OK.
So as Kev blogged about this morning, they figured out how to cure (or as the paper put it "rescue"/reverse) Rett Syndrome in mouse models.
At least one specific mouse model.
This specific mouse model isn't particularly like humans with Rett, in that the investigators designed the mice to be able to produce healthy MECP2 protein and then shut it off--BUT--here's the extra special tricky part--they would be able to turn it back on at any time, using injections of an estrogen regulator (estrogen, girls, girls get Rett...and I swear no hormone is sacred in autism research).
HUMANS with Rett don't have that happy little out. They have what is called X inactivation, with one healthy copy and one not so healthy copy of the gene per cell, along with a bunch of other genes on their X chromosomes, and whichever one is on...is on. And that's life. This is also why VERY few boys with Rett live, mostly those with XXY karyotypes. But back to the study.
So they have these genetically engineered mice who have a Rett phenotype but the genotype is kind of a cheat. Then they first inject them with bigass doses of tamoxifen. Oops. Half the mice DIE. Shock to the system. You just cannot take a body, a brain, that worked one way for however long-in the case of the mice, around 4-6 weeks, life expectancy of 11 weeks, and then suddenly fill it with a protein that works TOTALLY DIFFERENTLY and expect it, like, not to cause massive problems.
Wait. Autistic people have been saying something awfully similar for years. I think those dead mice (9/17) just proved it, didn't they? Poor mice. I'd have kept an autistic or Rett mouse.
But back to the study. They tried again. This time they gradually increased the tamoxifen dose. Fewer fatalities, but some still died (and I do not have the number in front of me, no). The ones who were "rescued"-and yes, I find that word insulting-appeared normal, insofar as a Rett mouse can appear normal-no hindlimb clasping, movement was better, not as listless, less obesity-not a feature of human Rett syndrome. There was no mention of 'autistic behavior' or seizure activity, which are the symptoms that at least start out as most distressing to parents and people with the condition, respectively. For those who do not understand, it bothers little Hailey's mother that she doesn't look at her. It bothers little Hailey that she has seizures, which likely also distress her mommy but not as much as the whole acting autistic thing because of the 24/7 nature of being autistic. Of course people vary. Respiratory patterns in the mice also improved, as did their lifespan.
Now.
Repeat after me.
Mice.
Are.
Not.
Human.
It's all very well and good to find ways to decrease apraxia and the whole forgetting to breathe thing. Somehow I doubt that messing with estrogen is the way to do it, seeing as we aren't genetically engineered humans. No, this won't help your autistic kid be NT, especially if your autistic kid has no MECP2 abnormalities. Sorry, but it won't "rescue" your girl with Rett either.
The point of this study was to see if Rett was a condition with a point of no return, from which there is no restoring of functions like purposful movement. The answer is no. It didn't say HOW to restore such things in humans, merely that the brain cells ain't dead yet. They aren't even damaged, particularly, just prevented from doing their Thing.
This was not a cure of anything resembling an autism spectrum condition as found in nature.
This was in a setting in a lab, very controlled, and is light years away from human application.
Trying this on any kid at this stage in the game would be crazy. Yes, crazy.
Friday, February 09, 2007
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19 comments:
Thanks, Kassiane. I appreciate your writing this.
Sorry if this is a repeat comment, blogger seems to have lost my previous one.
"This was not a cure of anything resembling an autism spectrum condition as found in nature."
But a condition found in the imaginative speculations of someone....who needs to learn what autism really is.
"Now."
Okay...
"Repeat after me."
Yes...
"Mice."
Mice...
"Are."
... are ...
"Not."
... not ...
"Human."
... human ...
Now, I had no problem with repeating that, since I am one of those who knows that a mouse model of anything is of limited usefulness.
I wish all my supposed colleagues were as aware of this fact.
This is a very interesting story, actually: Kassiane blogs and shows how she has a better grasp on things than many scientists.
I'm not joking, either.
