With the publicized announcement on June 1st 2021 that the UK National Health Service had treated a 5 month old baby suffering from a severe form of Spinal Muscular Atrophy (SMA) with Zolgensma, a gene therapy with a list price £1.795million, gene therapies have been widely discussed in the popular media.
The root cause of SMA is an absence of SMN (survival motor neuron) protein, essential to motor neuron cells which control muscle function. Without this protein, the cells die leading to muscle weakness, difficulty in breathing, eating and moving, eventually leading to life threatening conditions in severe forms. Zolgensma is an SMN1 gene enhancing therapy which works by replacing the function of the missing or faulty SMN1 gene which encodes SMN protein with a new, working copy. A virus, adeno-associated virus 9 (AAV9) is the vector which carries the replacement gene into the body and this “infects” the cells with the new DNA, but does not change or become part of the child’s DNA.
Although the concept of gene therapy (i.e. DNA-based medicines that insert a healthy gene into cells to replace those missing or mutated) was first discussed in the early 1970s, it is still not widely known or understood. During the intervening decades there have been ups and downs in interest and it was not until 2003 that the first treatment was approved. This was in China, with a product called Gendicine for head and neck cancer. In the Western World, the first approval was not until Glybera by the EMA in 2012 (subsequently removed by the manufacturers). It took even longer for the first US approval of Kymriah for acute lymphoblastic leukemia in 2017 and to date there are only a handful more approvals. Potential applications are in treatment of diseases caused by recessive gene disorders (cystic fibrosis, MD etc), certain viral infections such as AIDS, and cancer. More recently retinal gene therapy has generated positive international news too. Could it be that after half a century the vision of genetic medicine is becoming more of a reality?