Evrysdi (Risdiplam) is the first oral gene therapy medication approved to treat SMA. In order to understand the treatment, it is necessary to know something about SMA.
SMA is a genetic condition caused by the loss of specialized nerve cells, called motor neurons that control muscle movement. Once these nerves die, the muscles become weak and atrophy (when muscles get smaller). SMA can affect a child’s ability to crawl, walk, sit up, and control head movements. Severe SMA can damage the muscles used for breathing and swallowing. Although most individuals with SMA present in infancy, the disease can also present in childhood or adulthood for the first time.
SMA is caused by genetic faults in a gene called SMN1 (survival motor neuron 1). Almost all patients have the identical genetic fault – both copies of the SMN1 gene are deleted (missing). It is not clear why there is then such variability in the age of onset. One partial explanation for the variability (and relevant to some of the new therapies) is that all individuals have another nearly identical gene to SMN1 called SMN2. This gene is not critical for nerve cell survival, but may be present in variable copy number in different individuals. As a broad principle, individuals with more SMN2 gene copies (2-3) have milder SMA disease than people with less SMN2 (1-2) gene copies). This is because the SMN2 gene can partially compensate for the absence of SMN1 (although not entirely). Importantly, some of the new therapies available for SMA, including Evrysdi (Risdiplam), are designed to cause the SMN2 genes to produce more of the missing SMN1 protein and thus make the disease less severe. The more SMN2 genes an individual has, the better the drug works.
Gene therapy is a technique that modifies a person’s genes or genetic material to treat or cure genetic disease. Gene therapies can work by several mechanisms and need to be tailored to the individual disease mechanism., The broad principle would be to recover the function of critical proteins that are encoded by a gene. What the therapies cannot do is to recover permanent damage eg motor neurons that have already lost function entirely. Some gene therapies are only given once, whereas others require repeated doses, and the oral therapy may be life-long.
In SMA, to date, three forms of gene therapy have been developed. They are all very expensive and thus availability and accessibility remain challenging. All have been shown to have positive outcomes, especially when initiated early in the disease, ideally presymptomatically. The analyses of different patient subgroups showed that motor function was generally improved in younger individuals and stabilized in older individuals over trial periods, usually of up to 1-2 years. These drug treatments could significantly change the disease trajectory from the known natural course of SMA. Trials in presymptomatic individuals have shown that the start of symptoms is delayed significantly. There are no long term studies yet to show how long this effect lasts.
Evrysdi (Risdiplam) is now approved in the US and available in South Africa for pediatric and adult patients with SMA of all ages. It is an oral solution containing a small-molecule compound that modifies SMN2 pre-mRNA splicing and increases SMN1. This medicine is given once a day; dosing is dependent on age and body weight. Side effects are reported. It is currently contraindicated in pregnancy and breast feeding women and may cause infertility in males.
As the best responses have been seen in individuals started on therapy pre-symptomatically, this raises the importance of early diagnosis. This would need to be achieved by screening all newborns followed by early treatment with new drugs as the standard of care for SMA. Importantly although the new drugs like Risdiplam do not cure the disease, it is necessary to continue developing new drugs or experimenting with drug combinations. It is not yet clear whether patients who have had one drug therapy could easily switch when improved therapies are developed. The release of the first oral gene therapy for SMA is an exciting development as we enter a new phase of therapy, but many questions remain about long term benefits and side effects. Accessibility and cost remain challenging. Drug developments are likely to progress with time, and we can hope that these will eventually lead to the ability to completely alleviate the disease symptoms and progression.
Good day
My son is 11weeks old, he was diagnosed with sma 1, the doctors says he has +-6months. Can anyone help
Good day,
You have to speak to your son’s neurologist for medication and treatment, unfortunately we can not help with the medical side.
How do we get access to the medication?
You should speak to your neurologist about this. Your neurologist will need to apply to your medical aid for approval of the SMA treatment/medication.
Please note that the treatment is very expensive and should not be stopped once started, as stopping the medication can lead to progression of the condition. Your medical aid will usually review the approval every six months to determine whether the treatment should continue.
Good day,
The treatment for SMA is very expensive and needs to be continued. Unfortunately, if the medication is stopped, SMA will start to progress again.