Advances presented at the recent Society for Neuroscience meeting

After 5 intensive days at the annual meeting held this year in New Orleans, things are just getting back to normal around here. Among the >28,000 participants, there were several presentations that particularly caught my eye in the areas of autism, schizophrenia and multiple sclerosis.

In the autism realm, Susan Masino of Trinity College in Connecticut tested the effects of the ketogenic diet (KD) on a mouse model with autistic features, the BTBR strain. This diet is a high fat, low carbohydrate regimen that has proven quite useful in treating pediatric and drug-resistant epilepsy. Since ~1/3 of autism spectrum disorder (ASD) children have seizures, it is logical to test this diet on the BTBR mice. Five week-old mice were fed a control or a KD for 3-5 weeks and then tested for several ASD-relevant behaviors. Those on the KD displayed improved social interaction behaviors and fewer repetitive behaviors. This diet did not have a detectable effect on these behaviors in a standard lab mouse strain (C57Bl/6). The authors concluded, “We suggest that the KD be considered as a treatment opportunity for autism, particularly in cases with comorbid epilepsy in which the diet could have a dual benefit of reducing seizures and improving symptoms of autism.”

M.R. Pitcher, J.L. Neul and colleagues at Baylor College of Medicine tested a new formulation of insulin-like growth factor 1 (IGF1) in a mutant Mecp2 mouse model of Rett syndrome. Mutations in Mecp2 cause Rett. Recall from my book and from prior posts here that a small IGF1 peptide has very positive effects on Rett symptoms in a mutant Mecp2 mouse model, and that this led to the current clinical trials of IGF1 in human Rett patients. These trials use the full length, complete IGF1 rather than the smaller, truncated form that was used in the mice. This is because the latter form is not yet approved by the FDA while the full length form was already approved for treatment of short stature and is believed to be safe. In the work by Pitcher, a new formulation was tested, which is more stable and would therefore require less frequent injections. Unfortunately, a low dose of this drug had no effect on symptoms in the mice, while a high dose had detrimental effects, including a significant decrement in survival time. Meanwhile, the group of Mrganka Sur at MIT reported that treatment of Mecp2 mutant mice with the full length version of IGF1 was less effective than the short version. These new results are cause for worry about the outcome of the clinical trials of the full length form of IGF1.

On the schizophrenia front, certain variants of the gene neuregulin (NRG1) have been linked to increased risk for schiz. D. Yin and colleagues at the Georgia Health Sciences University reported on a new mouse strain in which NRG1 can be experimentally controlled, specifically in certain neurons in the brain (pyramidal neurons in the forebrain). They find that turning up NRG1 levels in these cells during development results in adults with hyperactivity, impaired memory and decreased prepulse inhibition (relevant for schiz and autism). Importantly, turning down NRG1 in the mice that already display these symptoms causes the symptoms to recede. In the converse experiment, they turned up the level of NRG1 in adult mice and found that the schiz-like symptoms could be induced. These results suggest at least two intriguing conclusions: First, the level of NRG1 in specifically in pyramidal neurons can control behavior, and second, the adult brain is plastic and can respond to modifications in NRG1 with significant changes in behavior. As I pointed out in my book, and in past posts here, similar findings of adult brain plasticity have been made in mouse models of Rett syndrome, tuberous sclerosis and fragile X syndrome. All of these findings offer reasons for optimism for ameliorating symptoms in patients.

P.M. Grace of the group of Linda Watkins and Steve Maier at the University of Colorado at Boulder reported a very promising approach to treating multiple sclerosis. Using a rat EAE (experimental autoimmune encephalomyelitis) model, they tested the anti-inflammatory cytokine IL-10 by encapsulating its gene in slow-release microparticles that gradually degrade after injection intrathecally (similar to spinal tap injection). This approach would presumably allow a long-lasting increase in IL-10 levels in the spinal cord and possibly in the brain. When this drug formulation was injected at the time of onset of behavioral symptoms, it increased voluntary exercise (wheel running) and social exploration, and decreased debilitating motor symptoms and pain sensitivity. Most striking was the effect of IL-10 on survival: at the time when 40% of the EAE rats had prematurely died, the IL-10-treated EAE rats were all alive. Clearly, this drug formulation merits further exploration.

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7 Responses to Advances presented at the recent Society for Neuroscience meeting

  1. Inasy says:

    Dear Dr. Patterson, I just started my 15 year old epileptic/ autistic son on the ketogenic diet. He has been in ketosis for a week as the strip tests indicate. And a few days in, he developed a fever and a runny nose with cough. he is also relatively calm, and is typically very hyper/agitated. my son has NEVER developed a fever, or been ill before, with the exception of one ear infection which was also triggered by a modification to a low carb diet. Ketosis seems to agree with him. Is this recent illness something I should celebrate? Or is it just a coincidence? What could possibly be at play here between diet and the fever. I am convinced that they are related. No one else is currently ill in my household. And my son has never even sufferered a common runny nose in his life, let alone a fever.

