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01/11/2019

Thoughts on the C-word

By Rachael Stevenson, Co-Founder, Executive Director, Reverse Rett

During #Rett Syndrome #Awareness month, some awareness has been drawn to the word cure; what it means for people with Rett Syndrome, whether it is right to use it, or indeed, right to be trying to find one at all.

According to Lexico, powered by the Oxford English Dictionary, the definition of the word is as follows:

Cure (noun)

  1. A substance or treatment that cures a disease or condition

2. Restoration to health 

3. A solution to a problem 

The origin of the word comes from Middle English and Old French, curer, both from Latin, curare, ‘to take care of.’ The meaning of the noun comes from ‘care, concern and responsibility’ in part, spiritual care.

Of course modern day definitions have evolved, just like everything else. 

At Reverse Rett, we often highlight the difference between treatments and cures in terms of the research we fund.

When we say treatments– we mean drugs or therapies aimed at relieving people of one or more troublesome symptoms.

When we say cure-we mean drugs or therapies aimed at resolving the underlying cause of the condition, and we hope, resolving as many symptoms as possible at the root.

But is it right to look at Rett Syndrome as a problem at all?

In many disability groups, conditions such as autism and deafness, there are activists who seek to have their condition recognised, not as an illness or disability but as a different experience or way of life.

In Rett Syndrome, many children and adults are so severely impacted by the condition that their ability to share their views on this is severely hampered.

Many young people and adults with Rett are unable to walk independently, speak or use their hands. Some are able to use eye gaze technology and other methods to communicate. Very few have the ability or opportunity to communicate more complex thoughts, feelings or expectations.

For many families, this is not the crux of the problem. We love our children unequivocally and unconditionally. We value them, just as they are and the unique gifts they bring to each of our families, forever changed by having them in our lives.

Sadly Rett Syndrome isn’t just about impairment or disability alone.

People with Rett are also affected by seizures, by breathing and cardiac irregularities, problems with their bones and joints, difficulty eating, swallowing and digesting food, chest infections, regulating bodily functions, such as temperature, sleep patterns and more; their erratic autonomic and emotional states bringing about severe agitation and anxiety affecting them throughout their days and further exacerbating physical symptoms.

Children and adults with Rett Syndrome of any age are at increased risk of sudden death as well as death from secondary complications of the condition (1).

Fundamentally for so many of us who love someone with Rett, curing the disease isn’t about changing the person at all; but about increasing their chances of staying healthy, well and alive.

So if it isn’t about disability and instead about wellness or health, where does swallowing fall? What about the ability to eat orally, full stop? What about walking?

For example, we know that standing is closely linked to health in Rett Syndrome; in terms of prevention of scoliosis, improved digestion and constipation and bone strength. The current Rett Disorders Alliance Health Checklist (p.23) recommendation for those unable to stand independently is that they should use a standing frame for a minimum of two hours a day.

Can we hope for this to be improved by a cure? Is this changing a person? Who they are? By wanting them to be able to stand and walk?

When we first started Reverse Rett in 2010, the word cure was never really mentioned. We had only just witnessed the successful reversal mouse experiments (2). There was not yet any potential tangible way to replicate research progress in humans (3). Gene therapy was not the buzzword it is today, with treatments for various genetic diseases popping up in the news on a regular basis.

A series of successful experiments (4) and gathering research momentum (5) changed the outlook. Language started to shift, if only so that organisations such as RSRT, Reverse Rett and others could differentiate between their varying focuses on different research projects.

A 2013 survey by the U.K. Rett Disorders Alliance identified over 50 symptoms of Rett Syndrome, varying from person to person. Different families considered different symptoms to be more problematic than others. No doubt, so do the patients and their views may not be aligned with their parents.

If you are the parent of someone with Rett Syndrome, I ask you to consider this. If you were to wake up tomorrow and found yourself unable to walk, see or speak, would you accept it was not a problem so long as your family still loved you? How would your life change? Would you think it was ok to hope that one day things might be different?

