The Magnetic Resonant Therapy (MRT™) Autism Research Study Finishes Today: The Results Are Remarkable.

I had the privilege of serving as the principal investigator or PI for the double-blind, sham-controlled investigation of the effects of a special form of transcranial magnetic stimulation therapy as an intervention for autism. [ClinicalTrials.gov Identifier:NCT01985308].  I started collaborating up with Prof. Jin and the BTC in California about a year and half ago after MRT had already shown positive effects in several of my patients. I want to thank all the families for their dedication and efforts in helping this most important research project. Without them, none of this would have been possible. The study was financed by the Newport Brain Research Laboratory. 

Professor Yi Jin of the Newport Brain Research Laboratory and the Brain Treatment Center in Newport Beach, California, developed a different theory about the way the brain functions and how it uses harmonic energy to synchronize its communications. That led him to develop a new system of transcranial magnetic stimulation now known as MRT™.

Dr. Yi Jin presented the preliminary results of the study at the Autism One Keynote address in May 2014.  At that time we all were still blinded and did not know which patients comprised the curves in the graphic below.  I served as one of the raters and Dr Toni Jin was another rater of the outcomes.  She and I were always very close with our independent assessments which is reassuring that the effects observed are both consistent and real.  A link to more of Dr Jin’s Autism One presentation is here. The link will further describe the study design. http://braintreatmentcenter.com/pdf/052614_PR_MRT001_GRAPHS.pdf

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The graphs illustrate the difference in effect in the sham versus treatment group in the first 5 weeks of treatment, and also show the similar response to treatment once the sham group initiated treatment after 5 weeks.  The orange line represents the average outcomes from the group of children starting with sham treatment – at 5 weeks they moved into regular MRT daily treatments. The likely reason for the subtle downtrend in the sham group is the conditioning of the children to daily life in the center. The blue line represents the group of children starting with and continuing with treatment.  That group received a total of 10 weeks of treatment. The composition of the groups includes the data from the ~20% of children in either group who failed to respond to therapy. The work continues so we can find ways to reach the 20% non-responder group of children. Both myself and Dr. Toni Jin, despite being blinded to the sham versus treatment status of the children, were able to reliably detect the effect of MRT. More about the special magnetic coil used in the study a little later in this blog. But first what the experts think about this work. 

WHAT NEUROSURGEONS ARE SAYING ABOUT MRT

“What the Brain Treatment Center has done is revolutionary. Using evidence- based principles with TMS, they have created a delivery system that customizes treatment based on the patient’s own QEEG. Addressing the core frequency mismatch that occurs in various parts of the brain, and not the patient’s symptoms per se, allows this system to be potentially useful in numerous psychological and neurological disorders, from autism to Alzheimer’s.” Dr. Kevin T. Murphy, Associate Professor and Vice Chair of the Department of Radiation Medicine and Applied Sciences, UC San Diego Medical Center.

This noninvasive, personalized form of neuromodulation is very patient specific, and has far-reaching clinical implications”. Dr. Charles Liu, Professor of Neurological Surgery, Neurology, and Biomedical Engineering and Director of the University of Southern California Center for Neurorestoration, Los Angeles, California.

COMMENTS FROM PROFESSOR YI JIN ABOUT THE MRT AUTISM STUDY

80% of the kids in the study had huge improvements (30% reduction in Autism symptoms measured by Childhood Autism Rating Scale) and 40% are neurotypical by CARS in just 10 Weeks of MRT.  We understand this is a relatively small (N =28) study which cannot be generalized to apply to the entire population of Autism.   These findings, however, very closely resembled our clinical data of over 700 cases treated at our centers from 2005 to present.  Both UCSD and Rady Children’s Hospital are aware of our MRT-001 study results and have just been approved for a large (N=400)  MRT-003 double-blind study to validate our preliminary findings.  We know this is limited but we believe this is a very important beginning of a novel treatment for Autism.

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http://www.braintreatmentcenter.com/staff [either click on the link or paste it into your browser to see Dr. Jin’s Autism One presentation]

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Dr. Bradstreet present recent neuroscience advances at Autism One in Chicago in May 2014.

WHAT A MOTHER OF THREE CHILDREN WITH AUTISM THINKS ABOUT THE MRT STUDY AT BTC ATLANTA

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I have had the pleasure of working with the mother of 3 children with moderate to severe autism for a few years now. Ashley, an Audiologist, has twin girls born at around 25 weeks (very premature) and a younger boy born at 35 weeks.  All three have been diagnosed with Autism and all three participated in the study at BTC Atlanta.  She has worked for years restoring her kids with diet and trying to heal the GI tract with various interventions. All of that helped as a basis what came next – MRT. A link to her interview is on Vimeo at http://vimeo.com/97462194 . (either clink on the link or paste it into you browser).

