Emily and Mitch still remember the afternoon they received a phone call informing them their newborn baby boy had screened positive for Spinal Muscular Atrophy (SMA).

The rare genetic disease causes progressive muscle weakness from the degeneration of motor neurons in the spinal cord. For babies born with severe types of SMA, a diagnosis often meant they would never gain the ability to sit or even live to their first birthday.

"We had Mitch's family over to see Xavier at home for the first time when I took the phone call. It was from a neurologist at the Sydney Children’s Hospital, and they told us Xavier’s newborn screening was positive for SMA."

"It left us completely numb and confused," Xavier’s mum, Emily, said.

At the time treatment options for SMA were very limited. Just a few years prior, none even existed.

Emily and Mitch were presented with two treatment options for Xavier—a drug that needed to be administered via an injection in Xavier’s spinal fluid multiple times a year for the rest of his life, or a new trial medication administered orally once a day.

"We were honestly torn and didn't know what to choose for Xavier. The hospital team were so supportive and knowledgeable, and with the help of our family, we decided we wanted Xavier to be on the trial."

The clinical trial Xavier enrolled in was dubbed the RAINBOWFISH trial and was testing an oral medication, risdiplam, in a cohort of 26 presymptomatic infants with SMA over two years.

Risdiplam helps the body produce more of an essential protein that is deficient in SMA, known as Survival Motor Neuron (SMN) protein. It does this by targeting the RNA encoded by the SMN2 gene, which is almost identical to the altered SMN1 gene that causes SMA, enabling it to produce functional SMN protein.

Neurologist, Professor Michelle Farrar, at the Sydney Children’s Hospital, Randwick, and UNSW Sydney, co-led the international study with colleagues from around the world in the United States, Belgium, Brazil, Poland, Russia and Taiwan.

"The really exciting thing about this is that it's an oral drug which can be taken at home and be initiated as soon as the diagnosis is made. It is important to start treatment as soon as possible to preserve strength from the very start."

"Every day counts when there is irreversible loss of motor neurons," Prof Farrar said.

By the end of the two-year trial period, the results were dramatic, with the participants reaching milestones that untreated children with SMA would not achieve. Of the 26 children, 25 could sit unsupported at twelve months, and 21 were walking alone at two years.

Xavier is five years old now, attending preschool and swimming lessons like most children his age. He can walk independently, climb and dance. Every day he shows off his cheeky personality to his family, playing, laughing, and joking around with his brother and friends.

"He is confident and determined and will always try to do new things, or try to achieve what he wants in a brave way," Emily said.

"For example, we had a planning meeting with Xavier’s preschool to see how to make their cubby house accessible for him, because it was up on a tall metal ladder—which we thought would not be possible for Xavier to access. Little did we all know that it only took Xavier a week to successfully climb that ladder independently. At the top of the ladder, he yelled to his teachers with a huge smile on his face. They were in shock."

The RAINBOWFISH study was published in the prestigious New England Journal of Medicine, and builds on the momentum of other SMA research studies over the last few years, offering hope for the thousands of families impacted around the world.

"SMA is not solved," Prof Farrar stresses. "The story is not over. We continue to look at how we can optimise outcomes through therapies and understanding the disease."

With around 30% of study participants in the trial being at the Sydney Children’s Hospital, Randwick, the Sydney Children’s Hospitals Network continues to integrate world-leading clinical research into healthcare, driving innovation and accelerating access to novel, potentially life-changing treatments children and young people.

Professor Farrar leads the Paediatric Neurology Research Group, an affiliated group with UNSW, part of Kids Research. The clinical trial was operated through the Kids Neuro Trials team based at the Sydney Children’s Hospital, Randwick.