Friends

Amy came home from school the other day with a hand-made bracelet and a note from her teacher: "The bracelet was given to Amy by T. She was thrilled." It consisted of several tubes of coloured card threaded onto a piece of wool - just the right size for her narrow little wrist. She was still thrilled when she got home.

T is Amy's special friend and admirer. He's in an older class at her school, and ever since she started there, he's had a 'thing' for her. He comes to visit her every day, and she loves the attention. We just have to mention T's name and she beams. One day when I was on my way to class to pick her up, he waylaid me: "Amy. Amy's mum. Red class. I love her." "That's so lovely, T, " I said. "Why do you love her?" "I love her hands. I love her glasses. I love her face."

He's more verbal than many of the kids at the school, but even with limited words he expresses himself more perfectly than most people. There was a day when I was with the two of them, and he was chatting and Amy was smiling. Then suddenly Amy's face changed and she began to cry. (A very typical scenario.) "Oh. Oh no. Oh Amy. Amy, sad face."

From my point of view, T is more important than I'm sure anyone realises. He makes Amy happy. He is someone she has an independent relationship with, unorchestrated by me. The fact she has a friend that I haven't arranged for her - and not someone she just sits beside, but who she interacts with - makes me yearn for her to have more. And it makes me realise how hard it is to populate Amy's life with the proper sort of friends that little girls her age usually have.

She knows a lot of people, and a lot of people know her, but honestly? She hardly has any real friends of her own age. Outside school, she spends a lot of time with adults. (And with her big sister of course - thank goodness for her.) Other children her age don't pay a whole lot of attention to her - I guess because she's slow to respond to things, and because she's so inexplicable: happy and engaged one minute, and miserable and withdrawn the next. Understanding that is a challenge for anyone, let alone the average five-year-old. But still, it's hard when friends who have children the same age don't include Amy in invitations to do the things their children are doing: I can't pretend it would always be easy, but sometimes she and I both need to be reminded of the things that five-year-old girls do.

The other thing that makes her smile

It turns out that the other thing that makes Amy smile as much as playing the piano and going swimming is riding on a merry-go-round. She went to the fun fair today with her sister and cousin and had a lovely time.

In the past, she has slightly 'tuned out' this kind of experience - screwing up her eyes or acting jumpy and uncomfortable when we move her or try to put her on things. There have also been times when she's seemed to enjoy it afterwards - not smiling much at the time, but responding happily when we talk to her about it later. But today she loved every moment. The more she went, the more she smiled.

Reminds me that I really need to find somewhere that offers horse-riding for children like Amy. It's all part of the endless quest towards upright-ness. And more pertinently, I think she'd love it.

Ah, that smile...

'Brave poor things'

Sometimes I find myself wondering (in idle moments, when my brain is having a break from wondering about all the other stuff that bothers it) what living with Rett syndrome was like through history. I don't know how long the human MECP2 gene might have been mutating to cause the symptoms that we now know as Rett syndrome, but I assume it must have been going on for a long time - centuries - before anyone even began to understand it.

For all the challenges that severe disability presents for children like Amy and families like ours - and for all the way there is still to go before society in general understands and accepts and includes - at least it's accepted that our children will be with us, and that they have potential that deserves to be fulfilled. (Well, mostly it's accepted.) And we have the freedom to express the full range of thoughts and emotions that go with our experience, beyond being models of brave acceptance. (Again, mostly.)

Yesterday I listened to a heartbreaking piece of radio on the lives of disabled children in England in the nineteenth century. (It's part of Peter White's excellent Radio 4 series, 'Disability: A new history' - do psyche yourself up emotionally and have a listen.)

Those Victorians, with their combination of relentless sentimentality and religious fervour, have a lot to answer for. What they did was use the disabled child as a propaganda symbol and a moral message: if this child can put up with their lot in life, then so should everyone. Their aim was to impose contentment, and the voices of children themselves were non-existent.

Of course a child like Amy herself probably wouldn't have been around long, back then. Looking 'normal', she'd have been spared the fate of newborns with obvious congenital defects, of being "put in a basin and left under the bed", according to the programme. But her heart condition was untreatable, so she wouldn't have lived to become the object of charitable pity, like so many children who were deaf or blind, or left disabled through accidents or diseases such as scarlet fever.

Pity expressed itself through the explosion of charities to 'save' disabled children. To save their souls, that is, not save them from society's ignorance or prejudice. They were seen by these charities as poor, pitiful objects - an organisation actually existed that was called 'the Guild for Brave Poor Things'. Their motto - I'm sorry -  was 'happy with my lot'. And - I'm even more sorry - this charity hung around until the 1980s. (Although known in latter years as 'the Guild of the Handicapped'.)

