
Low-dose suramin temporarily improves symptoms of autism in small-scale study - jsnathan
https://health.ucsd.edu/news/releases/Pages/2017-05-26-century-old-drug-potential-new-approach-to-autism.aspx
======
blennon
Robert Naviaux is the real deal and his theory on the Cell Danger Response is
fascinating [1]. In addition to ASD, he recently made a significant discovery
in the characterization of Chronic Fatigue Syndrome as a metabolic illness
[2].

[1] [http://naviauxlab.ucsd.edu/wp-
content/uploads/2016/09/cell_d...](http://naviauxlab.ucsd.edu/wp-
content/uploads/2016/09/cell_danger_response.pdf) [2]
[http://naviauxlab.ucsd.edu/wp-
content/uploads/2016/08/PNAS-2...](http://naviauxlab.ucsd.edu/wp-
content/uploads/2016/08/PNAS-2016-Naviaux-1607571113.pdf)

~~~
themgt
Wow, that abstract is quite simply epic:

 _The cell danger response (CDR) is the evolutionarily conserved metabolic
response that protects cells and hosts from harm. It is triggered by
encounters with chemical, physical, or biological threats that exceed the
cellular capacity for homeostasis. The resulting metabolic mismatch between
available resources and functional capacity produces a cascade of changes in
cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid
dynamics, bioenergetics, carbon and sulfur resource allocation, protein
folding and aggregation, vitamin availability, metal homeostasis, indole,
pterin, 1-carbon and polyamine metabolism, and polymer formation. The first
wave of danger signals consists of the release of metabolic intermediates like
ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species
(ROS), and is sustained by purinergic signaling. After the danger has been
eliminated or neutralized, a choreographed sequence of anti-inflammatory and
regenerative pathways is activated to reverse the CDR and to heal. When the
CDR persists abnormally, whole body metabolism and the gut microbiome are
disturbed, the collective performance of multiple organ systems is impaired,
behavior is changed, and chronic disease results. Metabolic memory of past
stress encounters is stored in the form of altered mitochondrial and cellular
macromolecule content, resulting in an increase in functional reserve capacity
through a process known as mitocellular hormesis. The systemic form of the
CDR, and its magnified form, the purinergic life-threat response (PLTR), are
under direct control by ancient pathways in the brain that are ultimately
coordinated by centers in the brainstem. Chemosensory integration of whole
body metabolism occurs in the brainstem and is a prerequisite for normal
brain, motor, vestibular, sensory, social, and speech development. An
understanding of the CDR permits us to reframe old concepts of pathogenesis
for a broad array of chronic, developmental, autoimmune, and degenerative
disorders. These disorders include autism spectrum disorders (ASD), attention
deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other
food and chemical sensitivity syndromes, emphysema, Tourette 's syndrome,
bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD),
chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI),
epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney,
liver, and heart disease, cancer, Alzheimer and Parkinson disease, and
autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and
primary sclerosing cholangitis._

~~~
medymed
This might win the gold medal for loose associations in a non-schizophrenic
context.

~~~
nibs
Schizophrenia is basically symptoms of permeability of the blood brain
barrier. Whole proteins pass through and mess things up. Similar to
automimmune disease. Why else are those diseases on the list the only ones
increasing in pravalence, and all others are decreasing (infectious,
cancerous, viral, etc.). ASD is neuroprotective and tightens those cell
junctions, with behavioral drawbacks. All these things are interrelated, the
issue is they can be caused by 100k different contributing factors and
susceptibilities.

~~~
cheath
increasing in prevalence? or increasing in diagnosis?

~~~
epmaybe
If the diagnosis rate (incidence) increases, and people aren't dying rapidly,
then the prevalence would surely increase as well. Unless you're using
prevalence in the context of total people affected by a disease, regardless of
whether or not they were diagnosed.

~~~
cheath
I meant prevalence in the context of total people affected by a disease,
regardless of whether or not they were diagnosed.

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SubiculumCode
This might help some aspects of ASD. Hopefully. However I do not see how it
will reverse the altered neural migration occurring early in development, for
example, unless it is administered in infancy or earlier while in the womb..

