Autism Research: Synchrony 2019

<15 min read> 

The public day of Synchrony 2019 conference was in November of last year.

The conference was run by Brain Foundation, which is a unique parent-run organization based in Pleasanton, CA. It funds research to develop treatments and create awareness for medical co-morbidities and disabilities associated with Autism Spectrum Disorder (ASD).

A couple of moms and I went together from the Bay Area in the morning to hear the day’s presentations on research updates. We had to leave around 4 PM, but we heard quite a few talks and I would like to share some of them in this post. 

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Pramila Srinivasan, President of Brain Foundation, gave the introductory address. She mentioned how the foundation is collecting ‘cloud data’ from 400 cities, from 3500 autism patients, This is to gather information on the co-morbidities in ASD. The foundation supported research from a fund of 400K in 2019 and hopes to raise 1.4M in 2020.

1. The first talk was by Sarkis Mazmanian, Professor in Microbiology at Caltech University.

His research is on the Gut-Brain Axis. He spoke on “Microbiome and Autism- basic research to clinical trials”.

Summary: The brain does not work in isolation. Our microbiome has 10^14 bacteria, with >10,000 unique species. It is a like a second genome. There is a vast body of work in animals where microbiome alteration was shown to affect anxiety, learning & memory and appetite & satiety. 

This is because the microbiome regulates the immune system. 70% of our white blood cells are in our intestines, most of our immune cells are in our GI track. It is this connection that regulates our functioning through signaling. 

Most importantly, can we help autism by restoring GI bacteria? Can GI disturbances actually cause autism in some subsets? A transplant of gut bacteria from humans with autism into mice - was found to transfer symptoms of autism to the mice.

Prof. Mazmanian spoke of 4EPS -this was new to me- it is- 4EthylPhenylSulphate,  which is a biomarker for a leaky gut and is high in the blood of humans with ASD. His team is working on a drug that soaks up aberrant molecules from GI track like the 4EPS which interfere with signaling, while the drug itself doesn’t reach the brain. 

2. Micheal Merzenich, CSO, Posit Science Corporation, spoke about Brain Plasticity. His work is on “Brain Plasticity in ASD”.

Summary: The brain has neuro plasticity. We have to look at this neurologically, not psychologically or behaviorally. 

He defined plasticity as ‘about refining your brain connections, to serve your own useful purpose’. The plasticity creates our own special internal version of the world, and creates the ‘self’, a product of a massive schedule of associative self-reference. This ‘self’-creation grows and progressively evolves, specializing and adapting. 

Each one of us has the capacity to remodel our brains, at any age. The processes that express plasticity are reversible. 

Through simple forms of specific brain health training, his team was repeatedly able to show that we can 1. grow brain power and 2. restore neurological integrity in normal and struggling adult human brains. 

Coming to ASD, the tool sets are still incomplete. We need to - a. normalize attention control, b. re-establish and exercise cross-modal integration, c. re-balance and restore neurotransmitter expressions, d. drive and progressively elaborate expressive behaviors. 

However, he noted, there is continual antagonism to re-normalization strategies. 

3. Robert Naviaux, Professor in Residence, Medicine, at UCSD, presented on “Antipurinergic Therapy to decrease core disabilities in ASD”. 

Summary: The healing cycle in the body is broken in all chronic illnesses. It is broken because the Cell Danger Response is invoked by the body after an injury (cuts, infections, trauma, pollutants, pesticides, radiation, etc). This CDR (cell danger response) coordinates the mitochondrial response after every injury. 

Three kinds of mitochondria are needed to heal. Metabolism controls progression through the healing cycle by using metabolites called metabokines as signaling molecules. The healing cycle is a genetically programmed 3-step sequence used to ensure recovery after any type of injury. 

In autism, the healing cycle is broken at the 3rd step called CDR3. Stressed cells leak ATP, which serves as a signaler outside the cell. The lost ATP leaves the cells with insufficient ATP.

Professor Naviaux researched many drugs and found Suramin as a candidate to block this escape route of ATP from the cells in a therapy called ‘Antipurinergic therapy’.

