Mapping the differences in care for 5,000 Spinal Muscular Atrophy patients, a survey of 24 national registries in North America, Australasia and Europe

Abstract

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder characterised by the degeneration of motor neurons and progressive muscle weakness. It is caused by homozygous deletions in the survival motor neuron gene on chromosome 5. SMA shows a wide range of clinical severity, with SMA type I patients often dying before 2 years of age, whereas type III patients experience less severe clinical manifestations and can have a normal life span. Here, we describe the design, setup and utilisation of the TREAT-NMD national SMA patient registries characterised by a small, but fully standardised set of registry items and by genetic confirmation in all patients. We analyse a selection of clinical items from the SMA registries in order to provide a snapshot of the clinical data stratified by SMA subtype, and compare these results with published recommendations on standards of care. Our study included 5,068 SMA patients in 25 countries. A total of 615 patients were ventilated, either invasively (178) or non-invasively (437), 439 received tube feeding and 455 had had scoliosis surgery. Some of these interventions were not available to patients in all countries, but differences were also noted among high-income countries with comparable wealth and health care systems. This study provides the basis for further research, such as quality of life in ventilated SMA patients, and will inform clinical trial planning.

Nusinersen for SMA: expanded access programme

“…Globally, however, there are differences regarding the level of ventilatory and nutritional support provided to patients with SMA type 1 16. We describe transformations in optimal multidisciplinary care accompanying active therapy and increased complexity of clinical decision making.…”

The impact of integrated omics technologies for patients with rare diseases

“…Patient registries, for example, are important tools for collecting phenotypic and natural history data from patients across multiple centres and countries, and in rare disease these have proved to be crucial tools for gaining knowledge about disease progression, survival, care outcomes and response to therapy as well as finding particular subsets of patients for recruitment into clinical trials. Examples include the long-running registries for lysosomal storage diseases such as Fabry, Gaucher and Pompe disease, which have collected extensive clinical data supporting research into these conditions and assessing therapeutic response [43], or the TREAT-NMD registries for DMD [44] and spinal muscular atrophy [45], which have collected data on over 10,000 DMD and 3000 spinal muscular atrophy patients and enabled recruitment into clinical trials. However, the proliferation of registries for individual rare diseases and relative lack of interoperability of datasets means that here, too, harmonisation is required, and this is being addressed by a number of initiatives including RD-Connect and the European Commission itself through its Joint Research Centre in Ispra, Italy [46].…”

SMN regulation in SMA and in response to stress: new paradigms and therapeutic possibilities

“…Cold-shock suppresses transcription and may also be associated with oxidative stress due to associated changes in reactive oxygen species (Al-Fageeh and Smales, 2006). A large collaborative study analyzed the differences in care for SMA patients in North America, Australasia, and Europe (Bladen et al 2014). Within the data from this study, Tsai et al identified a correlation between climate and SMA type III ambulation, in which regions with cooler climates (Germany/Austria, Switzerland, and the UK) have patients with a more extended period of ambulation than those in countries with warmer climates (Argentina, Hungary, Ukraine, and Serbia) (Tsai et al 2016; Bladen et al 2014).…”

“…A large collaborative study analyzed the differences in care for SMA patients in North America, Australasia, and Europe (Bladen et al 2014). Within the data from this study, Tsai et al identified a correlation between climate and SMA type III ambulation, in which regions with cooler climates (Germany/Austria, Switzerland, and the UK) have patients with a more extended period of ambulation than those in countries with warmer climates (Argentina, Hungary, Ukraine, and Serbia) (Tsai et al 2016; Bladen et al 2014). The interpretation of this data by Tsai et al did not take into consideration differences in health care systems of these countries or dietary or cultural considerations that may also contribute to the phenotypic severity (Tsai et al 2016).…”