Dr. Ricardo Dolmetsch on Autism Spectrum Disorder Research and Stem Cell Possibilities

25 Apr

Dr. Ricardo Dolmetsch is a professor at Stanford University. He is one of the keynote speakers for the IMFAR conference. Recently, Tom Insel, director of the National Institute of Mental Health interviewed Prof. Dolmetsch on his work. The video is up on the NIMH website, and I embeded it here.

I’m sure when many people read “stem cell possibilities” they are going to wonder if this is about stem cell therapy. No, there is no stem cell therapy for autism at present. What Prof. Dolmetsch is doing is taking skin cells and converting them into brain cells. He can then compare brain cells from autistic and non-autistic individuals and look for differences.

The idea is very interesting. If this method really does represent the brain cells in the individual, it would give some indication of the operation of those cells. What it probably won’t do, I suspect, is give an indication of long range connectivity or size of individual structures (e.g. corpus callosum, amygdala, etc.).

As you will hear (or read), Prof. Dolmetsch started working on autism after one of his children was diagnosed.

Here is the transcript:

Transcript

Announcer: NIH Radio… from Bethesda.

Announcer: Recently, Dr. Ricardo Dolmetsch, an associate professor of neurobiology at Stanford, spoke with National Institute of Mental Health Director Dr. Thomas Insel. Devoted to Autism Spectrum Disorder research, Dr. Dolmetsch and his colleagues have generated stem cells from children with autism allowing them to study how the brain develops in children with ASD.

Dr. Thomas Insel: I thought a good place to begin the conversation was to ask you about your interest in autism and how that happened. You’re someone who trained in calcium channels… worked on very basic problems in molecular biology and now you’re interested in autism…

Dr. Ricardo Dolmetsch: Right, when I first got to Stanford I was interested in a very basic question.. and um.. you know for a few years we worked on that and that was really exciting but it was very arcane. And then about I guess four and a half years ago, our son was diagnosed with autism. And so this really changed my…the direction of my lab. Actually, what really happened was that my wife and I got together and we thought a little bit about what we could do and we came up with a bunch of projects and one of the ideas was that we were going to just change all of our efforts and that’s how we started working on autism.

Dr. Thomas Insel: I know what you’re working on now has to do with induced pluripotent stem cells. And that’s a bit magical for many people… the idea that you can create a stem cell from skin or from some other differentiated cell. Can you explain what that is and how you think that will be helpful for studying autism?

Dr. Ricardo Dolmetsch: Our whole idea of development is that development is sort of a directional arrow. It’s kind of like spilling water. You can spill water but you can’t unspill water. And we sort of thought development went to the same way. You start out with an egg and you end up with a human- you don’t go backwards. But it turns out that that’s not quite true. So, this pioneering Japanese group led by Dr. Yamanaka developed this system that allows you to take for example skin cell or blood cell and convert it into a stem cell. And the way you do this is you introduce these four proteins that do something mysterious that nobody completely understands and it changes the cell and makes it into a stem cell. And that stem cell has the capacity to make every cell in your body including brain cells.

Dr. Thomas Insel: So you can make brain cells from the skin or blood cells of a child with autism.

Dr. Ricardo Dolmetsch: Exactly, so what this allows you to do then is you can then take.. for the very first time… you can make these tissues that you wouldn’t be able to access normally. So, so you can take the skin cells of a child with autism and you can make stem cells from those skin cells and then you can take those stem cells and you can differenciate them to generate basically little pieces of brain. And then you can analyze the development of those cells as well as their function once they’re mature and so this gives you insights that you wouldn’t have any other way.

Dr. Thomas Insel: So, when you do this in autism how do those brain cells that you derieve from skin differ in children with autism versus kids who don’t have autism.

Dr. Ricardo Dolmetsch: Well, this is something we’re still working on, right and I think we’re still at the very beginning. I think that the short answer is that we have so far only looked at a couple classes of autism and in those classes of autism we have learned something about how development is changing. So for example in one case we know that these kids are making too many cells that produce dopamine and norepinephrine. Dopamine and norepinephrine are these really important neurotransmitters that are important for motivation, attention and pleasure and for some reason these children are making too many of them and they’re turning on the pathways that generate these neurotransmitters in the wrong cells. And so, that…. I mean just knowing that gives you a target- gives you something to target therapeutically.

Dr. Thomas Insel: Is there some way in which having the stem cells the way you describe is going to help us to develop new therapeutics?

Dr. Ricardo Dolmetsch: Oh absolutely. So, so…. this is the thing, right? We need to understand what is going wrong. And things are going wrong at multiple levels. So, so… we know for example.. so the first sort of level of understanding is we have to figure out what the genes are. We’ve started to identify many of the genes. The next level of understanding is we have to understand how those genes are actually changing the function and development of the cells and that is what we are working on-what we have developed. Now, once you know what is wrong with the cells you can then look for ways to reverse that.

