities for eligible children with MLD faced with this devastating disease, where previously no approved treatment options existed. Libmeldy is the first product approval for Orchard Therapeutics, a global gene therapy leader dedicated to rare diseases through the development of gene therapies.4 Francesca Fumagalli from the Paediatric Immunohematology Unit and Department of Neurology, Ospedale San Raffaele – Telethon Institute for Gene Therapy (OSR-TIGET), Milan, Italy, shared the evidence on the efficacy and safety of Libmeldy in patients with MLD. The clinical trial investigating Libmeldy started more than 10 years ago at OSR-TIGET. Campbell closed the symposium by providing several educational resources to support clinicians managing children with MLD.