Abstract
The therapy of spinal muscular atrophy (SMA) with a link to 5q chromosome is nowadays a very hot area. A previously casually not treatable disease, it has been in the US since 2016, and in Europe since 2017.
It is newly treatable, and nowadays there are three causal drugs. Two of them, nusinersen (Spinraza) and risdiplam (Ervysdi) increase the synthesis of the SMN protein by modulation of the RNA transcription of the SMN2 gene.
These drugs have to be taken regularly, and are lifelong. The third drug, onasemnogene abeparvovec (Zolgensma) is able to substitute the missing SMN1 gene by a syntetic SMN1 gene delivered by viral vector AAV9.
It is the first systemic gene therapy in medicine. Until now, this drug was taken only once.
There are 4.5 years of data proving its sustaining effect. The first causal therapy was the drug Nusinersen.
It has the huge advantage of 10 years' experience with a high number of treated patients, more than 10,000. This drug does not go through the cerebro-spinal barrier, due to it having to be applied intrathecaly.
Nusinersen is in CZ reimbursed for all types and ages of SMA patients. Recently, in August 2020, the drug risdiplam was registered in the US.
Its advantage is per oral application; its disadvantage is the short experiences and limited acces in CZ. Risdiplam is not yet registered in the EU, due to this it is available only through the early access program for SMA patients type 1 and 2.
The third causal therapy, and second registered drug in the EU, is onasemnogene abeparvovec. Due to the systemic delivery this therapy is limited only for children before the age of 3 years and weighing less than 13.5 kg.
Besides, the already registered therapies there are many clinical trials with experimental drugs ongoing - many neuroprotective drugs and muscle strength-enhancing compounds. The actual therapy cannot help with all the symptoms of the disease, it can only mildly improve the motor function and primarily slow down the progression.
Due to this, there is still a need for multidisciplinary symptomatic care that should be provided in Neuromuscular Centres.