Gene therapy gives families hope for babies with spinal muscular atrophy

A trial has revealed that babies with SMA treated with gene therapy are meeting the normal developmental milestones of any baby.

Research conducted at Sydney Children's Hospitals Network (SCHN), with support from UNSW Sydney and Luminesce Alliance, has found that gene therapy may provide an effective treatment for spinal muscular atrophy (SMA) – a devastating and fatal genetic condition that causes progressive muscle weakness in babies, preventing them from being able to roll, sit up, crawl, walk and eventually breathe. Until recently, it was the leading genetic cause of infant death in Australia, occurring in one in every 10,000 births.

Results from the first part of the SPR1NT trial were presented last week at the European Academy of Neurology (EAN) Conference. This trial investigated the use of Zolgensma, a novel viral vector-based gene replacement therapy. Fourteen infants, who were under six weeks of age and at risk of developing the most common and severe form of SMA, were treated before their symptoms started.

Study lead, Associate Professor Michelle Farrar, UNSW and Paediatric Neurologist at Sydney Children's Hospital, Randwick, said the results of the trial were a potential game-changer for both clinicians and families affected by SMA.

“These results are extremely exciting and encouraging, not only are these children surviving but with this therapy, most are meeting the developmental milestones of any normal baby, which is unheard of,” A/Prof. Farrar said.

Sydney Children’s Hospitals Network (SCHN) was the only Australian site selected to participate in the trial, and was one of the largest global recruitment sites, with four patients enrolled from SCHN. The recent introduction of SMA testing to the newborn screening program in NSW funded by a $2 million investment from the NSW government, made this possible.

The study, which followed each participant until aged 18 months, found that all children achieved the ability to sit independently (with 78 per cent achieving this milestone within the normal developmental window), all were alive and free of permanent ventilation, and all had normal swallow function and were fed exclusively by mouth by 18 months of age.

The trial also showed that following treatment, nine children were able to walk independently, and all showed fine motor performance similar to babies without SMA by the completion of the study.

'Early results suggest we may have been able to take what was considered a lethal disease, and turn that around.'

Zolgensma works by treating SMA at its root cause, inserting a functioning copy of the defective gene into the cells.

“By identifying these infants with SMA before the onset of symptoms, early results suggest we may have been able to take what was considered a lethal disease, and turn that around with a one-time, single-dose infusion,” A/Prof. Farrar said.

“It is giving life back to these babies and hope back to their families.”

Since the introduction of SMA into the newborn screening program in 2018, more than 200,000 babies have been screened, which has helped significantly with early identification of the condition.

“We know that early identification is vital in the treatment of SMA and that is what the newborn screening program has allowed us to do. It has radically shifted our model of care and we are now in a position where we can rewrite the history of SMA,” said A/Prof Farrar.

In addition to the newborn screening program, the NSW government has invested $25 million to boost the state’s capability to manufacture viral vectors – the key components of this type of therapy, which holds great promise for novel treatments for other genetic diseases.

The second part of the SPR1NT trial, which explored the effect of Zolgensma in babies with milder SMA, is due to be presented later this year.