Amlexanox is a fascinating drug that has had a unique journey in the medical field, evolving from a treatment for asthma to mouth ulcers to a potential therapy for chronic diseases like diabetes, obesity and rare genetic conditions. Here’s a look at its history and how this small molecule has gained interest for various uses.
The Discovery and Chemical Nature of Amlexanox
Amlexanox was first developed by the Japanese pharmaceutical company Takeda Pharmaceuticals. Its molecular structure is characterized as a unique pyridine carboxylic acid derivative, which grants it anti-inflammatory, anti-allergic, and immunomodulatory properties. These attributes made it an intriguing candidate for treating conditions involving immune system dysregulation, such as allergies and autoimmune diseases.
Amlexanox functions primarily by inhibiting inflammatory mediators like histamine and leukotrienes, substances that play a key role in allergic and inflammatory responses. Its ability to modulate these pathways laid the foundation for its initial clinical applications.
Early Applications: Allergies and Inflammation
Amlexanox was first approved in Japan, under the trade name Solfa, during the 1980s for the treatment of allergic conditions, including asthma and rhinitis. By the 1990s, it gained additional approvals in other countries, including the U.S. where the Food and Drug Administration (FDA) approved amlexanox, under the brand name Aphthasol, as a topical treatment for treating canker sores (aphthous ulcers). Its localized application as an oral paste provided relief for millions.
Reemergence in Metabolic Disease Research
After its initial success, researchers began exploring whether amlexanox could be used for other conditions. The drug’s ability to affect inflammation made it a candidate for chronic diseases where the body’s immune response is out of control.
In 2013, a groundbreaking study led by Dr. Alan Saltiel at the University of Michigan identified amlexanox as an inhibitor of two key enzymes: IKK-ε (I-kappa-B kinase epsilon) and TBK1 (TANK-binding kinase 1). These enzymes are implicated in the chronic inflammation associated with obesity and metabolic syndrome.
Preclinical trials in animal models revealed that amlexanox could improve insulin sensitivity, reduce fatty liver, and promote weight loss by targeting these pathways. These findings sparked renewed interest in repurposing amlexanox for human metabolic disorders, such as type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).
Uncovering a New Mechanism of Action for Rare Diseases
Another compelling chapter in amlexanox’s story is unfolding today. Rare disease researchers have found that it can target a cellular process called nonsense-mediated decay (NMD). This process often interferes with the production of essential proteins in people with genetic conditions caused by “nonsense mutations.” These mutations create faulty stop signals in DNA, preventing cells from making the proteins they need to function properly.
For patients with diseases like Charcot-Marie-Tooth disease and Duchenne Muscular Dystrophy, amlexanox has shown promise in preclinical studies. Early experiments suggest it may help restore the production of missing proteins, offering a potential breakthrough for conditions that currently have no effective treatments.
Challenges and the Path Ahead
Despite its potential, amlexanox faces significant hurdles. The drug manufacturing and marketing was discontinued in Japan in 2019, leaving patients and researchers without a steady supply. Fortuity Pharma, a mission-driven pharmaceutical company, has taken on the challenge of bringing the drug back to market. Founded by Dr. Bruce Bloom, the company is focusing on using amlexanox to treat rare diseases.
Fortuity Pharma plans to conduct observational studies and clinical trials to prove the drug’s effectiveness in treating conditions caused by nonsense mutations. By repurposing this “old” drug for new uses, they hope to make a significant impact on the lives of patients and families in the rare disease community.
Amlexanox’s story is a testament to the power of scientific curiosity and patient advocacy. From its beginnings as a niche treatment in the US for canker sores to potentially addressing some of the most challenging chronic diseases, this drug exemplifies how innovation can breathe new life into forgotten therapies if it can be proven to help these rare diseases.
With organizations like Fortuity Pharma leading the charge, amlexanox could soon play a pivotal role in rare disease treatment, offering hope to countless patients worldwide.
