Guest blog post by Gael Gordon PhD.

This week for the first time, I appeared in the Sun.  I would like to make it clear that this was never on my bucket-list but getting the news about Rett Syndrome sometimes means doing stuff like this.  The newspaper had picked up on a concert that my brother, Colin, was holding to raise money for Reverse Rett. Speaking to the journalist, and not being media trained, I happened to mention that my daughter, Romi, has been doing better since being treated with Ketamine. So instead of a story about a charity concert, the journalist ran with a rather different story.

You may be familiar with Ketamine either as a horse-tranquilizer or a drug of abuse but it’s also - occasionally - used in human medicine, mainly as general anaesthetic. Very, very occasionally, it is used as a treatment for non-convulsive status in children (this is an epileptic event where non-convulsive seizures, such as absences, continue for hours or days.) There is some anecdotal evidence that girls with Rett syndrome can show a mild reduction in their symtoms for a couple of days after having ketamine as a general anaesthetic. There is also evidence that mice with Rett syndrome in the lab benefit from treatment with Ketamine. The scientists speculate that Ketamine triggers changes within the brain in Rett Syndrome. Incredibly, these changes may persist even after the drug has been withdrawn. A drug like Ketamine has some advantages over other novel therapies. It’s an old drug, which means it is cheap and it has already been cleared for use in humans. Importantly, because it is a drug of abuse, doctors also have a very good idea of the safety profile of the drug – at least in adults - and its unwanted side effects have been well documented.

My daughter, Romi, has the R133C variant of Rett Syndrome.This genetic mutation generally leads to a milder form of the disorder. While Romi has lost the ability to speak and use her hands, she has always retained the ability to walk. Romi has, however, very difficult-to-treat epilepsy. This has led to many, many hospital admissions. Indeed, things were so bad that in 2015 Romi spent as much time in hospital as at home.  It reached the point where I considered epilepsy, not Rett Syndrome, to be Romi’s primary diagnosis.

In February 2016, Romi was admitted to hospital again. We had run out of options at home. After a relentless week of seizures following the admission, the on-call neurologist admitted that he was starting to run out of options too. The difficulty is that Romi, like many girls with Rett, is sensitive to a lot of drugs. Many of the first-line medicines that can be used to stop seizures also affect Romi’s breathing. 

We are very lucky where we live.  Romi’s care is delivered by a world class team of tertiary care epilepsy specialists who are active researchers in the field.  Romi’s team were aware of a clinical trial of Ketamine in girls with Rett Syndrome being run by Professor Katz in the USA (http://www.reverserett.org.uk/news/research-made-easy-ketamine-clinical-trial).  With the trial at the back of their minds (but with no real expectation that the Ketamine would help the symptoms of Rett), Romi was started on a very, very low-dose of the drug for five days in an attempt to break the seizure cycle. On day 1, she slept. After that sleepy first day, she was much more alert and the seizures reduced. On day 6, following the withdrawal of the drug, she had several more seizures. Then she woke up.

This is not the first time that we have seen an “awakening” in Romi with new drugs and this at first seemed similar. Romi became hyper-alert and hyper-sensitive (to noise and to light) on the ward. Then her hands started to free up. She started walking with her hands swinging from her sides (when normally they were always clasped together). She said 'bye-bye'(I cried) and then waved when I related this to the doctor (everybody cried). She started to nod (occasionally) and shake her head (more frequently) for yes and no (she hasn’t been able to do this since she was a toddler.) She started to use her index finger more, which allowed her to point independently at symbols in her communication book. Her seizures became more manageable. Unlike the other 'awakenings', however, after more than a year, Romi is still doing well.

Romi had two further five-day courses of ketamine following two further admissions (in April 2016 and April 2017).  After each there was a slight improvement in her symptoms.  Incredibly, following her most recent course, she said a few more words: “Mummy” and “Daddy” (and “Pizza”!). Romi’s not been cured. People who don't know Romi will still see a very disabled child. People who know her well, however, all comment on the change. To us, her family, it feels like a small miracle.

Was it the Ketamine? Perhaps. It’s possible that the ketamine has reduced the hyper-excitability of the neural cells in her brain, leading to a reduction in seizures, which in turn has improved Romi’s brain function. It may be that the Ketamine has led to persistent changes in Romi’s brain improving her movement control and the reduction in seizures is a side-effect of these changes. Perhaps it’s only a coincidence. Would further treatment lead to further improvements?  Is there something particular about Romi or would other children benefit in the same way? Who knows? The only way to answer these questions is with good quality research studies......and that’s where Reverse Rett comes in.

Since 2013, Reverse Rett has contributed over $210,000 to pre-clinical work on Ketamine funded by the Rett Syndrome Research Trust.

Here is a link to further information about the current Ketamine clinical trial which is taking place at the Cleveland Clinic in Ohio.

If you would like to receive information about current or future UK clinical trials, please register your child or adult with Rett Syndrome on the Reverse Rett Patient Registry here.