Up the Garden Path? A short conversation about Rett: research, treatment and the validity of hope

The following extracts are from a Facebook conversation between Nicky Perriman, mum to Robyn and Rachael Bloom, Executive Director of Rett Syndrome Research Trust UK and mum to Amber in response to the following Facebook post:
Rachael Bloom2012 may see the efforts of the scientists and the donors who support them begin to bear fruit – a year that could prove to be paradigm-shifting in how we think about fighting Rett Syndrome. A year where we may begin to test, via clinical trials, whether what works in the animal models will actually work in children.’
Please read the following message from Monica Coenraads-bottom line-the time for action is NOW!http://www.rsrt.org/rttwatch/2012/Executive-Director-Letter.html

Nicky Perriman I wait in hope as does every other Rett Syndrome mother/father…. But I feel we are being led up the garden path. I have recently looked into Rett research for the first time in my life since my child’s diagnosis…. Several times I have come across how this has been reversed in mouse models, each stating that you are still unsure that you can reverse it in humans… I remember going to the Rett Syndrome Association Family Weekend when Robyn was first diagnosed and being told about reversals in mouse models (or it was close) I remember being young and naive, and very new to Rett and looking at these mice and being sucked in that a difference could be made. Years later our cure is still no closer-the research doesn’t seem to have come much further. Now this is either my failure to read properly or my hopes are too high.

Rachael Bloom@Nicky Perriman, I am really glad you have asked these questions because this is certainly something that a lot of people are talking about and questioning and it’s important that we get it out in the open and discuss.

The publication that demonstrated that Rett Syndrome could be reversed in the mouse model came out in February 2007:   http://www.sciencemag.org/content/315/5815/1143.abstract?ijkey=wallzb5aq40%2Fk&keytype=ref&siteid=sci

As you know, Rett Syndrome is most commonly caused by a gene called MECP2 which makes a protein, also called Mecp2, which is necessary for normal brain function. When the reversal was done in the mice, the researchers did it by genetically engineering the mice so that they had a ‘switch’ whereby, they could let the mice develop without the protein (they developed Rett symptoms) and then switch the protein back on at will (the symptoms went away). Our children don’t have a switch, so it was not possible, after the reversal experiments, to just translate what happened in the mice, into humans. Researchers have to find other ways to restore the protein at the right levels.

So in collaboration with US based RSRT; Rett Syndrome Research Trust UK has funded 12 treatment-focused projects in the last 18 months. Some of these are looking at how to replace the protein at the right levels; some are looking at addressing the underlying problems with the gene. Some are looking at bypassing the faulty gene, or finding ways to use other genes to help counteract the problems with MECP2. Others are looking at improving specific symptoms, or even just improving the symptoms at large without having to address the underlying genetic causes.

Nicky Perriman Well that sounds pretty good… A month ago that woulda gone right over my head lol. Would you think I’m correct in thinking that, this cure, protein replacement etc. would benefit younger girls i.e. recently diagnosed. Not that I’m being pessimistic but I just think if Robyn received a cure/reversal of any kind she would still be behind X amount of years. She would have to start learning from being a newborn baby. Sorry to pose these questions x

Rachael Bloom They are good questions. The data from the reversal experiments shows that the reversal was effective in models of late stage disease. The quote from the abstract from the paper cited above says: Using a mouse model, we demonstrate robust phenotypic reversal, as activation of MeCP2 expression leads to striking loss of advanced neurological symptoms in both immature and mature adult animals.

Nicky Perriman I also want to know if they know what will the reversal mean to us? i.e. if they do find a way to put the protein back?  Is it expected to cure the epilepsy etc.? x

Rachael Bloom Let’s start by clearing up the difference between treatments for Rett and a cure for Rett. An effective treatment should really help or even take away a particular symptom or set of symptoms. As you know firsthand, there are so many severe symptoms that make up ‘Rett Syndrome’ that even controlling one or two could dramatically improve a person’s quality of life. A cure on the other hand, should completely restore someone to health. Until whatever treatments and cures become available for and are tested through human trials, no one can say exactly what is going to happen. Certainly, the videos of reversal in the mouse model show a dramatic regain in function. See here for before:

and here for after:
the mice do go on to live normal lifespans, where, without reversal, they died within days.