The first human controlled trail of 5 children with a small dose of Suramin was conducted in 2017. The results were very promising. More studies are planned with 50 children. 

4. James Adams, Professor in School for Engineering, Rosa Krajmalnik-Brown, Professor in School of Sustainable Engineering and Daewook Kang, Research Scientist, from ASU, presented on “Microbiota Transfer Therapy for Children with ASD and GI Disorders: Summary of Phase-I and Follow Up”

Summary: Previously in a study by Adams et al, it was found that gut problems in autism were associated with higher symptoms. Treatment by Vancomycin, an antibiotic temporarily improved symptoms. 

Our microbial genome has more than 100 fold more genes than our human genome. Lower microbiome diversity is associated with less healthy gut. A lower microbial diversity was found in guts of children with autism. For example, Prevotella, one kind of bacteria, was dramatically lower in children with autism. This bacteria can serve as a biomarker.

For treatment, children with autism need a broad spectrum probiotic. However, commercial probiotics have only a few bacteria. 

The team at ASU studied 18 children (open label trial) with ASD, ages 7-16, with moderate to severe GI problems using a protocol - MTT (Microbiota Transfer Protocol). All children had GI problems since infancy. An 80% reduction in GI symptoms was seen, stable at 8 weeks post treatment. A 23% decrease in autism symptoms was seen, stable at 8 weeks post treatment. Microbial diversity improved to normal range. A followup study after two years showed GI symptoms improvement at 59% and autism symptoms decreasing by 47%.

Based on this research, MTT for autism has been granted a ‘fast track’ status by the FDA as a promising treatment. Randomized, double blind controlled studies with larger groups are underway. 

5. David Bick, CMO at Hudson Alpha Institute for Biotechnology, presented on “Genomic Testing in Autism Spectrum Disorder”.

Summary: DNA testing is everywhere. However, these tests are not designed to test for genes associated with ASD. In DNA testing, cytogenetic microarray has replaced chromosome analysis. This testing can detect duplications and deletions called CNV (Copy Number Variants). Clinically relevant CNV’s were found in 10% of ASD population (studied 1838). There’s a catalog that lists these CNVs.

Generally, ASD patients have 3 types of genetic testing: Cytogenetic microarray, Fragile X testing and NGS (next-generation sequencing) testing of a panel of genes that have been associated with ASD. This is generally covered by insurance. Two newer tests are being done- Exome and Genome sequencing. However having set panels for ASD can leave out newly discovered ASD associated genes, like the recent ones- variants of CSDE1 (Sept 2019), mutations in TANC2 (October 2019), ELMOD1 gene mutation (October 2019).

Whole Genome Sequencing (WGS) has advantages over Whole Exome Sequencing (WES) because WGS can sequence the exome more accurately and can detect a wider range of CNVs, among other benefits. WGS also finds mitochondrial CNVs. Pharmacogenomic variants can be added to a WGS test.

In connecting testing to treatment, some treatable disorders causing ASD symptomatology were found: ALDH7A1 deficiency causes pyridoxine dependent epilepsy and BCKDK deficiency causes seizures and intellectual disabilities which responded to branch chain amino acid supplementation. WGS and WES can find these disorders. 

He also spoke about possibility of using CRISPR technique for ASD.

6. Ronald Davis, Professor of Biochemistry and Genetics at Stanford University, presented on “The End ME/CFS Project”.

Summary: Like autism, Chronic Fatigue Syndrome (called Myalgic Encephalomyelitis in Europe) is diagnosed by symptoms. 

Professor Davis has a son with CFS so this syndrome is very close to home for him. 

Prof Davis has come up with a novel method to actually measure a biomarker for CFS and use that for cure and for prevention. This holds a strong parallel to autism measurement. 

Devices were fabricated on Silicon wafers and used as nano-needle biosensors. The device layers were SiO2 (100nm)/Au/Si/Au(50nm)/SiO2. Measurements were taken on blood samples with RBC removed and impedence measurements taken at rate of 200/sec.

The impedance was measured in 20 CFS patients and controls- before and after a ‘load’ was added in the form of salt. Because pumping out the Na needs energy, the CFS blood impedance rose way over the control. 

