A Review of the Management and Outcomes of Children With SMA in the West Midlands During 2017-2022

Spinal Muscular Atrophy Clinical Trial

Official title: A Review of the Management and Outcomes of Children With SMA in the West Midlands During 2017-2022

Status Recruiting

Clinical Trial Summary

Spinal Muscular Atrophy (SMA) is a rare neuromuscular condition, characterised by loss of motor neurons as a result of a mutation in the survival motor neuron gene. This results in muscle wasting and in the most common and severe type, death before 24 months. Over the recent years there has been a dynamic shift in the therapeutic options for these patients involving both approved therapies, including gene therapy, and access to clinical trials in genetic modifying. As a result of this mortality and morbidity have changed particularly for the SMA type 1 population and therefore there is now a changing phenotype with many children needing interventions at different time points compared to the natural history. This review process is a retrospective review from 1st July 2017 - 30th June 2022, when most of the new drug therapies were being introduced, of all the children aged from 0-16 years in the West Midlands region and their outcomes.

Clinical Trial Description

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder characterized by degeneration of alpha motor neurons in the spinal cord resulting in progressive muscle wasting, weakness, and paralysis, often leading to early death. It occurs in approximately 1 in 10,000 births. The carrier frequency is variable (between 1:38-1:50) but thought to be highest in Caucasian and Asian populations. The most common form of SMA is due to a genetic defect in the survival motor neuron 1 (SMN1) gene located on Chromosome 5 (5q11.2-q13.3) which encodes SMN, a protein widely expressed in all eukaryotic cells and necessary for survival of motor neurons. Whilst the diagnosis is made by genetic testing after clinical suspicion, classification is made clinically and on what level of function is achieved, at what age. The severe neonatal type (SMA 0) and the common severe type (SMA I), accounting for approximately 50% cases, presenting before the age of 6 months. These infants, treatment naïve, are very weak and never achieve independent sitting. The rare SMA 0 group generally presents in the neonatal period, often with extreme weakness and contractures and most die within the neonatal period. SMA type II patients present between 6-18 months can achieve independent sitting but are unable to stand and walk and have a reduced life expectancy. SMA type III can be very variable ranging from children who have a similar neuromuscular disability to those with type II, to those that are mildly affected. SMA type IV, the mildest form and very rare, presents in adulthood with onset usually after the second decade, with normal life expectancy. Whilst the sub-groups are classified clinically, there does appear to be a relationship between clinical severity and functional SMN protein and SMN2 copy number. This being said, there has been a phenotypic change since the introduction in the of disease modifying treatment over the last 5 years and therefore the historical classical classification will be evolving. Whilst clinicians have not seen a type I phenotype change to a type II phenotype, many have seen significant changes in mortality and morbidity for these children. The principle question is how are the West Midlands cohort progressing? ;

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy

• NCT number: NCT05994950
• Study type: Observational
• Source: Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust
• Contact: Professor Tracey Willis
• Phone: 01691404047
• Email: tracey.willis1@nhs.net
• Status: Recruiting
• Start date: December 6, 2023
• Completion date: December 31, 2024