My daughter has autism and IS miserable!! She would probably love to contribute to a blog such as this, but she CAN'T. She has full-blown RETT SYNDROME. She cannot walk, talk, or feed herself. About half of the food that SOMEONE ELSE puts into her mouth falls right out the front. She is responsive and seems to know things, but cannot express what she does know so we can't evaluate the level of learning that she has. I'm sorry that some mice died. However, I am glad that they have proved that the neurons in her brain can function well when the right conditions are in place. And, no, I don't expect a miracle cure in the next week or even year or two. However, I'm glad that these researchers are trying to find some way to release these girls with this disorder from this prison, from this HELL! I don't feel at all deceived by this research and I don't feel that the researchers have tried to deceive anyone. I am a school teacher. I believe in diversity. When I see autistic children in my school, I celebrate. I love them, and I wish my daughter (whom I love very much also) could function as well as they can. I'm never certain when I go into her room in the morning if she will still be alive. Her brain may have forgotten to tell her to breathe in the night. It breaks my heart that she cannot tell us her fears or her wishes, and that she has to only watch as other children play with toys and hold books or dolls. Please don't be so quick to judge this particular situation for the rest of us....
Hi
There is another manuscript published on the topic, by other group
Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2
IS your daughter miserable, or are you miserable watching your daughter? There's a distinction.
The researchers didn't, I don't believe, intend to decieve anyone. I didn't say they did. The media, however, decieved a lot of people. I saw headlines saying "Autistic mice cured!" and all sorts of things like that implying that autism and Rett were things of the past.
Unless your daughter has a stop/ cassette genetically wired into her DNA (something no sane loving parent would do to their child, because...well...duh) this isn't a CURE. This is proof of something that is very important to your daughter though:
That there is hope after FULL REGRESSION IN RETT.
I'd say that matters more than full phenotypical reversal in mice, no? So what if they're like "normal" mice now, there is proof that the neurons in your beautiful little girl's head can DO STUFF. Stuff besides handwringing and seizing and forgetting to send all the digestive stuff the right way and ignoring her movement commands...they can learn to DO WHAT SHE WANTS THEM TO DO.
That's way cooler than undoing a genetic engineering job that you did in the first place.
Well, they have to start somewhere. I wouldn't expect they would carry out the same exact procedures on human patients. And, YES she is miserable and frustrated much of the time. My concerns are for her sake, not mine. I just got her to bed tonight, and she had quite a difficult time of relaxing and getting to sleep even though she could hardly hold her eyes open. And tomorrow morning, just like every other morning, when I go into her room to get her up I will hold my breath hoping she didn't stop breathing in the night! I do not know if you are a parent or not (I'm assuming no), but it's heartwrenching to watch the frustration and the tears she experiences each and every day of her little life, and there's nothing she can do about it. Again, I think the point of the study was not the "genetic engineering" job that they did and then undid. It's the fact that the neurons survived and "recovered" after quite some time, in some cases, of deficient amounts of a critical component.
rodsdoll,
I can relate to some of your struggles and worries as a parent of an autistic child who is also diagnosed with ADHD-impulsive, epilepsy, and possibly bi-polar.
The autism, ADHD, and possibly bi-polar isn't what frightens us. It is the seizures that Edith has been proned to have that do. Her autism and ADHD, bipolar aren't going to kill her. Her epilepsy very well could.
As you might know any generalized tonic-clonic seizure that lasts over 10 minutes in duration can cause brain damage if not death. Edith has had quite a few of these seizures lasting an hour or more before they are stopped. (and when I say quite a few, I mean more than I can count on one hand.)
I can relate to your anxiety each morning. What if Edith had a seizure during night that killed her? Currently she sleeps with us, but even that is no guarantee we would know.
I know the agnony of standing by her bed in the ER watching her seize continuously while nothing the medics are doing is causing it to stop. Eventually the panic feeling of "what if this is the end?" begins to grow. I eventually find myself repeating the same plea for her life to God over and over again irrationally, since He probably heard me the first time.