It seems horrifying now. Outlandish, outdated, toxic in the way it presented people with disabilities as non-negotiably 'other'. But this perspective has had a lasting influence on perceptions of people with disabilities in this country: not only are they are often seen as needy and pathetic, they (or their carers) have to act in a certain way to get the support that enables them to function as autonomous individuals and not be 'needy' any more.

It would be comforting to think the 'brave poor things' perception was all in the past. But I fear it isn't. It's just more subtle now. And that makes it harder to get rid of.

On not avoiding

There's only so long your teeth can stay gritted. For a long time I thought you either had to stop looking at other people's children entirely (not really practical) or look in a detached, disinterested way. (Oh yes, a child standing up/playing with toys/saying words.) But recently I find I can look and be a teeny bit pleased when I see a friend's baby doing what babies should - gaining uprightness, playing with their reflection in the mirror, growing up. I still feel sad and mad, but manageably so. It's not my friends' fault, after all. This is their child, behaving like most children do - and this is my child, who I love and am no less proud of, but who is different and always will be.

I hate the condition that limits Amy and makes her so uncomfortable. And there are days when I hate the world for seemingly making everything harder. But it would be a shame not to enjoy all the fab and funny things that typical small children do. So now I let myself look and smile, and while 'what if...' and 'if only...' are still there, they take a bit more of a back seat these days. That's okay, isn't it?

A failure of narrative

Today I thought I'd do a nice uplifting little post about Amy's progress with the MOVE programme. She's sitting better, with less support, and her school planned to celebrate all the MOVE children with a special assembly this afternoon. Parents were invited along. I was looking forward to posting a picture of Amy in her new school chair that looks almost like a regular chair, and saying something sweet and optimistic about her.

Didn't quite work out like that. Because Amy hated it, as she hates most assembly-type situations - a crowd of people in an enclosed, noisy space is not her thing one bit. It began well enough, with a video of Amy and one of her class-mates sitting really well, in a variety of situations. But then when they began what they'd prepared, Amy started to cry. And cried through the entire thing.

I wished I hadn't gone. I was happy to see the video, but seeing Amy's real-time misery alongside all the other children who were happy and enthusiastic was hard. I know that she mostly likes school, and she does a lot of crying at home too, but sometimes the bigger picture is impossible to keep hold of. All I could see was my miserable, uncomfortable child crying, pulling her hair and rubbing her face, and the fact that she can now hold herself a bit more upright for a bit longer wasn't quite enough to keep me going. It was all I could do not to run out of the room there and then.

Something funny to end on though: Amy has learned that babies grow in mummies' tummies. (One of her lovely school support-workers is pregnant.) And she thinks this is the most amusing idea ever.

In search of a cure - this is how

As someone who is naturally wary of anything that sounds too good to be true, I was a bit resistant after Amy's diagnosis to cure-talk. I liked the idea, but felt the need to put some distance between it and myself. Because it was somehow too much to cope with, on top of everything else - hope being a harder thing to manage, sometimes, than despair.

It's different now. Now, I understand that a cure for Rett syndrome is not just a slogan, but the explicit aim of teams of dedicated scientists who have made unlocking girls with Rett syndrome their life's work.

So nowadays I raise funds for Reverse Rett. I talk and write about the search for effective treatments and, yes, a cure, and encourage others to believe it's possible. But I don't want people to support this compelling cause just because they feel sorry for us, or they think our girls are cute, or because we have a persuasive way with words. I want everyone to know that we haven't lost our marbles, or allowed grief and exhaustion to soften our brains.

Last month Rett Syndrome Research Trust hosted an event in New York City entitled 'Curing Rett Syndrome - how do we get there?' that explained ongoing research projects and the range of approaches to finding that cure. What follows was published today on the Reverse Rett blog: the science is complicated, but this is an attempt to explain it concisely and simply. Defeating Rett by outsmarting it: this is the aim.

CURING RETT SYNDROME: THE ONLY WAY TO DEFEAT IT IS TO OUTSMART IT

As a charity that is focused solely on raising funds to support research into treatment for Rett Syndrome and related MECP2 disorders, we talk a lot about finding a cure. But how will this happen? What do we mean by a ‘cure’? Why do we think there are such strong grounds for hope that an effective treatment is within sight?

To understand this, it’s important to understand what causes the condition. Rett Syndrome is caused by a single gene called MECP2 that mutates – changes permanently – at the point a child is conceived. It is this mutation that means the child will go on to have Rett Syndrome.

