Relief from Rett?

NEW YORK—A recent exploratory study suggests that a compound currently in clinical trials to treat Alzheimer’s disease has potential to treat Rett syndrome also. Anavex Life Sciences announced in February that its compound Anavex 2-73 produced positive data when tested in a mouse model of the rare neurodegenerative disease, which develops mainly in young girls. The experiment was sponsored by Rettsyndrome.org, a nonprofit that aims to accelerate the testing of compounds to treat Rett by funding studies in a Rett mouse model.

“Anavex heard about our Scout program, which helps drug companies study a compound’s potential for Rett sydrome at very low risk,” Steve Kaminsky, chief science officer of Rettsyndrome.org, tells DDNews. “They took a chance by giving the drug to our contract research organization, and it produced very positive results with a solid amount of clinical data.”

Previous clinical tests of Anavex 2-73 for Alzheimer’s produced an attractive safety profile along with positive cognitive, anti-anxiety and anti-seizure effects. Since Alzheimer’s and Rett sydrome share many of the same symptoms, including cognitive impairment, anxiety and seizures, it seemed possible that the drug might have similarly positive results in the rare disease.

“Coupled with the positive preclinical data on cognition, antianxiety and antiseizure data, we decided to explore Anavex 2-73 in Rett syndrome,” Christopher Missling, CEO of Anavex, tells DDNews. “Recent third-party publications also indicated a positive effect of Anavex 2-73’s main target, the sigma-1 receptor’s involvement in movement disorders.”

Rett syndrome is a non-inherited disease that mainly affects girls. The disease cannot be predicted, and it usually first appears between the ages of 6 and 18 months, at which point girls lose purposeful use of their hands, show distinctive hand movements and experience slowed brain and head growth, as well as problems with walking, seizures and intellectual disability.

There is currently no cure for Rett. Treatments are extremely limited, and are aimed at treating symptoms such as breathing irregularities and seizures. The disease is caused by mutations in the MECP2 gene, which occurs in roughly one in every 10,000 to 15,000 live births, according to the National Institute of Neurological Disorders and Stroke.

“Given the strong clinical safety data profile of Anavex 2-73, it would be encouraging to explore the compound in patients with Rett syndrome, which is a very vulnerable patient population that, in addition to its neurodevelopmental symptoms, also experiences a significant number of seizures,” said Alan Percy, leader of the Rett syndrome Natural History Study, in a press statement.

The exploratory study of Anavex 2-73 in a mouse model that mimics Rett found that the compound produced significant improvements in tests measuring movement, behavioral factors and gait. The study involved chronic oral daily dosing that started at roughly 5.5 weeks of age over a 12-week behavioral testing time. Behavioral paradigms measured different aspects of muscular coordination, balance, motor learning and muscular strengths, which are some of the core deficits observed in Rett.

Missling says that Anavex is currently considering whether it will follow up on the positive findings with clinical studies.

“We are fortunate to have the chief scientific officer of the Epilepsy Foundation, Dr. Jacqueline French, on our scientific advisory board, in addition to having the support of Rettsyndrome.org,” comments Missling. “With their guidance, we are exploring the potential to advance Anavex 2-73 into human clinical studies for Rett syndrome.”

Anavex is also pursuing opportunities to test the potential of Anavex 2-73 to treat other diseases beyond Rett. The Michael J. Fox Foundation for Parkinson’s Research has awarded Anavex a research grant to develop the drug for the treatment of Parkinson’s disease to fully fund a preclinical study, which could justify moving it into a Parkinson’s disease clinical trial.

“The upstream mechanism of action of Anavex 2-73 with the potential to target not only neurodegenerative diseases such as Alzheimer’s, but also neurodevelopmental rare diseases like Rett syndrome, might indicate its potential to treat additional CNS disorders,” says Missling.