Copaxone, a drug was tested using the same measurements. The impedence from CFS patients samples decreased with the drug. 

He also spoke of microbiome, how those with affected guts are unable to make some necessary products in the guts, like Indole Proprionate. Several CFS patients have mutations in a gene called IDO2 and this, is like a metabolic trap, and can flip the body into a disease state. 

7. Hari Srinivasan, studying at Berkeley for his undergraduate degree presented on the challenges facing individuals with autism who are minimally speaking. 

This presentation and the presence of many other individuals- high schoolers and college students- who are minimally speaking autistic and type to communicate, brought the day-to-day experience of living-with-this-type-of-autism to the foreground.

8. Several other presenters talked about their work, mostly in clinical practice settings. 

My view:

My perspective, as an autism mom and as a person with research background (in non autism area) is on the various angles in the body of work presented on the public day.

1. Gut-Brain connection: A lot of our kids have sensitive guts and related issues. Finding a drug that can soak up ‘aberrant’ molecules coming from the gut can be a life changer for many of us.
2. Diversity of microbiome: I hope this angle, of low diversity of microbiome in individuals with autism, reaches mainstream medicine more, so no infant or toddler, or anyone in autism population is given antibiotics for conditions that can be managed without them. 
3. As a parent, being at ground zero, we see how autism is not ‘static and steady’ but changes everyday within a range. We see amazing differences in how our kids function on a day-to-day level. Brain plasticity is real: “Cross-modal integration” training is what individuals with ASD need, along with the other background factors, which in a home setting, we call ‘we get more done on a good day when autism is low’. This brings to the forefront that there is no one type of autism- there are autisms. If autism is low, which is generally referred to as ‘high functioning autism’, it is indeed understandable to want to emphasize self-identity with a different neurology than typical. But when autism is moderate or high, there is incredible suffering with the co-morbidities for many, along with the core autism. To desire to alleviate the suffering is but natural. 
4. Tying actual loss of ATP, or in other words, energy, in the cell to autism is very exciting. This body of work is actually not just research in autism co-morbidities but hints at the mechanism that may be behind autism.
5. I wonder if the novel device used to measure the ‘energy levels' in blood samples of CFS patients can be used to measure the same in ASD individuals. If this is viable, it can potentially give a non-behavioral measurement for ASD, irrespective of the kind of autism. (Based on the earlier hypothesis that energy has a role in ASD and if loss of ATP in a cell translates to something that can be measured). Can you imagine the possibilities if this works? For one, we can have a biomarker for measuring autism and not based on symptoms alone. 

Please support the Brain Foundation to continue supporting research like the presentations above. It is a parent-run organization- parents like you and me, who are doing this while juggling life and schooling of their kids with autism (some of the parents homeschool their kids). 

Fundraise/Donate

No donated amount is too small, no amount is too big!

Here is a slide from Prof. Mazmanian's talk at the conference. It shows all the areas affected by autism and co-exist with it. 

Here is the link to many of the presentations on the public day of Synchrony 2019 and the dates of the upcoming virtual Synchrony 2020: Synchrony Conference

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My Half-Century.

<reading time 10-20 minutes>


F-i-f-t-y!

One day this summer I turned 50. 

This blogpost is about my half-century. 
For a few months now, I had been feeling a need to explain my ground. So this post, with (pictures!) is, -all-about-me.

***** 

I. 

I grew up in south India in a corner of a city. In a middle-class home, with my siblings, school, community, my mother's songs, books from libraries and books from my father's collection. 

At 22 I came to New York City. I had a fellowship for a Masters in Chemical Engineering. My parents who are from a conservative background let me fly from our family nest on my own. I came to a new place, to a new culture. I lived and learned. Goodness in others helped me in more ways than I can fathom.

Changed schools for a PhD program. A small, memorable wedding in India with S in summer of '92. And I was back to university in Pennsylvania, to grad school research. 

In the same time, we traveled on some weekends, S and I, to see new places and meet new experiences (we lived long distance).

After a year in the mid-west we made a home in the sunny Bay Area in 1997.

Where I worked for some years in the areas of research, development and production of semiconductor processing.

