When Lucia received her diagnosis of WOREE Syndrome just before her first birthday, her parents were told there was no treatment or hope for improvement. For Johann, Lucia’s father, accepting this prognosis was impossible. Driven by determination, he embarked on a journey into the complex world of molecular biology.
WOREE Syndrome is an exceptionally rare genetic condition caused by mutations in the WWOX gene. In Lucia’s case, a nonsense mutation on one gene and a deletion on the other gene created a loss-of-function scenario, leaving her her without a critical protein for development and function, and her physicians and parents with limited options. Johann’s deep dive into medical research led him to learn about compounds that could potentially address nonsense mutations by promoting “readthrough” of faulty genetic instructions. However, early candidates, such as aminoglycosides like gentamicin, posed significant toxicity risks, making them unsuitable.
Discovering Amlexanox
Through exhaustive research, Johann came across a drug called amlexanox, a Japanese treatment previously used for asthma. Amlexanox stood out not only because it could potentially bypass nonsense mutations but also because it inhibited nonsense-mediated decay (NMD), a process that destroys incomplete proteins. Unlike other drugs Johann had investigated, amlexanox could cross the blood-brain barrier—a critical factor for treating neurological symptoms.
With careful persuasion, Johann convinced Lucia’s neurologist to try the treatment. The results were astounding. Within weeks of starting amlexanox, Lucia began achieving developmental milestones previously thought impossible—moving her legs, becoming more interactive, and vocalizing for the first time. For four months, her progress continued, bringing new hope to her family.
An Unexpected Challenge
Despite these promising results, their journey took a devastating turn when the sole manufacturer, Takeda Pharmaceuticals, discontinued amlexanox production. Johann exhausted every avenue to source the drug, from engaging researchers in Sydney to validate its effects on Lucia’s cells to sending someone to search pharmacies across Japan. All efforts failed. When Lucia’s treatment stopped, she regressed, erasing the remarkable gains she had made.
This heartbreaking setback highlighted the urgency of re-establishing access to amlexanox, not just for Lucia but for others living with rare genetic conditions. Johann’s story has since inspired biotech leader and social entrepreneur, Dr. Bruce Bloom, to establish a public-benefit corporation, Fortuity Pharma. This pharmaceutical company is bringing amlexanox back to the market, to potentially benefit Lucia and many more rare disease patients.
The Road Ahead
Lucia’s story underscores the immense challenges and opportunities in rare disease research. While existing treatments for nonsense mutations remain limited, the experience with amlexanox reveals untapped potential in re-examining off-patent drugs for new applications. Johann’s relentless advocacy has not only reignited interest in amlexanox but also drawn attention to the broader need for innovation in treating genetic disorders caused by nonsense mutations.
Lucia’s journey is a testament to the power of love, determination, and science to rewrite what is possible. It serves as a beacon of hope for other families navigating the uncertainties of rare diseases.
