A New Zealand patient has made medical history by becoming the first person worldwide to receive a groundbreaking gene therapy designed to treat facioscapulohumeral muscular dystrophy (FSHD), a rare hereditary disorder affecting approximately 130 people in New Zealand.
The experimental treatment, called ARO-DUX4 and developed by genetic therapeutics company Arrowhead, works by "silencing" the DUX4 gene that causes the debilitating muscle weakness characteristic of FSHD. The condition typically begins in childhood and primarily affects muscles in the face, shoulders, and upper arms.
Revolutionary Gene Silencing Approach
"What we're attempting to do is the job which the body is supposed to be doing by trying to suppress the expression of the DUX4 gene," explained Associate Professor Richard Roxburgh, the trial's principal investigator from the University of Auckland. The DUX4 gene expression causes significant damage in the bodies of people with FSHD, and this therapy targets muscle cells to prevent that harmful expression.
Roxburgh compared the significance of this first patient to "the first person to go to the moon," emphasizing the pioneering nature of the treatment. "Because it is a genetic treatment, it is only possible to test the drug on someone who has that particular genetic disorder," he noted.
Trial Design and Safety Protocol
The phase 1 trial follows a careful dose-escalation protocol involving 16 patients who will receive either a single low dose of ARO-DUX4 or a placebo. The study is structured with four groups of four patients each, testing progressively higher doses while ensuring safety at each level before advancing to the next dose.
Participants will be monitored for 90 days for adverse events. If no concerning reactions occur, researchers plan to launch a larger, year-long randomized controlled trial based in New Zealand, with additional international sites joining the study. These patients would be monitored for 360 days, followed by further trials to determine the optimal safe dosage.
Promising Results from Parallel Gene Therapy Trial
Concurrent with the FSHD trial, the University of Auckland is leading another pioneering gene therapy study for myotonic dystrophy, a more common neuromuscular disease affecting approximately 300 New Zealanders. This trial, testing a genetic therapy from Dyne Therapeutics, has produced encouraging early results from the first six months.
"It looks like it is really working and doing what we had hoped for," Roxburgh reported. "The patients are stronger and, most importantly, the underlying disease mechanism is being corrected, and the higher the dose, the more it is being corrected."
The positive outcomes have prompted the drug company to begin planning for a final, larger trial with the goal of bringing the therapy to market within the next few years.
New Zealand's Strategic Advantage in Rare Disease Research
New Zealand's position as the global leader in launching these trials stems from several key advantages, including the New Zealand Neurogenetic Registry and Biobank (Punaha Io), which facilitates patient contact and recruitment even for rare neurogenetic diseases. The University of Auckland's strong connections with patient advocacy groups and research partners at Te Toka Tumai Auckland Hospital and New Zealand Clinical Research centre further enhance the country's research capabilities.
"These therapies are treating genetic disorders that have a huge impact on people's lives," Roxburgh observed. "They don't get the attention the likes of cancer therapies get, possibly because of the small numbers of people involved. But for these patients, the treatments are life-changing."
Transformative Potential of Genetic Therapies
The University of Auckland is set to join another genetic therapy trial this year with Avidity, which is in the final stages before seeking FDA approval for market authorization. These developments represent part of a broader transformation in genetic disease treatment enabled by worldwide research and technology advances.
"It's exciting, because the therapies target the specific gene that is causing the disease, which is why we get so few off-target effects," Roxburgh explained. He emphasized the revolutionary nature of these treatments, stating, "It's as significant as having antibiotics versus not having antibiotics."
Roxburgh acknowledged the courage required of trial participants, noting that "they really are brave in taking on the study, but they already have to face decisions that others without the disease don't have to make, on a daily basis." The results from the myotonic dystrophy trial will be presented at the International Congress of Neuromuscular Diseases in October 2024, where thousands of researchers from around the world will gather to hear the findings.
