RARE Daily

PharmaTher Enters Option Agreement with CWRU to Develop and Commercialize Ketamine for Rett Syndrome

November 2, 2022

Rare Daily Staff

Canadian specialty pharmaceutical PharmaTher Holdings has entered into an evaluation and exclusive option agreement with Case Western Reserve University (CWRU) in the development and commercialization for the intellectual property of ketamine in the treatment of the rare neurological disorder 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,” said Fabio Chianelli, CEO of PharmaTher. “In research, ketamine has shown the potential for treating Rett syndrome. 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.”

Rett syndrome is a rare genetic neurological disorder that occurs almost exclusively in girls. It leads to severe impairments in their ability to speak, walk, eat, and even breathe easily. Prominent features of Rett syndrome include near constant repetitive hand movements and loss of purposeful hand use. Rett syndrome is usually recognized in children between 6 to 18 months. Rett syndrome is caused by mutations on the X chromosome on a gene called MECP2. Rett syndrome occurs worldwide in 1 of every 10,000 female births, and is much rarer in boys. Currently, there is no known cure or FDA-approved drugs for treating Rett syndrome.

Ketamine’s potential to treat Rett syndrome has been independently validated in two different laboratories in two different strains of Mecp2 mice and has completed a phase 2 clinical trial with Rett syndrome patients, with results not yet published. The therapeutic potential of ketamine for treating Rett syndrome was first demonstrated by David Katz, professor emeritus, Department of Neurosciences, School of Medicine at CWRU, and colleagues, who found that treatment of heterozygous female Mecp2 mutant mice with a subanesthetic dose of ketamine (8 mg/kg) acutely reversed abnormalities in Fos expression and sensorimotor function.

Chronic administration of ketamine was also found to improve symptoms and extend lifespan in null male Mecp2 mutants. The ability of low-dose ketamine to improve function across a broad range of symptoms may be related to its ability to increase cortical network activity, possibly by selective inhibition of GABAergic interneurons, as well as to decrease synaptic excitability in brainstem networks important for respiratory and autonomic control. Thus, ketamine may be ideally suited to redress the imbalance between cortical and brainstem activity that characterizes the MeCP2-deficient brain.

Moreover, in addition to its acute effects on circuit function, work in other disease models has shown that ketamine also rapidly stimulates dendritic growth, BDNF levels, and expression of key synaptic proteins, at least in part through activation of mTOR signaling, which is deficient in Mecp2 mutants. These findings suggest 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.

Under the terms of their agreement, PharmaTher paid a one-time fee to gain an exclusive option for up to 12 months to evaluate the regulatory, clinical development, and commercialization plan for CWRU’s intellectual property portfolio. Should PharmTher elect to exercise its option, both the company and the university will negotiate a license agreement.

Photo: Fabio Chianelli, CEO of PharmaTher

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