Then, baby. I took time off from my career.

                 






      Baby became toddler. 

II.

Autism.

Autism entered our house without knocking and didn't leave even though I chased after it. And over the years, became family. 

At 40, I was very involved in our son M's coping with autism. He was 5-1/2 years old. I was so involved, I remember saying to myself on my 40th birthday, that my life as I had known was over. I assigned myself to a life of quiet service, of helping and learning. 

A year later I started homeschooling for many reasons1. My instinct was- he sees the world differently, so his learning is different? 

Another year later something unusual happened. I've not spoken to anyone about this because it is difficult to describe. It is coming directly to the blog because I believe I can find the ~right way here. 

***** 

It was late summer or early fall 2010. On one afternoon I found myself at a loss, more than usual.

Here I was, all that I was, how I shaped myself, was around knowledge and experiences. While M, sweet and vibrant, whom I loved more than myself, -then- could speak some words, didn't like to write and stopped reading. He heard differently. His senses processed experiences differently and so he responded differently. 

Medicine at best had mediocre answers. Therapies weren't working for him. This reality ate my insides. It's hunger was high that day.

How did the boy who LOVED to be read to, book after book, disappear? I was holding the void, waiting for him. 

How am I to live? What am I supposed to do? The life that he can't seem to have, how can I have it?

Instinctively, I left aside without prejudice all that I had built up. And subconsciously separated myself from how I had shaped myself.

There was nothing to hold on to. I didn't even know- how to breathe. Not literally, it was as if, -all I was- ..it was as if, -my entire sense of self- had evaporated into the hot day like the thinned air rising from the scorching backyard ground.

And then, when in my afternoon routine of checking the side gate and returning, when___ there was shift in my perspective. The shift was instantaneous. It was as if -a haze cleared up. After standing for a while under the shade of the Persimmon tree in this clarity, I walked away from it to check on M on the other side who was on his disc swing on a Yucca tree branch.

In this new perspective, it didn't matter. It DIDN'T MATTER at all that M was different!

That it didn't matter was insignificant, it was only a small inference from the main of the perspective. I went back to my life with my small family & house, feeling light like a drop on a leaf.

Of course I drift away and get caught up in the flow of heavy or light happenings but always go back as close to and align myself to this perspective as much as I can manage. It is my- one true thing. 

It's like this- imagine you are looking at one of those 3D pictures that were popular a decade or two ago- where you can see one image but if you shift your focus this way and that, you'll see another image. At a point if you can manage, you'll see both. Then you can't unsee one unless you screw up. Even if you lose one, you won't forget and will keep looking for it to make the picture complete again. The new perspective was something like that. 
Until then, I had been with one view. Then unexpectedly, from where my life had taken me and because of M, I was seeing another view, that was underlying this view. This new, second view, or a field as I can best describe it, actually feels the main, the more you feel it. 

It is a totally different feel. 

Then after a year or so later, I recognized that what I've called field, is what has been known since the ages, as --- ~Oneness! 

Oneness is unmistakable.

If someone asks- So what do you have from that?

I'll have this to say- What I have, is, Nothingness.

That is the paradox of Oneness. 

***** 

Over years, I've examined this field from many angles. A part of which is this blog itself. 

It is quite difficult to try and mesh together the 2 distinct views- the one in which we live, and one where there are no differences in we. In one, mountains are mountains and in the boundary between the views, mountains can be pebbles. In one, puddles are puddles, and in the boundary, puddles can be oceans. In one, flowers are flowers. In the same one, there is autism. 

(I hope you noticed that I haven't attempted to describe the actual field- Oneness- itself here. Because it is not for words, intellect or art. Because then the definition will be within wordsese, intellectese and artese.

Also because enough has been said and is being said by many good people about Oneness and such experiences, I have nothing to add. 

Oh, except for my new blog2, where I try to describe how the ancient way of India- of Advaita (not-two)- defines this field. (And how many religions of the world may see the same field differently).

The effort is to explain from my angle which came about as I began to understand. 

While of course, ...whatever is, will always be).

III. 

We continue to ride with the thin and thick of autism. M is growing up through it. He turned 16 in October. We found a way to make schooling work and he is in 10th grade.

