Special Lecture Ludo van der Pol

Ludo van der Pol
Department of Neurology and Neurosurgery; Netherlands SMA Center; UMC Utrecht

Professor Ludo van der Pol (Neurologist, UMCU) will present the 5-year experience with Spinal Muscular Atrophy (SMA)-gene therapy based on minimally-invasive adeno-associated viral (AAV)- vector-mediated delivery of the SMA gene to SMA-patients.

Location: Colloquium Room NIN Meibergdreef 47 Amsterdam

Host: Joost Verhaagen (j.verhaagen@nin.knaw.nl)

Title: Gene-based therapies for neuromuscular disorders. Lessons learned from spinal muscular atrophy (SMA).

Abstract of lecture:

Pediatric neuromuscular disorders are hereditary disorders that cause severe disability
and shortened life spans. Changes in more than 300 genes are responsible for the large variety of neuromuscular disorders (NMD), which are all rare. Hereditary proximal spinal muscular atrophy (SMA) is one of the more common pediatric NMD, with an estimated incidence of 1:10.000 newborns per year (i.e. 15-20 new cases per year in the Netherlands). It is the most common genetic cause of infant mortality and childhood disability and is caused by the homozygous deletion of the survival motor neuron (SMN1) gene on chromosome 5q. SMN protein has a range of basic cellular functions, but its deficiency primarily causes dysfunction and premature death of alpha-motor neurons in the spinal cord and consequently severe muscle weakness of bulbar, axial, respiratory and proximal limb muscles. The wide range of severity is primarily explained by copy number variation of the highly homologous SMN2 gene, which is unique to humans and ensures the production of low levels of SMN protein in the absence of SMN1. The genetics of SMA have triggered the development of no less than three SMN-augmenting drugs: AAV9-based SMN gene therapy and two SMN2 splicing modifiers. Combined with the recent addition of SMA to neonatal screening programs, these therapies have changed the perspective of newborns and to a lesser extent children and adults with SMA. High prices have triggered societal discussions of cost-efficacy. The 5-year experience of SMA treatment will be presented, including the lessons learned and their relevance for other neuromuscular disorders and rare diseases.