You can read an article about understanding the reversal in more detail here: http://www.rsrt.org/research/understanding-the-2007-reversal/

Nicky Perriman Yes I saw that. It’s very exciting stuff, I just wonder how it’s all going to work x

Rachael Bloom  I think we all do. And the answer is that we just don’t know. My daughter is sixteen now. I can’t predict how she will respond to treatments and cures when they come. What I hope, is that, after a lifetime of disabilities and medical complexities, they give her a chance to live more freely and maybe even the chance to improve on some things, to be able to benefit from therapies, to make actual progress, instead of working so hard all the time just to bat a barrage of difficult symptoms off. I want to make one thing clear though; there are some people who get involved with causes and charities because they are nice people who care about the whole world. That isn’t me. I can hear my daughter struggling to breathe every night when I go to bed. The fact that the scientific evidence is there to support the fact that reversal is hypothetically possible for models of late stage disease is what gets me out of bed in the morning.

Nicky Perriman I feel so sorry for the mice, and I hate mice. But I know it’s essential for our girls to have treatment.

Rachael Bloom 🙂 re mice. I’m a vegetarian-never eaten a mouse in my life but I feel more sorry for our girls.

Nicky Perriman Oh yes indeed. I’m petrified of mice lol. On a positive note I actually see Robyn purposely dancing just her head, but it was to the beat. It was amazing. Her dystonia is so bad and 3 of us notice these tiny head movements. It’s lovely when you see a simple thing like that they we take for granted. All I want is for her Dystonia to be controlled, that’s all I ask loll x

Rachael Bloom I would take breathing x

Rachael Bloom Just going back to Monica’s letter though…despite the fact that we have now had almost five years of knowing about reversal and rumblings of treatments and cures where there were none before, the thing that was different about Monica’s letter, was that this is the first time RSRT (US) has publically stated that we are moving into a time where research coming out of the lab may have real clinical implications: ‘2012 may see the efforts of the scientists and the donors who support them begin to bear fruit – a year that could prove to be paradigm-shifting in how we think about fighting Rett Syndrome. A year where we may begin to test, via clinical trials, whether what works in the animal models will actually work in children.’

There’s a reason that this needs to be said, and it isn’t about raising hopes -it’s because it will cost a lot of money to take this work to the next stage and we need help. These are good problems to have though-hope/yes/no-bad or good? (Great to have a choice, there wasn’t one when Amber was diagnosed) Need more money to ensure promising research developments can be carried through to the next level?? Scary…and a lot of work…but better than more years of no next level to move to… Will we get an all-out cure (get up and walk Lazarus!) or just significant improvements??….either of these and anything in between are surely better options than what is currently available, I think. I hope. Yes, I do. I do hope! Every day. I think it’s allowed. And I am waaayyy way down that garden path. And funnily enough, there are a lot of scientists here too:)

Nicky Perriman Lol…. Well we need to raise some cash then.

Yes, we do. Huge thanks to Nicky for her kind permission to share this conversation and great appreciation to Elijah Halford for the splendid picture below demonstrating why he and brother Jack did this fundraising in hope for a better future for their sister, Grace, just a few weeks ago


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About Rett Syndrome Research Trust UK

Rett Syndrome Research Trust UK is the only UK charity exclusively focused on the development of treatments and cures for Rett Syndrome and related MECP2 disorders. Registered charity number: 1136809
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One Response to Up the Garden Path? A short conversation about Rett: research, treatment and the validity of hope

  1. Thank you for publishing this article.Nicky you asked some key questions that many of us parents have wondered & talked about amongst ourselves especially those of us with older girls.Rachel you had the right answers & an excellent hopeful perspective that I also know all of us parents share.I am hopeful in the scientific discoveries made thus far and in the knowledge that so many various labs worldwide are undertaking a mass effort to cure &/or treat rett syndrome.It is my fervent hope that our girls & future girls/boys will be spared from this devestating nuerological disorder!GODSPEED!

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