In the last few years, something new came about. 

Tentatively, I came up with a model for teaching/learning with a person with autism!

What is the model? Simply, it is to rely on an autism person's strength- generally viewed by mainstream only as a deficit, for learning & living. The strength is what I view as a long-range-intelligence. Relying on it actually makes it possible for a person to manage aspects of the disability with some of their abilities. 

It all started inadvertently, and in retrospect, with a mathematical puzzle when M was 11 or 12. 

It's called the Tower of Hanoi. Solving the puzzle requires some skills - all these are generally considered out-of-scope for M's sub-type of autism. I presented it to him in a certain way and with continued opportunity, he figured it out. 

How? How did it work?

The move from 4 to 5 blocks puzzle was difficult. We tried it on and off over a couple of years in a laid-back way. He would get it sometimes and sometimes not. Then I began noticing a pattern in the instances when the moves were smoother. We stuck to the pattern and viola!

Fast forward to later (and after 6, 7 block Tower of Hanoi puzzles using the same fast(er)-track way, along with observations from other dissimilar puzzles, games, tasks, academics, life and other children and adults over the years, there's this model. There's a method to draw on it. 

The method relies on a person's long-range-intelligence, and offers just-right support while operating in a field of unforced neutrality within our own general field of living&learning, so the person can choose to safely engage on his/her own terms3.

Last year, using this method we tried learning classical music on a keyboard. I picked a little complex song to start with (based on my model). It worked!

It worked! In music, M has joy. Every tune we begin starts off with some effort and as we keep practicing, there comes an inflection point when his ability overrides his disability and he becomes engrossed in the playing, neither looking at the notes nor the keyboard while his fingers are flying. It fills me with wonder and happiness every time. 

***** 

This field-in-a-field method, I think, hope, and that am working with, is about paving a way for M to be all of himself, with his worldview, alongside others as much as he can and wants. 

I believe the new perspective helped set a tone for our homeschooling, and later, helped with going along the path taken. The beauty of the model is that it is easy, and is respectful of student and teacher to the point we may wonder who is who4.

All this is giving me a way to flow more lightly with all life happenings- which is why I was able to write up this blogpost. 

That's my half-century at the crease. I'm happy to be 50. Thank you for reading. 

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Notes. 

1. I wrote about this part of the journey in a previous blogpost. 

2. This new blog is of the two views- I and not-I, and a storyline culminating in one view, hence, the elegant A-dvaita (not-Two).

