Other
Although the heart is not a matter of routine concern, a link between SMA and certain heart conditions has been suggested.Children with SMA do not differ from the general population in their behaviour; their cognitive development can be slightly faster, and certain aspects of their intelligence are above the average. Despite their disability, SMA-affected people report high degree of satisfaction from life.Palliative care in SMA has been standardised in the Consensus Statement for Standard of Care in Spinal Muscular Atrophy which has been recommended for standard adoption worldwide. Prognosis
In the absence of pharmacological treatment, people with SMA tend to deteriorate over time. Recently, survival has increased in severe SMA patients with aggressive and proactive supportive respiratory and nutritional support.If left untreated, the majority of children diagnosed with SMA type 0 and 1 do not reach the age of 4, recurrent respiratory problems being the primary cause of death. With proper care, milder SMA type I cases (which account for approx. 10% of all SMA1 cases) live into adulthood. Long-term survival in SMA type I is not sufficiently evidenced; however, as of 2007 advances in respiratory support seem to have brought down mortality.In untreated SMA type II, the course of the disease is slower to progress and life expectancy is less than the healthy population. Death before the age of 20 is frequent, although many people with SMA live to become parents and grandparents. SMA type III has normal or near-normal life expectancy if standards of care are followed.
Its development was discontinued in 2018 in view of competition from nusinersen and underwhelming data from an open-label extension trial.Of clinically studied compounds which did not show efficacy, thyrotropin-releasing hormone (TRH) held some promise in an open-label uncontrolled clinical trial but did not prove effective in a subsequent double-blind placebo-controlled trial. Riluzole, a drug that offers limited clinical benefit in amyotrophic lateral sclerosis, was proposed to be similarly tested in SMA; however, a 2008–2010 trial in SMA types 2 and 3 was stopped early due to the lack of satisfactory results. Other compounds that displayed some neuroprotective effect in in vitro research but never moved on to in vivo studies include β-lactam antibiotics (e.g., ceftriaxone) and follistatin. Muscle restoration
This approach aims to counter the effect of SMA by targeting the muscle tissue instead of neurons. Reldesemtiv (CK-2127107, CK-107) is a skeletal troponin activator developed by Cytokinetics in cooperation with Astellas. The drug aims at increasing muscle reactivity despite lowered neural signalling. The molecule showed some success in phase II clinical trial in adolescent and adults with SMA types 2, 3, and 4. Apitegromab (SRK-015) is monoclonal antibody that blocks the activation of the skeletal muscle protein myostatin, thereby promoting muscle tissue growth. As of 2021, the molecule showed success as an experimental add-on treatment in paediatric and adult patients treated with nusinersen. GYM329 (RO7204239), developed by Hoffman-La Roche, works similarly to apitegromab by blocking myostatin activation. As of 2022, it is undergoing clinical development in non-ambulant children with SMA aged 2–10, combined with risdiplam.