Kara with Study Coil

Kara at the BTC Atlanta Center with the unique study coil and MRT technology. The coil was designed to reproduce the clicking sound of the magnet without actually creating any magnetic discharge.  A computer remotely controlled the study based on a randomly assigned and coded patient number.  Even the treating tech could not tell which arm of the study was being used for a given child. After 5 weeks all children were receiving MRT. This was the open phase of the research.

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Dr. Bradstreet with MRT study staff: Jijeong (from the Newport Beach BTC office), Beth and Kara (from BTC Atlanta) – our team all had a chance to celebrate the success of the study. Other BTC- CA staff helping on the study and not pictured here were Carlos, Christine, and Kevin and Kim – thanks to all of them.  Alex at the BTC in California stayed behind the scenes with Dr. Bob Silvetz – both of whom were instrumental in the study.

Toni Jin Study

We are all indebted to Dr. Toni Jin – MRT Study Research Coordinator, put in long hours to make sure all the details were properly recorded.

If you are interested in learning more about MRT you may contact the BTC office in Newport Beach – Phone: (949) 851-3086.

The BTC- Atlanta office is located in the Northeast Atlanta metropolitan area near the Mall of Georgia:  4486 Commerce Dr, Suite B, Buford, GA 30518. The phone for that center is 678-765-8427.

Dr. Bradstreet’s medical practice is located in the adjacent building and may be contacted at 678-288-9222.

 

 

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Prelude to my upcoming Autism One lecture on the INCREDIBLY important ENDOCANNABINOID SYSTEM

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Teri from Autism One Radio interviews Dr Bradstreet about the Autism Nexus.  Listen here by clicking on the link below.

http://podbay.fm/show/324695865/e/1395375892?autostart=1

See you at Autism One in Chicago.

In Defense of 23andMe.com – why knowing your genome is important

Up until November of 2013 the controversial 23andM.com website offered people the opportunity to get genomic insights to their past and their possible future – at least their future vulnerabilities.  After 2 years of back and forth communication wherein it seems 23andMe was trying (unsuccessfully) to convince the FDA that people had the right to genomic information the FDA issued a cease and desist order and now 23andMe states this on their homepage: “23andMe provides ancestry-related genetic reports and uninterpreted raw genetic data. We no longer offer our health-related genetic reports.” 

The price of the testing dropped dramatically and is now only $99 for a salivary genomic test.  The problem is that unless you actually care what percentage of your ancestral DNA comes from what continent or how much residual Neanderthal your parents contributed to you, the raw data is merely a huge outpouring of A,T,C G data (nucleic acid pairs) which even a competent geneticist would find daunting without the aid of serious computer databases.  But therein lies its wonder – we do have access to amazing databases which offer us glimpses into the rapidly expanding arena of medical genomics and personalized health care. 

Enter in a support industry growing up around 23andMe like livewello, which offers an app for downloading all those ATCG codes and converting them to more easily understood labels, like MTHFR – a gene with common single nucleotide substitutions which may result in dramatic reductions in its enzyme’s ability to methylate folate (a completely treatable genetic risk factor for heart disease, certain cancers and autism). 

 

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The livewello gene app for 23andMe only costs $15 and equally they do not provide you with any specific health recommendations or interpretations.  But they do add a filter which makes it easier to identify the genes on the OMIM website.  OMIM is part of the the US National Library of Medicine and it is an invaluable tool. 

However, there is a catch. 23andMe and livewello (or any of the other gene apps) only identify SNPs and do not adequately look at copy variances and deletions. Still there is useful information, which in knowledgeable hands can give helpful information.

In the near future, (like after Autism One and IMFAR) I will write up an interpretation guide for the primary genes I find helpful and with that I hope to further all of our understanding of the emerging field of personal genomics.  Remember – knowledge is power – what you do with that power can change your life in important ways through the use of informed choices. 

Clinical Trial on the Use of a Unique Form of Transcranial Magnetic Stimulation – MRT for the Treatment of Autism is Nearing Completion – Results to be Presented at Autism One 2014 in Chicago.

Clinical trial NCT01985308 (details available at www.clinicaltrials.gov) or directly at http://www.clinicaltrials.gov/ct2/show/NCT01985308?term=bradstreet&rank=1 is in its final stages of completion.  The preliminary results of the study will be presented during the Autism One conference upcoming in Chicago in May ( http://www.autismone.org/content/2014-autismone-conference ). MRT uses powerful magnetic pulses to stimulate the brain is unique ways.  The outcomes from the early use of MRTwere recently presented by Prof. Yi Jin, the developer of this type of therapy at the annual AANS meeting.

 

I’ve had the pleasure of working the Brain Treatment Center team including various technicians Prof Jin and his sister Dr. Toni JIn for the past several months on this project. The study has been arduous and Toni has put in some amazingly long hours to help the parents, the children and me with this complex area of research.