The last long seizure that Edith had was discovered by luck when my wife had gone up to our room for something and discovered Edith seizing.
Of course, Edith doesn't have Rett's so she obviously has fewer life threatening challenges to face. The only one I can think of is her tendancy to dash out in the street without looking for cars, (she's only 5, hopefully that will change).
The way we get by is in the belief that Edith is in God's hands and He obviously is doing a wonderful job taking care of her. Although, she has had a lot of seizures lasting well beyond 10 minutes, she doesn't appear to have suffered any brain damage from them. Little things about her might change, (i.e. used to like ketchup, now doesn't want it), but beyond that she has come out of each one pretty much unscathed.
I know it might sound tacky but hang in there. I know that it can be tough. I wish the very best for you and your little girl. There is no telling what the future holds for your daughter as she grows up. Some things might change.
I believe Kassiane is a good example of being able to lead a productive meaningful life with RETT's Syndrome.
Perhaps it will be the same for your daughter. I certainly hope so.
Hi Kasianne,
I think the problem is not with this study but with the media coverage. If people are so inclned they can find link to the complete text on Kev's Left Brain/Right Brain blog. It concludes that,
"The experiments do not suggest an immediate therapeutic approach to RTT, but they establish the principle of reversability in a mouse model and therefore raise the possibility that neurological defects seen in this and related human disorders are not irrevocable."
In a video press release Dr Bird said that,
"Tamoxifen only works in this context because the mice have been set up to respond to it by activating the MECP2 gene. But in order to get them to do that it was necessary to alter the struture of the gene in specific ways. It would have absolutely no effect in humans."
That will not deter the "cure autism at any cost" brigade. Dr Deth is already blithering on about methylation and anti-oxidative stress. For me the take home message from this research is that if and when they find a way of correcting the faulty expression of MECP2 in people with Retts it should alleviate symptoms that were previously thought to be permanent. If that helps Rodsdoll's daughter to enjoy an easier life it has to be a good thing.
Mkay, to make something perfectly clear, asking if I'm a parent is irrelevant and means "I have no actual logic to go on". It's also damned annoying. Have you ever awakened in the morning one day and had your hands behave like alien beings, only been unable to express such? No? Do you have life threatening seizures? No? Ok. Then my parental status is a nonissue because I have RETT status which trumps PARENT status as far as, like, experiencing Rett is concerned. This blog isn't about being a parent, it's about autistic spectrum rights.
If someone can tell me where I said improving health and praxis is a bad thing, please do. I never said that. I had to design my OWN OCCUPATIONAL THERAPY to do just that. I have to fight 5 doctors in the next 10 days to do just that, for myself.
Nor did I say the RESEARCHERS mislead anyone. I said *just*the*opposite* and that the media are misleading people. Literacy: it's a good thing!
I am pro progress. Pro health. I'm not big on curing things that don't kill people but do shape who they are. Praxis problems--and what people see as classic Rett is mainly the praxis problems, if you look at speech preserved variant you see people a lot like me--aren't who people are, they're a pain in the ass. Autism DOES shape who people are, just ask an autistic adult.
And frankly, I am against false hope. That one is the media's fault, and the fault of the quacks who deal more with classic autism than with Rett who are likely to leap on this since their ex golden boys got in trouble for their LAST messing with hormones treatment. I'm against messing with hormones that don't need it, in case that needed stating...
LITERACY - It is a great thing. Oh, and by the way. You never mentioned the media in any of your previous entries, so therefore it reads as if you said the research is misleading. Also, in your last entry paragraph 4 makes no sense at all. You might want to work on that literacy Thing...
Kassiane did reference what was posted in Kev's blog, which does link to the media coverage, as well as extensively discuss reactions of various other human beings in regard to the media's word choices.
After reading both, it appears she was operating on the assumption that everyone reading what she posted had also bothered to read what Kev posted.
