Can Rett syndrome be reversed?

by Nancy Fliesler on December 21, 2010

Khwaja evaluates a young girl with Rett syndrome, the leading known genetic cause of autism in girls.

In 2007 an extraordinary paper was published, suggesting that developmental disorders, including autism spectrum disorders, aren’t necessarily a done deal. Working with a mouse model of Rett syndrome, a disorder causing severe cognitive, motor and language problems and autistic behaviors, mostly in girls, researchers in Scotland restored the function of MeCP2, the mutated gene. The mice showed a striking reversal of their neurologic symptoms.

The paper has had an impact around the world, changing how scientists think about disorders that have been thought to be untreatable. Typically, girls with Rett start developing normally, but sometime between age 1 and 2 they begin to lose their blooming language and motor skills. Until recently, Rett was viewed as a degenerative disease, with a gradual, irreversible loss of brain cells. “It was thought that if there ever was a treatment, it would have to be given before symptoms appeared, and that once the disease started it couldn’t be reversed,” says Omar Khwaja, a neurologist at Children’s Hospital Boston.

But in fact, research has shown that neurons aren’t lost. Instead, the synapses—the points of communication between brain cells—fail to mature, are unstable and are ultimately lost, impairing learning ability. And it appears these lost connections can be restored, at least in mice.

Last week, Khwaja and colleagues announced the opening of a randomized clinical trial, funded by the International Rett Syndrome Foundation, Autism Speaks and Harvard Catalyst. Forty girls with Rett syndrome, age 2 to 12, will receive insulin-like growth factor-1 (IGF-1), a human hormone used mainly to treat short stature. IGF-1 is indirectly regulated by MeCP2, and in the laboratory, it has been shown to enhance synapse maturation, and it has ameliorated several features of Rett-like disease in mice.

“There’s been a big sea change in how Rett syndrome and other neurodevelopmental disorders are viewed,” Khwaja says. “The synapses are very dynamic. They need to be stabilized, and if they don’t receive the right stimulus, they’ll naturally disappear. That change in paradigm has really affected the way that we look at treatments, and I think it brings a lot more hope.”

Rett syndrome is only the first of several neurodevelopmental disorders that appear amenable to change. As genetic disorders causing cognitive and autism-like impairments are becoming better understood, scientists are finding biochemical pathways that can be targeted by drugs. Tomorrow’s post will explore this trend in more detail.

30 comments

  • Mom of 2 boys

    My son has autism and what struck me about the article was the mention of the use of a growth hormone! When my son was 2, the Dr. predicted his adult height from his age 2 height. She said that we might want to give him growth hormone when he was a little older because he was only expected to be 5′ 4″. My son wasn’t diagnosed with autism until age 4. I will be watching to see what effects the growth hormone has on children with Rett syndrome.

    • http://www.facebook.com/muskegon Muskegon Michigan

      @46d11fc159da05c9b10c323e0caa4d8e:disqus Please be aware that “growth hormone” is NOT the same as “insulin-like growth factor (IGF-1)”. Although they have a lot to do with each other, they are indeed different and this acticle is about IGF-1.

  • Noreen_albright

    This is Such Great NEWS!!! I am so happy for all the families affected with this terrible syndrome.

  • Mom of 2 boys

    My son has autism and what struck me about the article was the mention of the use of a growth hormone! When my son was 2, the Dr. predicted his adult height from his age 2 height. She said that we might want to give him growth hormone when he was a little older because he was only expected to be 5' 4″. My son wasn't diagnosed with autism until age 4. I will be watching to see what effects the growth hormone has on children with Rett syndrome.

  • Noreen_albright

    This is Such Great NEWS!!! I am so happy for all the families affected with this terrible syndrome.

  • Marshall000222

    weird way of how reets works. she was sayin up to ten different words before the age of one, then right after that u can see the disease takes its toll. Her eye contact,language,communcation was all but gone. They now have her on medicine type of a blood pressure to try and slow her down because she likes to over stimulate. But that is a great progress of reets and hopefully it will be availalble for all children to help them!

