University, PharmaTher Join Forces to Develop Ketamine for Rett

Ketamine shown in preclinical studies to reverse Rett-related abnormalities

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

Share this article:

Share article via email
An illustration shows two people shaking hands.

Case Western Reserve University (CWRU) is partnering with PharmaTher to develop and commercialize ketamine for the treatment of Rett Syndrome.

“We are pleased to have added the Rett syndrome program to our clinical-stage product pipeline that focuses on novel uses and delivery forms of ketamine in the treatment of mental health, neurological and pain disorders,” Fabio Chianelli, PharmaTher’s CEO, said in a company press release.

Recommended Reading
Rett syndrome diagnosis | Rett Syndrome News | announcement illustration of woman with megaphone

Analyzing Babies’ Vocalizations May Help in Early Detection of Rett

Ketamine gives users feeling of detachment from surroundings

Ketamine is a dissociative anesthetic — a hallucinogenic compound that provides users with a feeling of detachment from their surroundings. It was approved as an anesthetic by the U.S. Food and Drug Administration (FDA) in 1970, and a ketamine-derived medicine called esketamine is currently approved for depression.

The potential of ketamine as a Rett syndrome therapy was first demonstrated in a mouse model of the disease by researchers at CWRU under the leadership of David M. Katz, PhD, professor emeritus at the school of medicine.

A low, sub-anesthetic dose of ketamine (8 mg/kg) was shown to acutely reverse Rett-related abnormalities in female mice with Rett-like disease.

Further preclinical research suggested that “in addition to acute rescue of neurological function, ketamine also has the potential to promote synaptic repair in Rett syndrome by enhancing structural and functional connectivity, as previously shown in animal models of depression and stress,” PharmaTher stated in the release. Synapses are the sites where nerve cells communicate.

In research, ketamine has shown the potential for treating Rett syndrome

Phase 2 trial tested ketamine in 24 girls with Rett

A first exploratory Phase 1 clinical trial (NCT02562820) testing ketamine treatment for Rett syndrome was terminated due to funding withdrawal.

In 2019, the Rett Syndrome Research Trust, in collaboration with the Vanderbilt University Medical Center, launched the now-completed Phase 2 trial (NCT03633058) to evaluate the safety and efficacy of ketamine in girls with Rett, ages 6–13 years.

A total of 24 girls were enrolled at several U.S. sites. Participants were randomly assigned to receive, in random order, a five-day treatment with one of two doses of ketamine (0.75 or 1.5 mg/kg) and a five-day regimen with a placebo. Both ketamine and a placebo were taken twice daily.

Changes in motor function, behavior, sleep habits, and brain electrical activity were assessed over two weeks after each regimen, as well as adverse events (side effects). Trial data have yet to be released.

Phase 2 trial results and other unpublished data will be evaluated to support a defined clinical and regulatory strategy for FDA feedback, according to PharmaTher.

“In research, ketamine has shown the potential for treating Rett syndrome,” Chianelli said. “We will work with CWRU and the clinical trial team in pursuing discussions with the FDA to determine all regulatory and clinical options that could expedite the pathway towards having ketamine available for Rett syndrome patients.”

Under the terms of the agreement, PharmaTher gained an exclusive option for up to one year to evaluate the regulatory, clinical development, and commercialization plans for ketamine. CWRU’s ketamine intellectual property portfolio includes one U.S. patent and two U.S. provisional patents.

PharmaTher paid a one-time fee to enter the partnership, and should it choose to exercise its option, both CWRU and the company will negotiate a licensing agreement.