The study recruited 28 subjects with autism ages 4-12 and entered them into a 12 week program.  The treatment required frequent EEG testing and examinations. The magnetic (MRT) portion was based on the EEG findings and uniquely tailored for each patient by the assessments of individuals neurophysics (electronic signature of the brain).  The study had/has two arms with each group being randomly assigned to either 5 weeks of sham and then 5 weeks of treatment and the other group getting 10 continuous weeks of treatment. Everyone remained blinded and the seal on the numerical codes will not be broken until the end of the study.

I hope you join Drs Jin and myself at Autism One for a look at the use of MRT for autism.  For more information about MRT you may visit http://vimeo.com/braintreatmentcenter/videos and if this is something you feel may apply to your child you may contact my office for a consultation.  MRT, a form of TMS, is only available by prescription and requires the supervision of a physician. The FDA has approved TMS for the treatment of refractory depression. It is not approved for the treatment of other disorders including autism and its use is considered an off-label application of the technology which is permitted in the US. Additional research is expected to start in the next 12 months at UCSD regarding its use in autism.

International Interest in Stem Cell Therapies for Autism Continues to Grow Amidst Ongoing Controversies

I am pleased to announce today’s publication in the World Journal of Stem Cells of our review of Mesenchymal Stem Cells (MSCs) for the treatment of autism.  Our team representing Italy, the US and Ukraine, reviewed the evidence and present understandings of this important class of stem cells and what we know about its potential and rationale for autism therapeutics. We also discuss various struggles, including regulatory restrictions in various countries, for the present application of the MSCs to autism treatment. Here in the US I routinely extract adipose derived stems cells (mostly MSCs) for the treatment of arthritis – primarily knee joint degenerative disease. This is a relatively simple application of stem cell therapeutics and I am about to publish our initial outcomes from this.  I DO NOT HOWEVER TREAT AUTISM WITH STEM CELLS HERE IN THE US. I use EmCell in Ukraine for advanced autism related cell interventions.  Together with the EmCell team, I have submitted our outcomes in the autism population for publication and it should be available soon in print. If after reading this article – via the link below – you are interested in stem cell therapies, you may contact my office to set a time for consultation.

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The Link to the Public and Freely available article is here: http://www.wjgnet.com/1948-0210/pdf/v6/i2/173.pdf

The Autism Nexus: New Discovery of a Link Between the Gut Microbiome, the Immune System, Brain Dysfunction and Vitamin D and Vitamin D Binding Protein (GcMAF)

I am very proud of our recent work published in the highly regarded Journal of Inflammation.  http://www.jneuroinflammation.com/content/11/1/78  By clicking on the hyperlink you browser should take you straight to the article which is available for no cost at the journal’s website. Once you are there click on the pdf button (the yellow arrow shows you where to click once you get to the article on the web).  Before you jump to article page let me explain in easier language why this article is so important. It is the first article any of us as authors have written that was accepted without any critique or changes, which means the reviewers thought very highly of it. While that is important, it is only part of the significance of our findings.  It has always bothered me that minor changes on the gut bacteria and yeast (microbiome) could result in wild and crazy changes in a child’s behaviors. While that observation is common among those of us treating the biology of autism, it was actually very difficult to understand mechanistically at the level of the child’s biology, at least until now.

We believe we have uncovered the nexus (intersection) of the observations regarding Vitamin D deficiency, GcMAF observed improvements in behavior, see: http://www.la-press.com/initial-observations-of-elevated-alpha-n-acetylgalactosaminidase-activ-article-a3450 , immune dysregulation, brain inflammatory changes (mostly in microglial regulation), and the microbiome.  Briefly, the endocannabinoid system is part of the cell systems that regulate the immune system and the brain. In particular, it seems the CB2R (cannabinoid 2 receptor) reads the background environment of the individual (diet, microbiome, etc) and sets the tone of the immune defenses.  Last year we published the first observations of CB2 dysfunction in autism (J Autism Dev Disord. 2013 Nov;43(11):2686-95. doi: 10.1007/s10803-013-1824-9.). With this follow on work it seems likely that the endocannabinoid system is at the center of the complex biomedical disruptions underpinning the autism epidemic we are observing.  Now for your homework. Go the Journal of Neuroinflammation website and get the entire article. After you read it you can ask you questions. (use the link provided in the first paragraph).

 

JNI Article facepage

CDC data show continued rise in autism spectrum prevalence for Autism Awareness month

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You can download the entire article and go over the statistics for yourself but here are a few of the outstanding observations these data offer us.

1) The ADDM site prevalence has risen to 2.38% of boys and 0.5% of girls, although in figure 4 of the report it goes as high as 2.75% of boys.

2) The median age of diagnosis of autism was 53 months (4 years 5 months).

3) The disorder is diagnosed more frequently in the white non-Hispanic population

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You won’t be able to read this chart on your mobile phone very easily, but the data are certainly terrible for our children.

As a background in statistics, 10 case per 1000 in prevalence equals 1%, so the prevalence for both boys and girls combined in the sum of the ADDM areas was: White non-Hispanic 1.58%, Black 1.23%, Asian 1.23%, Hispanic 1.08%.  The overall ratio of boys to girls was 4.76 to 1.