Dr. Thomas Insel: I can’t help but ask the question.. how you done this with your own son? Have you taken skin cells and created stem cells from him?

Dr. Ricardo Dolmetsch: We have. And we have sequences genome as well as ours. And you know, I mean, it’s um… it’s a difficult project to have in your own lab. Um… in a way.. you really want to know. And in a way you really wish.. you really hope that what you find is not too terrible. But absolutely, this is one of the motivations- not the only motivation. I think one of the things I’ve discovered in working on autism I’ve met many families – it’s been that it motivates you in a way that… you know… is difficult to explain and in a way I never would have expected when I was being trained as a very basic scientist.

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22 Responses to “Dr. Ricardo Dolmetsch on Autism Spectrum Disorder Research and Stem Cell Possibilities”

  1. don margolis April 25, 2011 at 11:15 #

    The intro to the good doctor’s interview represents the official position of PhRMA on autism rather than anything he himself says. ” No, there is no stem cell therapy for autism at present.”

    This is typical of all mainstream media, following the rules: NEVER TELL THE TRUTH ABOUT EXISTING STEM CELL TREATMENTS, Never mention the dozens of families spreading their good news around the internet. Just keep pushing the pills. After all, 50 years of pill research has produced nothing for autistic children, so a cure is sure to come down the PhRMA pipeline any minute, as all the legal drug-pushers calling themselves doctors will tell you, while they quietly earn their once-illegal commissions from PhRMA.
    Don Margolis, Chairman
    Repair Stem Cell Institute

  2. Sniffer April 25, 2011 at 11:57 #

    Dear Don,

    Superb post .Were behind you and I speak for a lot of people damaged forever by Pharma products.

    God bless

    Sincereley

    Sniffer

  3. Mo Smith April 25, 2011 at 12:18 #

    Don
    Exactly they way we feel.

    Thanks for your support were not the only ones to read this blog that think this way,thank you.

    Mo Smith

  4. Jackie April 25, 2011 at 12:24 #

    I have Asperger’s Syndrome and take Zoloft, which helps me a lot with depression. So Big Pharma isn’t terrible for everyone on the spectrum.

  5. Science Mom April 25, 2011 at 15:18 #

    @ Don, then you will have no problem providing the clinical trials from your stem cell treatments would you? It is so predictable to bleat on about how no one but you tells the “truth”. Tell me then, with published literature; it’s probably worth a Nobel nomination after all.

    • Sullivan April 25, 2011 at 18:30 #

      Science Mom,

      Just in case Don doesn’t return, I checked “clinicaltrials.gov”. I entered
      stem cell autism

      As the search terms. Two hits came up (from the same group, apparently). The hit was not real, it was for the Rossignol group HBOT trial.

  6. brian April 25, 2011 at 15:59 #

    Dolmetsch has successfully generated neurons from stem cells carrying mutations responsible for a particular cardiac polarization defect and for Parkinson’s disease; in each case the phenotype of the resultant derived adult cells cardiomyocytes or neurons) were consistent with the phenotype in the cell donors. A similar approach has been used with Rett syndrome; in Rett syndrome the MECP2 gene is mutated, whereas in autism MECP2 mutations remain a rare cause but the MECP2 gene is aberrently regulated and the amount of the MeCP2 found in most postmortem brains samples from autistic inividuals differs from the results in unaffected controls. Here’s a nice synopsis of that work:

    http://sfari.org/news-and-commentary/open-article/-/asset_publisher/6Tog/content/stem-cell-assay-reveals-early-development-of-rett-neurons

  7. Sniffer April 25, 2011 at 16:49 #

    Dear Science Mom,

    I found thousands.Here are some below .Just great the web these days we soon wont need Pub med,Bmj,Lancet as everyone is doing these days just google and you find a helping cure.

    http://www.stemcells.com/view/0/VirtualIssues.html

    Yours Sincerely

    Sniffer

  8. passionlessDrone April 25, 2011 at 18:03 #

    Hello friends –

    Interesting spin on the stem cell stuff. I love the idea of reverse engineering to learn more, yet I have skepticism.

    The next level of understanding is we have to understand how those genes are actually changing the function and development of the cells and that is what we are working on-what we have developed.

    It seems like the heavy hitters in the genetic realm have largely been identified in autism. There remains the likelyhood of lots of little hitter genes (and other inputs) working in concert to affect change, but it seems to me that at this point, this is wholy different beast to render a model for if our end game is an understanding of lots of different influences exherting small, but real forcse. I guess I’m struggling to see the creation stem cells, and the subsequent modeling of N low penetrance genes, many of which may have developmentally time dependent differences in expression and function, might be performed to give us more insight.

    – pD

    • Sullivan April 25, 2011 at 18:40 #

      “developmentally time dependent differences in expression and function”

      Much better said than my attempt. This is a big question to me.

  9. brian April 25, 2011 at 18:09 #

    Ah, sorry–I mistyped.

