Spinal muscular atrophy
Spinal muscular atrophy (SMA) is one of the most common genetic causes of infant death. We developed a gene therapy approach preclinically, now enabling children with SMA to achieve developmental milestones where they previously would have declined.
What causes SMA?
Spinal muscular atrophy (SMA) is a form of motor neuron degeneration that usually starts during foetal development and is one of the most common genetic causes of infant death. SMA is caused by autosomal recessive mutations in the survival motor neuron (SMN) gene resulting in reduced SMN protein levels. On the basis of the age of onset and the severity of the disease, four clinical subtypes have been described. The most severe form, type 1 SMA, is a devastating childhood condition (also known as Werdnig-Hoffmann disease or "floppy baby syndrome"), which is generally fatal by three years of age.
SMN replacement gene therapy for SMA
Prof Mimoun Azzouz and Prof Pam Shaw developed a gene therapy to restore the missing SMN protein using a self-complementary adeno-associated virus (scAAV9) that crosses the blood-brain barrier and allows fast, robust and long-lasting gene transfer.
They demonstrated that a single intravenous injection of scAAV9-SMN rescued the lethal phenotype in the established SMNΔ7 mouse model of SMA and robustly increased survival of the SMNΔ7 mice from 14 days to more than 300 days. The SMN replacement gene therapy received orphan drug status from the European Medicines Agency (EMA). Clinical trials conducted in the USA using the same approach led to Zolgensma® being approved as a disease modifying therapy, now available in four NHS Trusts including 91Ö±²¥ Children’s Hospital for infants under 13 months.