Spinal muscular atrophy (SMA) is a genetically determined motor neuron disease affecting people across the lifespan. Although there have been recent preclinical advances in therapeutic strategies, there are no curative treatments available to date. In the absence of pharmacological therapies, clinical ...
(adult onset, with mild motor deficits and normal life span).68Astrocytes seem to be key contributors to the disease, as demonstrated by cell-selective reintroduction ofSMN1gene to globalSMN1-knockout mice. Reintroduction of the gene into motor neurones did not change the pathological phenotype, ...
However, in a severe SMA mouse model, the transgenic expression of PLS3 did not restore motor function or lifespan.65 Another disease modifier identified in at least five asymptomatic indivi duals with an SMN1 deletion and 4 copies of SMN2 is Neurocalcin delta (NCALD), a negative ...
lifespan (type III) and patients that develop symptoms in adulthood (type IV)2. Aberrant expression and/or localization of SMN has also been associated with other pathological conditions including amyotrophic lateral sclerosis (ALS), inclusion body myositis and osteoarthritis12,13,14. Multiple cis-el...
current achievements and future opportunities. We also discuss how these developments are providing important lessons for the emerging second generation of combinatorial ('SMN-plus') therapies that are likely to be required to generate robust treatments that are effective across a patient's lifespan. ...
Background and importance Spinal muscular strophy (SMA) is an autosomal recessive neurodegenerative disorder. SMA I infants have a lifespan of <2 years if not treated. Zolgensma is an innovative drug of gene therapy strategy for SMA patients. Notwithstanding, there remains considerable uncertainty ...
Mutations in ASAH1 have been linked to two allegedly distinct disorders: Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME). We have previously reported FD-like phenotypes in mice harboring a single amino acid s
Sprouting has been difficult to study in severe SMA mice due to their short lifespan. Here, we show that pharmacological SMA mice are capable of terminal sprouting following reinnervation that is largely SMN-C1 dose-independent, but that they display a reinnervation delay that is critically SMN-...
Extraneuronal phenotypes were previously underappreciated, as patients with severe SMA phenotypes usually died in infancy; however, with current treatments for motor neurons increasing patient lifespan, impaired function of peripheral organs may develop into significant future comorbidities and lead to new ...
recessive gene accounts for over 90 per cent of cases [of chronic childhood spinal muscular atrophy], causes a clinical syndrome which manifests its first clinical signs before 5 years of age and in almost all cases before 2 years of age, but which is compatible with life into...