------
Darvict
[https://en.m.wikipedia.org/wiki/Suramin](https://en.m.wikipedia.org/wiki/Suramin)

Things to note:

\- Administered solely by injection.

\- Not FDA approved.

~~~
pavel_lishin
For those of you who read the side effects on the Wikipedia page, the article
addresses 'em:

> _Unlike treatment for African sleeping sickness, which involves multiple,
> higher doses of suramin over a period of time and frequently results in a
> number of adverse side effects ranging from nausea and diarrhea to low blood
> pressure and kidney problems, researchers said the single, low dose of
> suramin used in the ASD trial produced no serious side effects beyond a
> passing skin rash._

~~~
derefr
> It is also common to experience various sensations in the skin, from
> crawling or tingling sensations, tenderness of palms and the soles, and
> numbness of hands, arm, legs or feet.

That's an intriguing symptom, given that many inflammatory/autoimmune
conditions cause peripheral neuropathy. I wonder if what is being described is
the "unblocking" of peripheral nerves, causing a flood of signal-distorting
noise as they re-join the nervous system.

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valuearb
Only 5 kids each for test and control populations.

~~~
Houshalter
Small sample sizes aren't _necessarily_ damning. E.g. if you gave 5 rabies
patients a treatment and they were all instantly cured, that would be
extremely strong evidence it worked. Because rabies is 99.999% fatal and the
chances of 5 randomly chosen people being cured by coincidence is basically 0.

~~~
PhasmaFelis
In this case, for example: "We had four non-verbal children in the study, two
6-year-olds and two 14-year-olds. The six-year-old and the 14-year-old who
received suramin said the first sentences of their lives about one week after
the single suramin infusion. This did not happen in any of the children given
the placebo." That seems promising and worth further study.

~~~
xenadu02
Indeed, the initial results are promising and worth further study with a
larger sample size.

We should be careful though... many results don't replicate in larger
populations.

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donquichotte
From TFA: "Suramin works by inhibiting the signaling function of adenosine
triphosphate (ATP), a nucleotide or small molecule produced by cellular
mitochondria and released from the cell as a danger signal. When CDR is
activated, the effect of extracellular ATP is similar to a warning siren that
never stops. Suramin inhibits the binding of ATP and similar molecules to key
purinergic receptors, according to Naviaux."

Are there any other substances out there that inhibit ATP signaling?

~~~
Ntrails
I vaguely remember ATP from GCSE biology - and in my head it's related to
energy production in cells... I'm curious whether that's merely poor memory or
not

~~~
bitexploder
We could just Google this....but ATP adenosine triphosphate is the preferred
energy source in the cellular energy cycle. A phosphate gets broken off when a
cell uses it leaving ADP which is... Something something, I forget the rest.
It's more expensive for the body to extract energy from ADP.

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lula68
Back at it again with pretending autistic people don't become adults and can't
communicate at all?

~~~
PhasmaFelis
Some of us don't. The article mentions a "14-year-old who had not spoken a
complete sentence in 12 years".

As an autistic adult, it's really frustrating how high-functioning autistics
and caretakers of low-functioning autistics constantly talk past each other
and refuse to acknowledge that the other exists.

~~~
OscarTheGrinch
As one of the aformentioned caretakers I can attest that a certain narrowing
of focus on one's own issues is part of the deal. I also have an autistic
adult friend who is constantly dismayed by the focus on child autisim, so I
can relate to what you are saying.

The focus on children is likley caused by the medical siloing of patients into
pediactric and adult. Also researchers may want to focus on harm reduction, ie
by preventing or amelirating autisitic symptoms in children it is likley to
also prevent the downstream effects to their nervous systems. But certainly if
researchers want to get a better understanding of treatment efficacy, adults
should also be included in trials.

Our current diagnostic grouping of symptoms into an autisic spectrum is
imperfect, I would be very supprised if autisim as we understand it today is
caused by one thing. So if this research becomes a treatment it will likley
only be benificial for a certain percentage.