Based on the available scientific literature it is difficult to explain the nearly 5 fold increased risk of ASD observed in the make population. The simplistic observation would be to look at the Y (male) and X (female) chromosomes and see what is happening there.  Very few autism risk factor genes have been identified on either chromosome apart from fragile X which accounts for only a small percentage of ASD cases. This implies some epigenetic (gene-environment) interaction wherein males show more vulnerability than the females. Finding these factors has been elusive, but a new study may give us some clues.

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The American Journal of Human Genetics. 94, 415–425, March 6, 2014

This is a complex study, but the apparent observation is that females have significantly higher numbers of small copy-number variants (CNVs) in the DNA (more mutations) but have less risk of autism – meaning being female somehow lends protection to the gene variations and implies males are more sensitive to genetic variations.  As with previous studies these factors are NOT occurring on the sex chromosomes, but rather on the other chromosomes.  They also observed higher levels of neurodevelopmental risk factor genes in the mothers compared to the fathers of the children with ASD, which was again consistent with the view that females tolerate a higher burden of CNVs than males.

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The odds ratio of having a neurodevelopmental associated gene CNV was 3 times higher for females than males (15% compared to 5%). However, only 308 of 4482 males (6.87%) tested in this study actually had CNVs detected.  So even this study fails to explain on a genetic basis the genetic risks of autism for the majority of cases.

This leaves us still searching for the combination of genes and environmental factors triggering this incredible and frightening rise in ASD observed in the most recent CDC study. I will be presenting more on this at Autism One in Chicago this year.

Autism Says Goodbye to 2013 and Hello to 2014: Breakthroughs and Progress

As it ended, 2013 turned out much better than I expected. I received a special present on Christmas Eve when, Itai Berger, Editor of Frontiers in Human Neuroscience, emailed me that my article on transcranial ultrasonography had been accepted and was available online in provisional format.  See abstract below.

Frontiers Abstract

This publication was the result of ongoing collaborations with my Italian colleagues at the University of Firenze (Florence). Professors Ruggiero and Pacini are pushing the immunological research in autism, chronic fatigue syndrome (ME/CFS), and cancer through their detailed laboratory investigations of the vitamin D binding protein – GcMAF. It was our shared interest in GcMAF that brought us together on the ultrasound research.  2012 ended with the publication of the first article describing Nagalase and GcMAF in ASD. (title below).

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One year later – to the day and after more than 10,000 article views – I was lecturing in Dubai at the 2nd International Conference on GcMAF Immunology.  The conference was well attended with physicians and researchers fro many countries. Pediatricians and Psychiatrists from Dubai, Jordan, Turkey, Italy, India and the US shared their experiences with GcMAF therapy in ASD.  It was very rewarding to hear their stories. They presented videos and collections of cases, all of which observed something similar to what i had already published: most children with autism respond vigorously to GcMAF and side-effects were minor and transient.

gcmaf conf dubai

I consult with families from 37 different countries around the globe and I hear the same stories about GcMAF regardless of the child’s ethnicity or culture. That likely speaks to the immunological ties between immune dysfunction and autism.  Below is one of the many extraordinary letters I received late in 2013.

Once upon a time my first born son was autistic.

       He stopped developing properly around the age of 1 and lost the few words and skills he previously had, though I don’t believe he was up to par even then. From there he slipped away from us into his own world and it was as if he couldn’t even see or hear us. He didn’t know he had a name, that we had names, or that we were even there. He didn’t babble, he didn’t play with toys, he didn’t even look up at people when they entered the room. When we had kids over to play he would hide in a corner and cry. He was chronically ill with one sickness after another, always tired, sleeping 14 hours at night and if we woke him up from his nap before 3 hours he would scream hysterically sometimes for 2 hours. The first doctor told me he was just a boy and boys develop slower, the second doc said we were just bad parents, and the third finally gave us a diagnosis at 27 months – 8 months after I had begun to worry.

     We tried everything; B-12 shots, ABA 20 hrs. a week, speech, OT, vitamin D, probiotics, and an extremely strict diet of no gluten, dairy, eggs, nuts, soy, fish, dyes, preservatives or anything artificial. These things did help a lot but even so it was an extremely difficult uphill battle of working months to gain a skill and if one person wasn’t consistent on the implantation of a goal he would regress immediately. There was a whole year that he woke up screaming every night for hours. Nothing I did helped and he couldn’t tell me what was wrong so I would resort to laying beside him and crying myself. He would wake up his baby brother who then also began screaming. It was a long year of screaming even from me! I once responded to one of his fits by having an all out screaming meltdown of my own, face down on the floor pounding the ground like a 2 year old. I was depressed, exhausted, and contemplated many times just ending it all…I have to be real because other parents need to know they are not alone in this. Besides the screaming he was always horribly constipated to the point of needing medical intervention, he had raging eczema head to toe, was allergic to literally everything; I knew my son was sick. I often told my husband, “some day 50 years from now the doctors will finally figure out that autism is a problem with the immune system but by then it will be too late for him.” I thought he would live with us his whole life and just continue to be a tired, sick, crying, itchy boy, who couldn’t get words out or look at us. Then my friend told me she found a doctor named Bradstreet who did believe it was immune related and was treating it! I had hope!          