The MECP2 gene can mutate in a variety of different ways. Genetic testing – which is often used to confirm a Rett diagnosis – can pinpoint the exact type of mutation a child has. And parents often ask at this point what the prognosis is. As parents, we’ve all asked it: “What does this particular mutation mean for my daughter? How severely affected is she? What will she be able to do?”

But it isn’t quite that straightforward. There is no simple correlation between mutation-type and severity of Rett-symptoms.

Instead, there are two main explanations for differences in severity between different individuals – and understanding these will help us move towards effective treatments.

The first explanation is different patterns of X chromosome inactivation.

This refers to the number of cells in a girl’s body in which the mutated gene is active. The mutated MECP2 gene is on the X chromosome. Females have two X chromosomes – and in every cell of their body, one X chromosome is ‘active’, and the other is ‘silent’.

This active/silent pattern is usually random, which means that around 50 per cent of cells have one active X chromosome and 50 per cent have the other. But sometimes this pattern is not random, but appears skewed – where one chromosome is ‘favoured’ over the other.

If a girl with Rett Syndrome has a skewed pattern where the X chromosome with the mutated MECP2 gene is active in more cells than not, her symptoms will be more severe. (And vice versa – if the X chromosome with the healthy MECP2 gene is more active, she will be less severely affected.) We know from looking at identical twins with Rett Syndrome, who have the exact same mutation but different symptoms, that different patterns of X chromosome inactivation can make a significant difference.

If researchers could find a way of switching on the X chromosome with the healthy MECP2 gene – in every cell of the body – Rett Syndrome could potentially be cured.

The second explanation for differences in severity is the existence of modifier genes.

Looking at all kinds of diseases, we can see that the same disease affects different individuals in different ways. One reason for this is ‘modifier genes’ – something in a person’s unique genetic makeup that protects them against some aspects of the disease. Evidence suggests that some girls with Rett Syndrome have other genes that counteract the effects of MECP2 mutation.

If researchers could identify which genes protect against Rett Syndrome, treatment could be developed based on introducing these modifier genes.

The funds Reverse Rett raises in the UK are allocated to a range of research projects that aim to find treatment based on what we know about what causes Rett Syndrome and what affects the severity of the condition for individual girls.

There are three main approaches.

1. MECP2 as the target

We are particularly keen on this approach, because it attacks Rett Syndrome at its very root by seeking to switch off the mutated gene and switch on the healthy one. Research taking place at the University of North Carolina at Chapel Hill by Dr Ben Philpot and colleagues aims to activate the silent X chromosome that contains the healthy MECP2 gene. A big advantage of this approach is that there would be no need to deliver the healthy gene through gene therapy – because every girl with Rett Syndrome already has a healthy copy of the MECP2 gene.

2. Suppressor (modifier) genes

This is an example of the type of high-impact, high-risk project that we are keen to fund – because the potential rewards are so great. The aim is to identify which genes have the effect of suppressing, or modifying, the effects of the mutated MECP2 gene, as described above. It’s a bit like searching for the proverbial needle in a haystack. But Dr Monica Justice and colleagues at Baylor College of Medicine are beginning to see results. They are 15 per cent of the way through a project to ‘screen’ genes, and have so far found five potential ‘modifier’ genes.

One of the benefits of this approach is that it is helping researchers gain a better understanding of MeCP2, the protein produced by a normal, unmutated MECP2 gene. The exact function of this protein isn’t yet well understood, but one of the things it does is regulate other genes involved in brain function. It helps nerve cells (neurons) to function and to connect with each other. Girls with Rett Syndrome lack this protein, and as a result the neurons in their brain don’t connect as they should. (They don’t have brain damage: it’s the synapses – the points of communication between brain cells – that aren’t working normally.)

3. Downstream targets

We don’t always need to start from scratch with every treatment. There are drugs and treatments that are currently used to treat other conditions, but that may also have the potential to improve some of the most challenging symptoms of Rett Syndrome, such as breathing problems, seizures and disordered movements. Trials are already taking place in a number of locations, and we await the results.

Rett Syndrome Research Trust hosted an event in New York City in April 2013 entitled ‘Curing Rett Syndrome – how do we get there?’ Click here to watch a detailed presentation by Monica Coenraads explaining more about the current research projects we fund. You can also hear Ben Philpot discussing his work to find a way of reactivating the silenced healthy MECP2 gene as a treatment for Rett Syndrome.

A silent mystery

Amy came off the school bus at the end of the day on Friday with a 'special award' sticker - and no note in her book to say what she did to get it. I asked her if she got her special sticker in whole-school assembly, and she smiled - but I got no further. I so wish she could talk.

That's all.