Strong Voices

New Zealand families are celebrating the release of the first drug to treat the severe neurological condition Rett syndrome and wondering if they will see it here.

The drug, Trofinetide, has been approved by the United States Food and Drug Administration. It went on the market in April.

Rett syndrome is a rare genetic condition that occurs almost exclusively in girls, affecting their ability to speak, walk, eat and breathe easily. It is characterised by constant repetitive hand movements.

Rett syndrome is caused by errors in the MECP2 gene, which inhibit the formation of a molecule essential to cognitive and motor function. Movement and communication skills stagnate or regress after the first six to 18 months of a child’s life.

Rett families in New Zealand have a special connection to the drug. The molecule that led to its development was created here 20 years ago at the University of Auckland by a small team of chemists led by Distinguished Professor Dame Margaret Brimble.

Dame Margaret was working with three chemists, David Callis, Nick Trotter and Paul Harris and alongside biologists Associate Professor Jian Guan and Professor Mike Dragunow. They had been looking for a treatment for brain injury.

Their synthetic molecule didn’t work for brain injuries, but scientists working for University of Auckland company Neuren Pharmaceuticals investigated its potential to treat Rett syndrome and it eventually became the basis for Trofinetide. Neuren took the drug into phase two clinical trials and then partnered with US company Acadia Pharmaceuticals to carry out phase three trials.

Successes in clinical trials have included girls walking or talking for the first time. Acadia is marketing Trofinetide in the US as Daybue.

“We obviously have been awaiting the outcome of trials and we are very pleased it’s on the market,” says Rett New Zealand Trust Chair Dugald MacBrayne. “But we are still quite a bit in the dark about what it will do. If and when it becomes available, then we will certainly put our hands up.”

Dugald and Christine’s daughter Mandy is 40 and has Rett. They are not sure what the drug might mean for her.“Mandy has never spoken – we had a couple of words out of her. What we would wish for is a better level of response,” Dugald says. “Mandy understands a great deal of what we say but cannot respond to us.”

The drug will likely undergo trials in Europe and in Australia before being assessed by Pharmac here. Dugald says the biggest obstacle to Pharmac funding is the small number of people here likely to benefit.

In an interview with University of Auckland’s UniNews magazine, Dame Margaret said she was hoping the drug would get Pharmac approval to enable New Zealanders to be treated.

“While there might only be around 40 to 60 Rett patients in New Zealand, this drug was painstakingly developed over many years by many New Zealanders and a New Zealand company, Neuren Pharmaceuticals, which started here at the University of Auckland, so I’d really hope it can be used in this country. “Obviously, having created the key molecule, I’ve followed its progress into clinical trials closely and understood the importance for Rett syndrome patients,” says Dame Margaret.

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Caption: Mandy MacBrayne shares a smile with her mum, Christine. Christine and Dugald MacBrayne hope that the new Rett drug will mean Mandy can communicate more easily.

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