3. The model is applicable to a wide context. I hope to explain this in detail, elsewhere in future.

4. While easy, applying the model to specific or general skills needs consistent and patient effort. However, we are not on a mission. We'll take it gently, and we're actually quite content with what we have with music.

~~~~~

I couldn't hear a word

Reading time: 2 minutes

One of the two men started it. The younger one. He started telling something and became very animated. Waving his hands, stomping the red earth. By the worn-out van loaded with household stuff and with a hammock in a small side-grove. His entire body became involved in the telling. 

His eyes got bigger. His gestures contracted while he anticipated a response, a reaching out from the other. I stood in the parking lot watching them from about a hundred yards away. We were at a tourist spot famous for watching surfers in Maui. 

Both men were shirtless. Sea-wind seared faces. Lean, muscular bodies. With hungry ruggedness of living solely by the shore. 

The older man, in a red sarong, started listening while walking towards his friend. He slowly got the drift, gave out a guffaw. His body caught the wild story. Wide grins and questions in eyes. Ah, the enjoyment. They kept talking, turning towards each other in circles to hold the tension and vibe. I only followed their body language. I couldn't hear a word. 

We walked up a cliff to a spot to watch the wide ocean. The surfers were magnificent. They paddled in, waited, caught a wave and rode it back with skill. Torso and limbs in perfect coordination. Aligned minds. Majestic. Ah, the thrill. Many came to watch, like us. We dotted the cliffs on the shore. In mid-ocean a couple of surfers casually chatted with each other while waiting for a wave. Bobbing up and down, hanging to their boards. They were far away. I couldn't hear a word. 

Something bothered me. I couldn't figure it out. The something filled me with sadness. Shall we go? I asked my son, 11 then, who had wandered into a grove. Yes, he said, running back. 

It came to me two months later. What had bothered me. 

Their bodies followed their minds. The beach dwellers and the surfers. When erratic or disciplined. In whatever their minds indulged in. A wave or a wild story. Reliably. Dutifully. Not for my son. His body does not easily follow his mind. Even when he wants it to. Autism is a betrayal between mind and body. Like, on the vacation, he wasn't able to sleep at night. No matter how much he tried and wanted to.

How do I know? That his body does not follow his mind? I know because they talk to each other. They keep trying and trying and trying. I can hear every word. 

As his mom, what business do I have in enjoying the coordination of another's mind and body? What about him? Is such coordination the means and end to everything? Am I betraying him by watching? 
Nope, it came to me four years later. There's the body, there's the mind and there's the heart. The heart doesn't use words. It is never not coordinated in feeling. I needed to learn to steer into its band of slowness. 

When I'm there, I can hear the beautiful silence that is behind words. I don't need to hear every word. 

*******

Note: Thanks a local volunteer organization my son, M, went surfing. He was astounded at the experience and became very, very quiet for a few hours. 

Two Poems - 2.

(Continued from previous post)

Over the last five years, I found that it is difficult to navigate a way for meaningful learning and growing, for a child who types.

This niche carving of a small, safe space consumes almost all my energy resources. 

On one hand there is the child with unique expressive ability, different neurology, social construct, sensorimotor mapping, motivations, and, good comprehension. On the other hand are standard educational systems clocked to practical recipes. 

M was tested by his schools- per requirements- through regular academic tests and special tests. He scored well. 

The tests continue to give him a place in this world but they also show the smallness of our testing methods. 

Because to start with, we still don't medically understand autism, what causes it, what it really is! 

I wrote this in 2013 when M first started typing independently. That is, happily typing on an Ipad-keyboard, sitting a small distance way from me. It was a milestone in my world-view. 

This poem somewhat reflects my conflict. 

*****

the secret of dark matter

are leaves green?     is the universe big?

everyone dies, one way or the other?

happiness makes you smile?

songbirds sing?    is he intelligent?

crystal clear, but not apparent to some  

For we judge from what we know    we casually

invalidate the life of another by a  

glance or sound not considering

the arduous path he walked to come here

For a sip of table water   

survival is a daily struggle

When a body is held by autism     a consistent signal-

I am here, I exist, I understand, let me in..

Above the distracting drums of bodily chaos 

is like a revelation on spiral stairs of proofs

but we mostly ask-    can we test?   

it is we who are palaced in boxes of thoughts and doings

we live by the fine satin ribbons tying us up   this is a

designer bow- two twists, 5 loops    so pretty    no ugly    even as our

sight deftly eludes the plain self-sculpturing truth well within

Our boxtrains    chugging chugging on meter gauges    

setting busy systems and metrics for measuring and pouring out

intelligence    so we can pack, box, label and ship it by ground 
to a known place for other bored systems to unpack and assort

our intellect can take only that much, anything more

is taxing to our neural nets    which we tightened nook and neuron,

patient wrench in hand    school and school and school   so we know only

how to grade others to our inflexibilities    Yes he may

Take one sip of life    no he cannot, go to quadrant B, table 3    parents can look

through a window for 3.57 minutes on alternate fridays

can we bottle birdsong?    taste green from a spring leaf?

not seek meaningfulness because we’ll all die anyway?

yesterday you typed, you typed independently.     fully.

met a metric for validation from set systems    so my weak heart

betrays me; it has joy, it is calm    I went to the same life-schools you see

I can’t come out of my box even after opening up box after

box after box    for every x of loosened ribbon knots, y new

ones appear    and loosening one somehow tightens another

anyway I lean back in my box because now I feel more assured

Of standing room for you at the table of the living    I also feel awkward..

I don’t understand. Like someone after figuring out the secret of dark matter

is waiting on a busy, dusty roadside    nervous chalk in hand   

to tell someone     tell anyone 
who stops -   I can write the proof..      independently.      fully.

April 2013