    Dolmetsch generated cardiomyocytes from stem with a mutation associated with the polarization defect (Timothy syndrome), rather than neurons, as I mistyped in the first line of my post above, although neurons were indeed generated from PD stem cells; he and others have generated neurons from stem cells prepared from individuals with mutations associated with autism. This autism-in-a-dish approach should provide some interesting clues, such as this suggestion that abnormal levels of functional MeCP2 (here in Rett syndrome, though–I suppose–possibly also in autism) may cause nonheritable de novo mutations in neurons:

    http://www.nature.com/news/2010/101117/full/news.2010.618.html

  10. Science Mom April 25, 2011 at 18:17 #

    I found thousands.Here are some below .Just great the web these days we soon wont need Pub med,Bmj,Lancet as everyone is doing these days just google and you find a helping cure.

    @ Sniffer, it is monkey work to pull a gish gallup of non-relevant stem cell papers. Conspicuously absent are any papers with regards to autism stem cell treatments and non-experimental, i.e. standardised stem cell therapy papers. Now open mouth and insert other foot.

  11. brian April 25, 2011 at 20:23 #

    Sullivan, you and some others might be interested “Annual Research Review: The promise of stem cell research for neuropsychiatric disorders.” The authors begin to address your big question: “Central to the ?eld for neuropsychiatric disorders, recent publications suggest that embryonic stem-cell-based in vitro differentiation models appear to recapitulate the key milestones, leading to a highly coordinated generation of cortex-speci?c orchestras of neuronal cell types.”

    This April 2011 review from a group at Yale is available on-line as free full text at:

    http://onlinelibrary.wiley.com/doi/10.1111/j.1469-7610.2010.02348.x/pdf

    • Sullivan April 26, 2011 at 02:30 #

      Brian,

      Thanks for that link.

  12. Sniffer April 25, 2011 at 20:33 #

    Dear all,

    You hardly try ,this is the easiest web site I found for your perusal.To the right,of the first age real people real resulsts.

    http://www.stemcellschina.com/

    Fairly good considering no high brow scientific study has been done.Pharma`s world just slipping through the sand whilst Wakefield watching.

  13. Sniffer April 25, 2011 at 20:33 #

    Dear all,

    You hardly try ,this is the easiest web site I found for your perusal.To the right,of the first page real people real results.

    http://www.stemcellschina.com/

    Fairly good considering no high brow scientific study has been done.Pharma`s world just slipping through the sand whilst Wakefield watching.

  14. brian April 26, 2011 at 03:51 #

    You’re welcome, Sullivan–I happened to see that just this morning. I should note that sometimes when I post here, the text that appears on the site seems rather wacky; I don’t think that I actually typed “?eld” or cortex-speci?, but I’m glad that you and others are able to get the point. (OTOH, I’m glad that the site now loads much more quickly.)

  15. RAJ April 26, 2011 at 14:24 #

    For those who might be interested, the IMFAR 2011 has finally published its list of abstracts that will be discussed at the May IMFAR 2011 meeting in San Diego. You can look at all the abstracts at the following link:

    http://imfar.confex.com/imfar/2011/webprogram/start.html#srch=words%7Challmayer%7Cmethod%7Cand%7Cpge%7C1

    My interest is in yet another preliminary report from the California Autism Twins Study (CATS), the largest population based twin study ever attempted and they have now found that severity of autism is not inherited and that environmental factors in twins both identical and fraternal may be far more important than classical twin studies have suggested:

    http://imfar.confex.com/imfar/2011/webprogram/Paper8068.html

    “Conclusions: ASD appears to be a discrete clinical entity rather than the tail of a continuous behavior distribution. However, there appears to be a single continuous severity gradient affecting all aspects of behavior characteristic of ASD among affected individuals. Although twins correlate with one another with regards to severity, the correlations are relatively equal in MZ and DZ twins indicating that severity itself is not inherited. Rather, severity is likely due to environmental factors shared by twins. Additionally, MZ twins appear to be more severely affected than DZ twins suggesting that monozygosity may be an environmental risk factor for the development of ASD and its severity”

  16. Clearinfo April 30, 2011 at 22:36 #

    ScienceMom is correct: Don Margolis is a fraud and trolls the blogs. Here is a nice little tidbit about the “Science Advisor” for his scam operation:
    http://sctmonitor.blogspot.com/2011/04/regenocytes-grekos-loses-medical.html

    He tries to hook himself in with valid Adult Stem Cell studies by posting links under his “friends” button on his absurd website. Keep it up Donny boy – The parents of the Duke kids are coming for ya. Even the psycho right wingers keep you at arms length
    because they know you’re a huge liability.

  17. Mrs Eugenia N.T Williams May 30, 2014 at 19:07 #

    Dear Dr Ricardo, I have read about your research, I have a twenty year old son who was said to have a learning disability. A different type of autism. Presently he could not read beyond elementary subjects. He tends to forget what he read

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