     We started GCMAF and began seeing real progress after the level 7 dose. He seemed more energetic, cried less, and speech and eye contact were improving. Each week began to be amazingly better than the last and it felt like we were seeing actual recovery. Then after about a month he ended up in the hospital with a raging sinus infection of strep that led to an abscess behind his eye. This is a very rare complication but as I said, he had the immune system of a flea. He needed emergency surgery to save his eye but continued to battle the infection and a fever of 104 for 11 days until they resorted to surgery again, this time fully removing his right ethmoid sinus.  During his hospital stay and for 3 weeks after while he was still on antibiotics we couldn’t do GCMAF. His regression was significant. His speech went way back to about 9 months before we started GCMAF, he could only get a few words out at a time with great difficulty and even I couldn’t tell what he meant. He actually said to me finally, “mommy. help me,” and I said, “with what baby?” He struggled to get out the following, “with the…words…not come….out… good.” I cried because I knew he felt trapped in his own body unable to do what he was trying to. When I told him the shots were going to help him be able to speak he was eager to get them and reminded me every week on Wednesdays.

     When we started back up again and finally got the progress going he developed a rash which I now know was molluscum but at the time thought it could be related to GCMAF. We changed his dose from the level 12 once a week to level 5 twice a week and then we lost him. He went off into “autism-land” as I call it. Didn’t hear us, couldn’t focus, couldn’t even accomplish a single step direction and wandered around aimlessly. This dosage was working for other kids but not for him. We went back to level 12’s once a week and after 6 weeks of that he was in everyone’s mind effectively cured.

     His speech and OT discharged him, and after 2 weeks of being in a typical kindergarten class with no aid, the school coordinator told me he didn’t even need any special accommodations. We increased his school day to be full day now from 8:30-3:30 and even though he isn’t even 5 yet, there are zero problems. Zero. No fits, no meltdowns, no non-compliance. His teacher told me he listens in class, follows the schedule with no extra prompting, plays with kids on the playground, holds his pencil properly (big one!), and even sits with friends asking them where they live and what they ate for snack. After school he is able to tell me what he did, describe details about movies or books they read, sing me songs he learned, and he still has energy to play and doesn’t melt down when we get home. He never previously had the skills of recalling events or asking/answering questions properly until this. He currently has no therapy and we see no autism in him whatsoever. He says what he wants when he wants fluently, uses slang terms and laughs at jokes! He has even developed a little bratty back-sass attitude which my husband and I correct but then turn to each other and cry happy tears because it’s SO normal!! He was actually able to tell me that he likes the shots because his sleep is better, he has more energy, and he can speak better. He also hasn’t gotten sick once since the hospital stay back in March. His bowels are no longer dependent on laxatives daily as they were for 2 years. It’s like a dark cloud has been lifted and my son has been freed from his internal prison. We have the son we never had but knew was in there somewhere dying to get out. I have no doubt he will live a normal life and accomplish anything he wants to from now on. I don’t know if he will need GCMAF permanently or not but even if he does I don’t care. I will never let him go back into that cave. I firmly believe God answered my prayers and healed my son and he used Dr. Bradstreet and GCMAF to do it. Our son is healed and so is our family.

Forever indebted and grateful beyond measure,

His Mom

As a parent (and I am one with 2 boys, my own son and my step-son are both on the autism spectrum) these stories are powerful and touching.  But as a scientist I am driven to understand the mechanisms behind these types of anecdotes. The story relates a child rapidly changing state from significant and non-verbal autism, to observed to be normal by parents, teachers and therapist over a mere few weeks.  Autism has been felt to be a developmental and irreversible brain disorder. Clearly that is not always the case, as many stories of recovery are being published in the lay literature.

So how can this happen?  Mechanistically, I think this must represent the presence of an interfering inhibitor to normal neurological functioning. Whatever this substance or effect is, it acts very much like local anesthesia blocking signals in specific parts of the brain. In at least the example described above, that effect is then rapidly dissipated and the brain essentially wakes up. This story is common and doctors at the conference in Dubai presented their own versions describing very similar events in their practices as well. But not all children respond to GcMAF and that speaks to various subtypes of the disorder, some of which are readily recovered while others seem much more entrenched in whatever autism represents at the brain level.