    • phpatterson says:

      That sounds v interesting Inasy. I’m not aware of connections between this diet and fever or infection, but I have two ketogenic diet reviews on my desk that I have to read for a lecture tomorrow. Perhaps I’ll find something of interest. Autism symptom relief during fever has been noted in a small study by Andy Zimmerman, as noted in my book. Cheers, PHP

  2. Ketogenic diet eh? Another feather in the cap of the cannibal hypothesis of autism! 🙂

  3. Melanie Ciccone says:

    dear php,

    glad to read more deep science is looking to our diet for health solutions. Hippocrates knew a thing or two…wonder if you are familiar with the work of Dr. Natasha Campbell-McBride/GAPS diet (Gut and Psychology Syndrome) -http://gapsdiet.com/GAPS_Outline.html? Her general thesis is that a compromised intestinal barrier, damaged mucosal GI lining can lead to what you might refer to as “Infectious behavior” in addition to playing a role in autoimmunity (including food allergies, asthma, IBS, IBD- the whole enchilada of GI systems’ problems), as well as Autistic Spectrum ADD/ADHD, epilepsy, in some cases Schizophrenia, etc. Along with a destructive Human-Biome playing an equally critical role in these conditions. The GAPS protocol is: 1) heal and seal the gut lining with a therapeutic diet and, 2) reestablish a healthy diverse microbiome both with therapeutic strength probiotics and fermented foods (anti-microbial remedies, be they pharmaceutical or nutraceutical if called for).

    After reading the current New Yorker article “Germs R Us” (Oct 22, 2012) by Michael Specter, on the heals Scientific American artical “The Ultimate Social Network” citing the important work of your Cal Tech college, Sarkis with bacteria and inflammatory molecules, AND, the recent NY Times piece -we corresponded about earlier – Immune Dysregulation it is all starting to come into focus. What an exciting time to be in any of these fields!!!! To my mind, Dr. Natasha’s approach puts it all together in a do it yourself nutritional approach if you do not/cannot get medical help.

    It appears she has had tremendous success with 100’s of her patients, and people following this diet from every corner of the globe. Having an MD, and an MS in both neurology and nutrition she has a cultivated a very particular lens from which to practice. The diet is a long term commitment (approx. 1-2 yrs). However, with the right incentive, be it a sick child or a 40+ year journey of health problems, it seems like a small price to pay if one can actually significantly reduce and or abate these plaguing issues.

    Biochemist A. Beauchamp illuminated the critical nature of ones internal environment relative to our health and the ability of our body systems to function properly; Pasteur/Koch helped to underscore the significant role pathogens play in disease; At some level we seem to understand that you are what you eat and what you absorb; Factor in genetics/epigentic effects, and the fundamentally pivotal role bacteria wield in our internal and external environments and we may finally be holding all the pieces to the puzzle. N’est pas?

    [To your reader above, Inasy, Dr. Natasha specifically talks about fever relative diet and ketosis. She writes about it in her book, Gut and Psychology Syndrome. ]

    melanie in south pasadena

    • phpatterson says:

      Thx v much for this info Melanie. I’d be interested in what you found out about fever and keto diet as I doubt I’ll get to that book. Cheers, PHP

    • Inasy says:

      Thank You Melanie. We are kindred spirits, for I too am a big fan of Dr. Campbell’s work and now Dr. Patterson’s. My boys have been on the GAPS diet for four years, and it has made a remarkable diffference for my youngest now age 11. My oldest however had epilepsy and sub clinical seizures seemed to have been causing some damage. I consult with Dr. Campbell and it was she who initially recommended that I treat him as an epileptic patient and keep him on stage two of the GAPS DIET- which is essentially Ketogenic. I have her book, but I am not sure where she referenced fevers in connection with ketosis. I will revisit that ASAP. thanks again

  4. Melanie Ciccone says:

    Inasy, so glad to stumble upon you here on PHP’s Infectious Behavior blog. Moreover, what an affirmation to read that you are now in year four of GAPS with your child/ren. It makes so much sense. How very heroic – although I suspect you dont view it that way. I cannot place where I read the connection of fever and ketosis specifically (having poured through her book, online articles, and FAQ’s all in the last week). The 2010 printing of her book has an entire chapter dedicated to Epilepsy. No doubt you have imagined emailing directly. Should I find the location I will post it is possible I conflated them given that she discusses fever/infection fighting as well as ketosis diet and epilespy.

    My very best to you and your boys.

    Gratitude to the scientists!!!!

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