Can a Pharma Drug Improve Autism Conditions?

According to the U.S. Centers for Disease Control and Prevention (CDC), about one in 59 babies born in the United States has been identified with autism spectrum disorder. Since 2000, the prevalence of autism in U.S. children has increased by nearly 120 percent, making it the fastest growing developmental disability in the country.

There are no treatments for autism, but that’s not stopping research into the development of therapies for core symptoms of autism spectrum disorder. This week, London-based AMO Pharma reported Phase II results from its investigational glycogen synthase kinase 3 (GSK3) beta inhibitor, AMO-02 (tideglusib), which showed patients dosed with the medication during the trial experienced an improvement in social withdrawal, repetitive behaviors, daily living skills, memory and sleep quality.

Privately-held AMO Pharma said that preclinical studies indicate that GSK3 beta is an enzyme that is overactive in key molecular pathways that are germane to neuronal functioning and neuronal plasticity in neurodevelopmental disorders. GSK3 beta plays an important role in circadian function and in modulating neuroinflammatory processes in the brain. In patients battling neuromuscular diseases, such as congenital myotonic dystrophy and even Duchenne muscular dystrophy, activity of glycogen synthase kinase 3 beta (GSK3ß) has been shown to increase.

The Phase II trial was a 1:1 double-blind study. Patients were treated with either AMO-02 or placebo over a 12 week period. Patients treated with AMO-02 consistently outperformed placebo in measures of social withdrawal and repetitive behaviors), as well as daily living skills, memory and sleep quality, AMO said in a statement. Outcome measures were based on measures including caregiver-and clinician-completed rating scales. A permutation test of efficacy results indicated that probability of false-positives was low, AMO Pharma added. The once-daily treatment for the core symptoms of ASD was found generally safe and well-tolerated, the company said.

Michael Snape, chief executive officer of AMO, said the Phase II TIDE study marks the first time that a GSK3 beta inhibitor has been the focus of a clinical trial for autism spectrum disorder.

“We believe the resulting data represent a positive step forward in validation of GSK3β as a molecular target in the treatment of symptoms associated with ASD beyond any existing published pre-clinical data,” Snape said in a statement.

Autism is known as a “spectrum” disorder because there is wide variation in the type and severity of symptoms people experience.

Joseph Horrigan, AMO’s chief medical officer said that over the past 10 years, there has been little progress in research related to autism spectrum disorder, all while the “incidence of ASD seemingly continues to rise.” The results of the Phase II TIDE trial provide a new level of hope for potential treatment to the conditions of ASD, Horrigan said.

“…treatment with AMO-02 has the potential to offer meaningful, multi-symptom benefit in ASD and merits further study as a potential treatment for ASD,” Horrigan said.

In addition to ASD, AMO is also investigating AMO-02 for the treatment for onset myotonic dystrophy type 1. Earlier this year, the company reported Phase II data that showed AMO-02 demonstrated clinical benefits in those patients, such as an improvement in cognitive function and an increased ability to perform daily tasks. Myotonic dystrophy type 1 is a rare, genetic, life-threatening neuromuscular disorder that causes impairment in muscle function, cognition and quality of life.

In July 2017 the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for AMO-02. The designation is granted to developmental treatments for rare diseases/disorders that affect fewer than 200,000 people in the U.S.