It appears a significant subset of autism is immunological driven and that would fit the observations noted from around the world regarding GcMAF as a therapy. The graphic below is from a review article: Gesundheit B, Rosenzweig JP, Naor D, Lerer B, Zachor DA, Procházka V, Melamed M, Kristt DA, Steinberg A, Shulman C, Hwang P, Koren G, Walfisch A, Passweg JR, Snowden JA, Tamouza R, Leboyer M, Farge-Bancel D, Ashwood P. Immunological and autoimmune considerations of Autism Spectrum Disorders. J Autoimmun. 2013 Aug;44:1-7. doi: 10.1016/j.jaut.2013.05.005. Epub 2013 Jul 15.

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IN the graphic the authors depict the maternal immune system with its macrophages and other immune cells priming the response of microglial cells in the fetus.  Microglial cells are derived from macrophages which migrate into the brain during fetal development.  Those macrophages then undergo changes to become microglial cells.  They, however, maintain many of the features of their original macrophage immunochemistry. Missing from the diagram is another intersect circle representing the postnatal environmental effects. But regardless of that limitation in the representation, the hypothesis they propose is chronic immune – inflammatory changes in the brain secondary to microglial swelling.

GcMAF as noted in my paper, stands for Gc protein macrophage activating factor.  That name makes it sound like a pro-inflammatory molecule and as such based on the model above it would seem to be the last thing you would want to give to a child with autism.  As it turns out, the argument for chronic inflammation in the brain of children with autism is not universally agreed upon and other researchers, particularly Prof Manuel Casanova, have the opinion there is no inflammation in the autism brain.

I had the pleasure of sitting with Prof Casanova at several autism-related think tanks where the immune system was being discussed.  He took a decidedly differing view that there was no evidence of inflammation in the autism brain, but rather there was abnormal construction of the brain’s special electronics and at its smallest unit the minicolumn.  Casanova explained he had dissected scores of brains in great detail and inflammation was not present.  Instead the consistent finding was abnormal minicolumn construction. Below is an excerpt from a complex but insightful review we must consider.

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How is it that both camps: the inflammatory and the minicolumn, can be so divided in their views of autism?  First, I agree that autism is primarily influenced by epigenetic factors. In 2013 I participated in a review of these factors which is public access.

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In this review we wrote: “The term epigenetics was first coined in the 1940s by British embryologist and geneticist Conrad Waddington, who described it as: “the interactions of genes with their environment, which bring the phenotype into being” [17]. Our present knowledge enhances this earlier understanding, and epigenetics now evaluates the alteration of DNA transcription via variations in DNA methylation and histone modifications, but without alterations in the DNA sequence. These variants represent the epigenome, which in turn will be reflected in the transcriptome: that portion of the DNA which is being actively transcribed into RNA.”  The key is the environment regulates DNA transcription (messaging) without changing the sequence (no mutations) of the DNA.

Let’s return to the original article I posted on Transcranial Ultrasonography of the Brain.  An important part of that research was the publication of this research in Brain:image

And most importantly this observation; that there was too much fluid around the brain of children with autism.

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In the figure above I excerpted the images from Shen, et al., 2013 and added the arrows and notations of increased EAF.

In our paper on TUS we observed the same effect – increased fluid surrounding the brain. Below is a side-by-side comparison of fraternal twins from our paper in Frontiers in Human Neuroscience (2014).

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Under normal conditions the fluid (hydrostatic) pressure of the subarachnoid space (the fluid surrounding the brain) is not sufficient to keep the space fully open at the point where the brain folds itself closely to the skull.  In figure 13 from our paper, you can see the space of Twin A stays constant at 0.16 cm as the underlying brain compresses the arachnoid (meninges) of the brain, whereas with Twin B the space is compressed down to 0.01 cm. Now go back to the images from the Brain study of Shen, et al., 2013. If you study those images you will see that in the neurotypical child, the gyral summits (places where the brain folds up towards the overlying inside of the skull) come is very close proximity to the inner lining of the meninges and typically seem to be touching the membrane.  In our higher magnification views we see the same effect (Twin B). However, we and Shen, et al., 2013 observe the same increased distance of fluid volume in the case of autism.

So what does this mean?  At a recent MAPS conference I pulled Professor Theoharides aside to discuss my observations.  “Theo”, as well al call him, is a brilliant Mast Cell researcher and you can pull up his publications at his website: www.mastcellmaster.com.  I will insert a portion of one article, but realize Theo has extensively published on the immune and mast cell effects in ASD.

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The graphic below is in my opinion a more complete understanding of the immune and epigenetic effects than the one from Geshundheit, et al., 2013.

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This graphic gets us closer to what I think is really happening in autism, but it leaves out the potential role of the very much neglected meninges in the development of autism. Theo agreed this was an intriguing notion and one of my projects is to finish a review of this factor with Theo in early 2014. What I now theorize happens in autism is somewhat like happens in experimental models of multiple sclerosis – although obviously different in timing and specificity.

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The meninges make the EAF which fills the subarachnoid space – that same EAF and subarachnoid space which is observed to be increased both both us, Bradstreet, et al., (2104), and Shen, et al., (2013).  In the research above, the inflammatory changes in the subarachnoid space, what both Shen, et al., 2013 and we think is is happening, induce changes in the microglial cells of the cortex making them more appear more inflammatory and less ramified (supportive).

