Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05994950 |
| Other study ID # |
RL1 874 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
December 6, 2023 |
| Est. completion date |
December 31, 2024 |
Study information
| Verified date |
April 2024 |
| Source |
Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust |
| Contact |
Professor Tracey Willis |
| Phone |
01691404047 |
| Email |
tracey.willis1[@]nhs.net |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
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.
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?
