Ketamine Could Soon Be A Treatment Option For This Rare Genetic Neurological Disorder

Specialty biopharma company PharmaTher Holdings Ltd. PHRRF has entered into an evaluation and exclusive option agreement with Case Western Reserve University (CWRU) for the development and commercialization of the IP of ketamine for the treatment of the Rett Syndrome (RTS), a rare genetic neurological disorder that causes severe muscle movement disability.

Current FDA-approved drugs do not offer any cure for Rett syndrome. This rare disorder occurs almost exclusively in girls and leads to severe impairments in their ability to speak, walk, eat and even breathe.

Ketamine has been tested for this syndrome in a Phase 2 clinical trial promising outcomes to support a defined clinical and regulatory plan for FDA feedback and the eventual development of lawful ketamine therapy for Rett syndrome.

PharmaTher’s CEO Fabio Chianelli said the company is pleased to have added the RTS program to its clinical-stage product pipeline developing novel uses and delivery systems of ketamine for mental health, neurological and pain disorders. 

The agreement’s terms give PharmaTher an exclusive option for up to 12 months to evaluate the regulatory, clinical development and commercialization plan for CWRU’s IP portfolio, including a US-issued patent and a provisional patent for composition and method for the treatment of pervasive developmental disorders, and US provisional patent for acute and sustained effects of low-dose ketamine treatment in mouse models of Rett Syndrome.

More About The Rett Syndrome

With prominent features including near-constant repetitive hand movements and loss of purposeful hand use, Rett syndrome is usually recognized in children between 6 to 18 months.

It is caused by mutations of the X chromosome on a gene called MECP2, occurring in 1 of every 10,000 female births worldwide. In the boys’ case, the number is much lower.

Ketamine’s potential to treat Rett syndrome has been independently validated in two laboratories in two different strains of MECP2 mice and has completed a Phase 2 clinical study though results have not been published yet. 

The drug’s therapeutic potential for treating this syndrome was first proved by Dr. David M. Katz, professor emeritus at the department of neurosciences in CWRU’s school of medicine and colleagues who found promising results of subanesthetic doses of ketamine on female MECP2 mutant mice in terms of acutely reversing abnormalities in Fos expression and sensorimotor function. 

While 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.

Ketamine then 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, deficient in MECP2 mutants. 

Together, 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.

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