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The cells are noted to be round and this is the way they look when they are inflammed.

In direct distinction, GcMAF treated microglial cells convert to the supportive ramified state. This means that the effect of GcMAF on microglial cells and macrophages is NOT inflammatory, but the opposite – anti-inflammatory.

In findings soon to be published, the images dramatic support this effect. I believe the shifting of macrophages and glial cells to anti-inflammatory states can explain why and how the mother’s story of her son’s recovery happened. To more fully understand this we need to understand the birectional role of TNF-alpha on memory and brain development.

TNF-alpha is one of the most potent pro-inflammatory mediators of the immune system.  At proper concentrations it is required for development of memory and synaptogenesis.  At pathological levels it destroys synaptic communication and is part of all neurodegnerative disease states including Alzheimer’s. New evidence points to the effects of TNF-alpha on NMDA receptor function.

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In my clinical practice, I use MgThreonate routinely and it is nearly always helpful in autism. The mechanisms are speculative but it is both effective at NMDA-R restoration as noted above as well as a direct anti-inflammatory.

Tying these seemingly unrelated observations together gets me to where I think autism is taking our understanding.

1). Epigenetic, both prenatal and postnatal effects influence the priming of microglial cells and most assuredly mast cells as well.

2). Mast cells and macrophages contribute to inflammatory changes in the meninges.

3). The immune changes in the meninges opens the tight junctions in the capillaries and allows extra fluid to accumulate in the subarachnoid space.

4). The increased EAF also carries within it the inflammatory chemistry of the mast cells and macrophages.

5). This message also influences the microglial cells and the mast cells resident in the brain.

6). This disrupts minicolumn function and structure.

7). This process prevents the creation of proper harmonic communication in the electrical properties of the brain.

8). The end result is autistic symptoms.

Presumably GcMAF and Magnesium threonate work to restore both microglial cells and macrophages to the ramified supportive non-inflammatory state.  The effect of mast cells in unknown.  But with all of this I believe 2014 is going to bring some amazing breakthroughs for relieving the suffering of autism.

So Happy New Year – 2014

Bravo Probiotic – Actually a System for Making a New Ecosystem NOT Merely a Probiotic

One of the frustrating things in dealing with most chronic illnesses is related to the gut ecosystem. TV ads are now extolling the issues of a bad gut ecosystem so the message about gut flora (the protective bacteria of the intestinal track) is getting much more widely accepted. The challenges I have experienced with many patients, however, makes this far more complex than merely popping a few probiotic capsules.

In previous blogs I have written about fecal transplantation or fecal bacteriotherapy (FBT). Recently the FDA warned doctors to not attempt this without FDA approval making it all but impossible these days.  It has been a successful means of changing out a bad ecosystem in the got for a better one and in cases of life-threatening infectious diarrhea it has been published in the medical literature to be life-saving.

But given the impracticality and regulatory barriers, FBT is not a viable option. So what can we do? My choice is now Bravo and you can find it on the web at www.bravoprobiotic.com. Bravo is a complex multistrain bacterial fermentation process; it is not merely a probiotic and technically it is a fermented dairy product you make in your kitchen by using their system and culture blends.  And if you have been around natural health very long you know most dairy is an issue for children with autism and many other health issues.  However, tests on Bravo at a major university indicate it does not contain casein and other milk proteins after the bacteria digest the milk in the process of fermentation. In my population of sensitive children it has been very well tolerated.

After answering hundreds of emails about Bravo I decided it may be easier to just post this information with detailed pictures of how I make it for myself.

Bravo Maker

You will need a yogurt maker and I chose this one which I ordered from the internet for about $40 US.  I also ordered extra jars because the standard volumes of yogurt suggested in the instructions yields more than the 7 jars will hold.

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Extra jars for the yogurt maker I purchased.  You can get any yogurt maker you like – although Bravo suggests you use one with an automatic shut off.

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I suggest you read the instructions all the way through at least once prior to starting the process and make sure you have all the suggested materials you need.  For me it meant a trip to Target to get a thermometer and a medium metal strainer and a other items like glass jars and special sized cooking pot for boiling the milk. The instructions give you a list of all the material you will need. The instructions talk about a smidgen as a unit of measure.  Technically that is 1/32 of a teaspoon and before you get worried the Bravo starter kit includes a smidgen measuring spoon which you can see on the plate next the to ladle spoon.

The US still uses the Imperial measuring system so for many of you the metric units in the instructions require conversion.  So her are a few tips: 1 liter = approximately 4.23 cups.  The instructions ask you to boil 2.5 litters of milk so that is 10.5 cups (actually a bit more so like 10.6) and there are 16 cups to a gallon so that is more than a 1/2 gallon of milk.  I recommend you use a non-homogenized milk but Bravo instructions don’t mind but they want the full fat milk (whole).  I also suggest you use organic milk. You can use cow or goat or sheep but you cannot use non-mammal milk – meaning almond, rice, soy are all NO-NOs.  You do not need to spend the extra money to buy non-pasteurized since you will boil the milk anyway. They suggest you NOT use the ultra-pasteurized milk now common in stores to increase shelf-life.

