Richa Kulshrestha
Robert Jones and Agnes Hunt Orthopaedic Hospital, UK
Title: Rapid subjective improvement of learning in a patient on Ataluren
Biography:
Kulshrestha works at a centre of excellence for neuromuscular disorders in the UK. She and her team of doctors, physiotherapists and sports scientist are committed to provide innovative methods of rehabilitation of untreatable conditions. This project has the backing of patients and well received by FSHD charity, UK.
Abstract:
Statement of problem: Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal read through of premature stop codons in nonsense mutation genetic disorders. Effectiveness of this drug has been assessed by National Institute of Clinical Excellence in the UK and the drug is available by managed access agreement for patients after 5 years of age. Methodology and theoretical orientation: we describe a patient with Duchenne muscular dystrophy (DMD) commenced on treatment with Ataluren at 5 years and 7 months. Physiotherapy assessments pre and post treatment are compared. Findings: this young boy had global developmental delay and was diagnosed with DMD at two and half years. He started walking at three and half years. He has significant learning difficulties and attends special school. He has point mutation in exon 65 (c.9461T>A; p.Leu3154X) inherited from mother. This is amenable for read through by Ataluren. His muscle biopsy had classic features of dystrophy. Dystrophin was absent with labelling of rod domains and only a rare revertant-like fibres are seen with a C terminal antibody. Mutations towards the C terminus affect all isoforms of dystrophin, including those in the brain. Pre-treatment timed rise from floor was 34.8 seconds, 10 meters run was 11.2 seconds and North Star Ambulatory assessment was 7/34. These responded with 5 months of treatment on Ataluren to timed rise from floor to 11 seconds, 10m run to 8 seconds and North Star Ambulatory assessment to 15/34. According to assessors this difference was related to improvement in understanding of instructions. Conclusion and significance: Effectiveness of Ataluren is proved for motor abilities in patients with DMD. This is the first case subjectively showing that Ataluren can positively impact the learning difficulties.