In its own way, all research is misleading when irrational reactions on the part of humans occur. The article might be more accurately titled "Reversal of Neurological Defects in a Controlled Mouse Model of Rett Syndrome." This article may be misleading if the reader neglects to keep in mind that all the mice tested were created specifically for the project with a convenient trigger-- the Lox-Stop cassette.
At this point in time, humans are not lab grown with such conveniently controllable genomes. For anyone to attempt to stretch this research to being anywhere near applicable to humans yet is ludicrous, even bordering on cruel seeing as it preys on the hopes and fears of anxious parents such as Rodsdoll, whom may or may not have time to research all the referenced material for themselves.
More research needs to be done, specifically on mice with less specially engineered MeCP2 mutations. All I am seeing proven from this article is they created a convenient on-off switch with a good chance of the "off"... well, offing the mouse.
Rodsdoll: "Also, in your last entry paragraph 4 makes no sense at all. You might want to work on that literacy Thing..."
Okay. Let's see. I'm dyslexic, so if I can make sense of her paragraph 4, anyone should be able to.
"I am pro progress."
Kassianne likes to see progress.
"Pro health."
She likes people to be healthy.
"I'm not big on curing things that don't kill people but do shape who they are."
She doesn't go for the idea that one should get rid of aspects of personality/etc that define (or lead to a definition of) who someone is at a fundamental level.
"Praxis problems--and what people see as classic Rett is mainly the praxis problems, if you look at speech preserved variant you see people a lot like me--aren't who people are, they're a pain in the ass."
Well, here we have a sentence with a sub-clause. She says: "Praxis problems aren't who people are, they're a pain in the ass."
And she's right. Praxis problems can always be a liability (I'm also dyspraxic... it means I don't get to do a lot of things... I can't operate a lathe, despite having been taught from being 13 years old how to do it... my dexterity isn't there for it; and I can't play a blistering guitar solo as I might want to do; and there's things like paradiddles I have problems with when I'm drumming). And my handwriting is bloody attrocious. Yes, I'll say that praxic problems are somewhat of a pain in the arse.
In the sub-clause, Kassianne says: "... and what people see as classic Rett is mainly the praxis problems, if you look at speech preserved variant you see people a lot like me ..."
The most prominent observable issue, says Kassianne, in Rett's syndrome (as defined in the criteria) is the problems that surround voluntary movement. And Kassiane says that, if you look at Rett girls/women who still speak, you see people who resemble her.
"Autism DOES shape who people are, just ask an autistic adult."
Kassiane says that autism (being a developmental issue) is crucially interlinked with who one is. I agree with that. As a psychologist and as an autistic person.
What was wrong with that paragraph?! I understood it well enough (I'm sure that Kassiane will correct me if I'm wrong!)...
Rodsdoll, "You might want to work on that literacy Thing..."
Especially since one doesn't use a capital letter to begin a noun used in mid-sentence unless the noun is a proper noun.
I also teach English. My students, who are Finnish, wouldn't do that (and neither would their dyslexic teacher!).
I agree with David.
Kassiane's position is quite clear for anyone who wants to understand it.
Mike: "Kassiane's position is quite clear for anyone who wants to understand it."
Thank you, Mike.
That was my point exactly. Can you tell that we spectrumites tend to be wilfully misunderstood a lot?!
I certainly agree about the media coverage. I read about the study in three or four different places and the headlines were 'sensationalized' relative to the content of the articles.
shawn,
The headlines usually are.
Wow all Autism blogger here....a good place...
Hi Kassiane,
Just wanted to say hi and to tell you that I am your blog new reader...
Health Watch Center.
Self Hlep Zone
but wouldn't testing on mice lead to testing on rats then pigs then monkeys and finally humans
the nature of the scientific method is start at something that has a simple genome ( a house fly) and then move up in complexity( rat, pig monkey, an so on) as the understanding of the problem gets better and the methods for testing ge the model gets closer and closer to humans
but then i suppose its a bit above the mead to understand the nature of scientific research
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