  • Marshall000222

    weird way of how reets works. she was sayin up to ten different words before the age of one, then right after that u can see the disease takes its toll. Her eye contact,language,communcation was all but gone. They now have her on medicine type of a blood pressure to try and slow her down because she likes to over stimulate. But that is a great progress of reets and hopefully it will be availalble for all children to help them!

  • Anonymous

    My neice is participating in the clinical trial..we a re hoping for a miracle!
     

    • Alcionemichelon

      Hello, I would like to know if your neice has a results for the clinical trial???

      • Rebelle59

        She is in Phase I of the trial. Phase I is to make sure it is safe to give to the girls. So far so good. It seems to have improved her walking and also she doesnt seem to have as many stomach issues..keep praying!

    • Omdeadas

      Hi mate! u mentioned about your niece is participating in the trial. Can I ask you what is the latest with her regarding the trial. My 4yrs old daughter has rett. Im from the UK

    • Mn_aziz

      Please let me know how your neice is doing.  My daughter is diagnosed with this Rett Syndrome.  My email address is: mn_aziz@hotmail.com

  • Muna osman

    hi   Rebelle 59  
    how long will it takes to receive  results?  really am looking farward to help my daughter

    • Mn_aziz

      My daughter has rett syndrome too.  Please tell us what else you are doing about her symptoms.

  • Muna osman

    my daughter has Rett  syndrome   …..so how long  will it takes to receive the resulets

    • Nancy Fliesler (editor)

      The trial’s principal investigator, Omar Khwaja, MD, PhD, tells me that the Phase I study is complete and that Phase II — testing IGF-1 vs. a placebo — is still enrolling.  The Phase I results are now being tallied and prepared for publication, possibly as early as this fall.

      • Aeroberts59

        My Niece is still involved in Phase I and Phase II is going to start in Jan.

        • Islamali5

          How old is your niece ? My daughter will be two years old next October 2012. Did she take 20 weeks of IGF 1 ? Any imprpvements other than motor skills like cognition, responding to her name, speech and hands function? I really appreciate your kind reply

        • Islamali5

          Hello Any news?

        • Islamali5

          Hello Any news?

  • muna osman

    thanks so much …Nancy

  • Z_vendal

    Is it possible to get I-GF-1 anywhere for purchase, at times, certain medications/molecules may not be available for the masses or be FDA approved but can still be manufactured/purchased privately

    • Nancy Fliesler (editor)

      I checked with Dr. Khwaja, and he says that the form of IGF-1 that’s under study (mecasermin [rDNA]
      injection) is only available by prescription, and is
      currently only indicated for children with severe primary IGF1
      deficiency.

  • Andre

    When do we expect the phase 1 results? Thanks

    • Nancy Fliesler (editor)

      The Phase I study officially ended in October 2011, and data are being analyzed in November and December.  Dr. Khwaja and colleagues expect to submit their results to a journal early next year, so when they’re published depends on the journal – could take another 6 months to a year.

  • Naeesnyder

    Any recent word on Phase II of the study? Praying to get our Ellie in. 

    • Nancy Fliesler (editor)

      The team tells me they are doing a lottery of the families who previously expressed interest, and hope to let all families know in the next couple of weeks. Feel free to email rettresearch@childrens.harvard.edu for details.

      • Laura

        Hi Nancy, do you see tremendous improvement in your niece after phase 1? or just minor improvement? Is it possible for me to contact the guardience of your niece? I would love to understand a little bit more about the trial process and result. I have a three years old with Rett and we feel lost and helpless.

        • Nancy Fliesler (editor)

          Hi, Laura, did you mean to address your question to Rebelle59? I’m just the editor of this blog, but maybe if you contact the study at rettresearch@childrens.harvard.edu, they could update you on enrollment status and perhaps (if it’s not now closed) put you in direct touch with other families. Good luck! Nancy

  • Anonymous

    Can someone kindly confirm is phase 2 of this trial has officially started? Thanks

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