As you can see there is a bottle of Colostrum in the picture above.  Kirkman sells a high quality colostrum (milk derived) but again no worries. The dose of colostrum is a little tricky.  The initial suggestion is for 8oz (1 cup) of colostrum (not in the instructions) but that makes the yogurt a little runny.  You need to work on this as time goes on but consistency is not that critical to culture results and health benefits. Temperature conversion are in the instructions.

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Preheating the yogurt maker and cups without their lids for 2 hours is critical.

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In the front is what Bravo calls compound 1 and behind that is compound 2.

IT IS CRITICAL THAT YOU WASH YOUR HANDS, JARS, SPOONS ETC AND KEEP THEM CLEAN AND DRY THROUGHOUT TO PREVENT CONTAMINATION.

I find the taste good without any special flavoring required but then I like real yogurt which is not the sugary stuff we get in the US. You can add honey to it but not until you are ready to serve.  If your child or you are unaccustomed to real fermented food I suggest you go slow and start with small amounts like  a teaspoon and work your way up to large doses.  I suggest adults and teens can have 4 oz a day and medium children 2 oz and little children 1 oz (2 tablespoons are 1 ounce).

Bravo is very responsive to emails so if you have any other questions please contact them about specifics. I hope this is helpful to you all. 

Italian Inspirations for New Therapies for autism – reblogging

Unfortunately my newest blog was accidently deleted in my efforts to learn a new blogging software system (my bad). However it is fresh in my mind and I will take this opportunity to add to it.

Firenze (Florence) was the birthplace of the Renaissance (which in the Italian translation means rebirth) and is an appropriate term for the growing influence of Italy in the research of Autism related disorders. 

First and foremost I must comment on the amazing families who both invited me to Italy and also made the entire trip a huge success (at least from my perspective).  My staff worked long hours to collate  the data and to communicate with the families and especially with Grazia Ciatti who worked amazingly hard to both translate and assist the families in this process.  Professor Marco Ruggiero from the University of Firenze (Florence) graciously contributed to his expertise and new discoveries on GcMAF to the presentations made on the first Saturday of this trip. And without the support of my wife – who both worked with the moms to provide those special touches and supported my efforts and long hours without complain – the trip would have been far less enjoyable.

Ruggiero Lab

Professor Ruggiero in one of his laboratories at the medical school at University of Firenze (Florence).

Ruggiero teaches on GcMAF

Professor Ruggiero was kind enough to present my data to the Italian families (in the Italian language) and together we discussed the ongoing nature of the research and concepts of the autism – immune – brain harmonic linkages.

Ruggiero teaching me about TUS

My time in Italy included hands on training by the professor on the diagnostic process of transcranial ultrasonography – a painless non-invasive technique that can image the temporal lobe with sound waves.

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The space between the two plus signs is the temporal (brain) cortical thickness.

J IiME. 6 (1): 23-28, 2012. Transcranial sonography in the diagnosis, follow-up and treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Ruggiero M, Fiore MG, Magherini, S, Esposito S, Morucci G, Gulisano M and Pacini S.

Brain Stimul. 2012 May 29. Transcranial ultrasound (TUS) effects on mental states: A pilot study. Hameroff S, Trakas M, Duffield C, Annabi E, Bagambhrini Gerace M, Boyle P, Lucas A, Amos Q, Buadu A, Badal JJ.

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TUS is an emerging treatment for the brain that will require more investigation to evaluate its roll in Autism, however it is another promising modality which will be undergoing development in a collaboration with Ruggiero and our group.

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Professors Ruggiero and Pacini (above – also Husband and Wife) collaborated on the creation on a complex strain of multiple bacteria to induce mucosal immune responses similar to GcMAF and to help create a better ecosystem.   A product which is based on their published research is Bravo Probiotic and you can learn more about http://www.bravoprobiotic .com.  The early results from some of my patients throughout the World appear encouraging enough to warrant a formal  clinical study.

Ruggiero and I had some wonderful discussions leading to a plan to implement investigation of a proposed activated form of vitamin D that will have its transport molecule attached.  This will be intriguing and available for testing soon.  More to follow on this.

Florence is an inspirational city with a rich and remarkable history.  The people of Italy were charming and the families I became familiar with made the entire process an unforgettable experience.

Marco Ciatti is the Director of the institute charged with restoration of the amazing artifacts of the country.  Here he kindly is showing my wife (Jennifer) and I the technology used to restore daVinci’s unfinished masterpiece – the Adoration of the Magi. Although uniquely different the science of restoring masterpieces of art is reminiscent of the work we all put in to restoring our children from autism.

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With respect and admiration for the city of Florence and the people of Italy.

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