Gene Therapy for Babies with Severe Spinal Muscular Atrophy

A 5-month old baby boy called Arthur, diagnosed with the devastating condition of spinal muscular atrophy, has become the first patient to be treated in the United Kingdom by the National Health Service with a new gene therapy.

Spinal muscular atrophy, SMA for short, affects around 1 in every 10,000 births and is the result of mutations in a gene called SMN1. It is an inherited disease and babies born with it have mutations in both of their copies of the SMN1 gene. The absence of a functional SMN1 gene means they cannot make the corresponding protein.

Their parents will be healthy carriers with one normal SMN1 gene and one mutant copy, and it is this mutant copy which they will both have passed on to their affected child. In the parents, the single normal copy of the gene means that they are able to make the SMN protein in their cells, so they are unaffected. Around 1 in 50 of the population have a single SMN1 gene mutation and will be unaware of it, unless they have children with someone who also has such a mutation. Even then, their children have only a 1 in 4 risk of suffering from SMA. So nearly all the SMN1 gene mutation carriers in the population will be quite unaware of the danger to their children lurking in their mutated version of this genes. There is unlikely to be any family history of this condition amongst their relatives.

The affected children, lacking a normal functional SMN1 gene, are unable to make the SMN protein. Its absence causes the motor nerve cells emerging from their spinal columns to begin to die. These are the cells which control the movement of muscles, and as they die the muscles become progressively unresponsive and weaker. Babies with the most serious form of SMA face a short and limited existence. These babies are unable to sit up, and lose the ability to move their limbs and heads. Eventually the muscles needed for breathing begin to fail, and very sadly these children are unlikely to survive until their 3rd birthdays.

In 2019, the US Food and Drug Administration approved a gene therapy developed by Novartis for use in babies with severe SMA. Other jurisdictions have now followed suite. This involves infusing the children with a harmless virus modified to carry a normal copy of the SMN1 gene. Once these viruses have entered the baby’s cells, the SMN protein can be made, and the motor nerve cells will cease dying. Nearly all of the children in the clinical trials of this gene therapy have shown benefits, being able to breathe unaided at 14 months of age, and with a half of them able to sit independently at 18 months. Some treated children have reported even better responses. At present is too soon to be able to report the long-term outcomes of this treatment.

Now that we have an effective, if highly expensive treatment, it is important to diagnose SMA children as early as possible. Usually they are diagnosed at around  3 months of age onwards, when they fail to achieve the normal developmental milestones in mobility, such as reaching to grasp objects. The issue here is that once an affected child has been born, motor nerve cells are being lost steadily, and they cannot be replaced. A number of countries already use a genetic test to screen all babies at birth for SMA, and the pressure is now on for this to be adopted more widely, so as to maximise the benefits of this new gene therapy.

©CC Rider

2nd Jun 2021

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