There are so many symptoms of Rett which we don’t yet fully understand. The condition is complex; symptoms are intertwined. What is more simple is the genetic cause, a single gene mutation which, when corrected, leads to a recovery of function, health and a normal life span in mice.

As research organisations with finite resources, we must ask ourselves; do we invest largely in experimental medicine aimed at alleviating symptoms one or two at a time or do we boldly aim to correct the underlying problem, the lack of a vital protein caused by this genetic mutation and knock out as many of the symptoms as we can in one fell swoop?

Of course those of us living with Rett Syndrome today are necessarily focused on here and now. Many of us want something/anything that can help our child today. We want something/anything that will keep them well. Something/anything that will keep them alive.

At Reverse Rett, we are supporting the development of emerging treatments aimed at alleviating symptoms. We are recruiting patients for clinical trials and support participating families with the logistics of study visits. We are working hard to improve UK clinical provision so that complex patients with Rett have access to holistic specialist care. And yes, we wholeheartedly support RSRT projects at the University of Edinburgh and beyond who are unapologetically going for the cure.

Will this happen in time for our children living with Rett Syndrome today? We don’t know. Nobody knows for sure that it won’t, either.

Science is as open to serendipity as any other discipline. We can’t know how the AveXis Gene Therapy trials will go until they happen. Technology evolves faster than any of us can even read about it; things that humans have never conceived of, are happening every day.

Is it right to hope that one day things can be different for our children? That their lives could be less difficult? That they could have more choices and more opportunities in living it?

The answer to this is even more ambiguous. Hope is a feeling, an expectation, an intervention even. No one owns it. Whilst the science behind Rett gives validity to our hope, it is not required.

Hope is free. Anyone can have it, any day, whenever they like. For many of us, it comes and goes. Whether we can sit with it in relation to the individual we love, is deeply personal.

My own daughter, Amber, who has Rett Syndrome, is 24 now. I started this work because I wanted treatments and yes, a cure for her. Or at least, a better chance. A better choice.

I wanted and still want her to be well and alive. Her disability is immaterial to me.

Would she want to walk again if such things were possible? Would she want to speak?

To get off these many medications and away from her daily struggles with breathing, anxiety and stomach problems?

That we have even reached a place in time where this dialogue is open is surreal.

I hope that I can sit with it a little longer. And that someday, these choices will be hers to make.

End Notes

1. Tarquinio D. C., Hou W., Neul J. L., Kaufmann W. E., Glaze D. G., Motil K. J., et al. . (2015). The changing face of survival in rett syndrome and MECP2-related disorders. Pediatr. Neurol. 53, 402–411. 10.1016/j.pediatrneurol.2015.06.003

2. Guy J, Gan J, Selfridge J, Cobb S, Bird A. Reversal of neurological defects in a mouse model of Rett syndrome. Science. 2007;315:1143–7.

3. Garg S.K., Lioy D.T., Cheval H., McGann J.C., Bissonnette J.M., Murtha M.J., Foust K.D., Kaspar B.K., Bird A., Mandel G. Systemic Delivery of MeCP2 Rescues Behavioral and Cellular Deficits in Female Mouse Models of Rett Syndrome. J. Neurosci. 2013;33:13612–13620. doi: 10.1523/JNEUROSCI.1854-13.2013

4. Lieselot L. G. Carrette, Chen-Yu Wang, Chunyao Wei, William Press, Weiyuan Ma, Raymond J. Kelleher, Jeannie T. Lee. A mixed modality approach towards Xi reactivation for Rett syndrome and other X-linked disorders. Proceedings of the National Academy of Sciences, 2017; 201715124

5. Sinnamon JR, Kim SY, Corson GM, Song Z, Nakai H, Adelman JP, et al. Site-directed RNA repair of endogenous Mecp2 RNA in neurons. Proceedings of the National Academy of Sciences of the United States of America. 2017;114(44):E9395-E402. doi: 10.1073/pnas.1715320114. PubMed PMID: 29078406.