Reaching for the stars

Many of us would like to be a bit taller, but for some children it would be life-changing.

A world-first treatment, developed from MCRI-led research, is allowing those with achondroplasia to grow at the same rate as their peers and possibly avoid surgery.

Achondroplasia is caused by a gene mutation affecting about one in 25,000 babies. Until recently there was no treatment. Children with the condition have impaired bone growth in the limbs, spine, and base of the skull. They may also have curvature of the spinal cord, bowed legs and spinal cord compression. About half need corrective surgery.

MCRI clinical geneticist Professor Ravi Savarirayan has spent almost 10 years working to counter the inhibited growth and other complications.

A ray of hope emerged in 2011, when he learned that scientists had found that a small molecule dubbed CNP was an important bone growth regulator and blocked the pathway responsible for achondroplasia.

Successful trials

As a result, the drug vosoritide was developed to improve bone growth in children with the condition.

Since Ravi treated his first human patient in 2013, he has led several successful trials of the drug.

He says the results of these and other studies are extremely promising. "If it works as hoped, vosoritide could help children with achondroplasia grow taller and avoid surgery," he says.

"This could be life-changing for many children and their families."

The Phase 2 study of children aged five to 14 found those who took higher doses grew faster for up to 42 months. Importantly, vosoritide was generally well-tolerated.

These ground-breaking findings were reported in the prestigious New England Journal of Medicine.

Bike rides and running races

For children successfully treated with vorsoritide, growing at the same rate as other kids their age makes a world of difference.

The primary goal of the trial was to stop the significant medical complications that can come with achondroplasia and avoid complicated major surgery, but many children and families saw some added benefits.

For some children, the extra height meant being able to reach the pedals on a bicycle for the first time. Families and teachers reported that the children were better able to keep up with friends in the playground.

Ravi says achondroplasia is caused by overactivity of a signal that stops growth, and could be likened to overwatering a plant.

"Basically vorsoritide kinks the hose so that the plant gets the right amount of water and can resume regular growth," he says.

Now, Ravi's guidelines for managing achondroplasia in children have been adopted into the practice guidelines at The Royal Children's Hospital in Melbourne and dozens more hospitals around the world.

A united approach

This research is a prime example of MCRI's work with the Melbourne Children's Trial Centre (MCTC), a unique collaboration between The Royal Children's Hospital, MCRI, The Royal Children's Hospital Foundation and The University of Melbourne.

MCTC, led by Professor Andrew Davidson, supports clinicians and researchers to initiate and perform trials of new therapies, like the one for vosoritide. Clinical trials are essential to explore the effectiveness of promising new therapies, and to determine how existing treatments can be used most effectively.

The unique collaboration with MCTC takes research from 'bench to bedside'.

A leader in paediatric trial design, MCTC runs a range of clinical trials and has staff to support each stage from concept to protocol design, trial conduct and analysis. It collaborates with other research institutes, universities and industry leaders across a range of complex projects.

"Trials like the Phase 2 vosoritide project, which ran across Australia, the UK, France and the USA, would not be possible without these links," Ravi says.

Professor Andrew Davidson, Medical Director of MCTC, says: "The Melbourne Children's Trial Centre gives MCRI and the Melbourne Children's campus a unique capacity to trial our research in a way that has great benefit for researchers and clinicians as well as patients and families."