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.
Progression from decorticate posturing to decerebrate posturing is often indicative of uncal (transtentorial) or tonsilar brain herniation. Activation of gamma motor neurons is thought to be important in decerebrate rigidity due to studies in animals showing that dorsal-root transection eliminates decerebrate rigidity symptoms. Transection releases the centres below the site from higher inhibitory controls. In competitive contact sports, posturing (typically of the forearms) can occur with an impact to the head and is termed the fencing response. In this case, the temporary posturing display indicates transient disruption of brain neurochemicals, which wanes within seconds. Causes
Posturing can be caused by conditions that lead to large increases in intracranial pressure. Such conditions include traumatic brain injury, stroke, intracranial hemorrhage, brain tumors, brain abscesses and encephalopathy. Posturing due to stroke usually only occurs on one side of the body and may also be referred to as spastic hemiplegia. Diseases such as malaria are also known to cause the brain to swell and cause this posturing effect.Decerebrate and decorticate posturing can indicate that brain herniation is occurring or is about to occur. Brain herniation is an extremely dangerous condition in which parts of the brain are pushed past hard structures within the skull.