Mitochondrial / Purinergic Therapy Corrects Autism in Mouse Model : Connections to ME/CFS?

[Cort]

One of the interesting things about this study is that the purinergic system these researchers targeted has shown up in the Lights ME/CFS exercise and gene expression studies. In fact the same receptor (P2RX7/P2X7) appears to have.

• http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0057380

CFS patients showed higher P2RX7 and lower HSPA2 versus controls and PCF. Correlations with fatigue severity were similar in PCF and CFS for only DBI, the GABA-A receptor modulator (r=-0.50, p<0.005 and r=-0.34, p<0.05). Purinergic P2RY1 was correlated only with PCF fatigue and pain severity (r=+0.43 and +0.59, p=0.025 and p=0.001).

The antipurinergic treatment the researchers did reversed all the metabolic deficits found in the mice. They used something called suramin - which does not appear to be a real possibility. The purinergic connection is intriguing though. Could it play a major role in both ME/CFS and autism?

Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse ModelAbstract

Background

Autism spectrum disorders (ASDs) are caused by both genetic and environmental factors. Mitochondria act to connect genes and environment by regulating gene-encoded metabolic networks according to changes in the chemistry of the cell and its environment. Mitochondrial ATP and other metabolites are mitokines—signaling molecules made in mitochondria—that undergo regulated release from cells to communicate cellular health and danger to neighboring cells via purinergic signaling. The role of purinergic signaling has not yet been explored in autism spectrum disorders.

Objectives and Methods

We used the maternal immune activation (MIA) mouse model of gestational poly(IC) exposure and treatment with the non-selective purinergic antagonist suramin to test the role of purinergic signaling in C57BL/6J mice.
Results

mce-anchor
We found that antipurinergic therapy (APT) corrected 16 multisystem abnormalities that defined the ASD-like phenotype in this model. These included correction of the core social deficits and sensorimotor coordination abnormalities, prevention of cerebellar Purkinje cell loss, correction of the ultrastructural synaptic dysmorphology, and correction of the hypothermia, metabolic, mitochondrial, P2Y2 and P2X7 purinergic receptor expression, and ERK1/2 and CAMKII signal transduction abnormalities.
Conclusions

mce-anchorHyperpurinergia is a fundamental and treatable feature of the multisystem abnormalities in the poly(IC) mouse model of autism spectrum disorders. Antipurinergic therapy provides a new tool for refining current concepts of pathogenesis in autism and related spectrum disorders, and represents a fresh path forward for new drug development.

 

[San Diego]

@Issie - As our resident protozoa expert () I wonder if you have any thoughts on this, since Suramin has been used for decades to treat African Sleeping Sickness caused by the protozoan trypanosoma.

Either way, it is phenomenal that one substance can correct 16 multi system abnormalities! I'd sell everything but my soul for that type of treatment!

 

[Issie]

Haven't heard of it. But there will be some research on my part. thanks for cluing me in to this post.

Issie

 

[Issie]

Side/adverse effects
Signs of potential side effects, especially arthritis; erythematous maculopapular eruptions; nephrotoxicity; neurological complications such as headache, palmar-plantar hyperesthesias, paresthesias, and peripheral neuropathy; pruritus; relative adrenal insufficiency; urticaria; lymphadenopathy; ocular effects such as lacrimation, optic atrophy, palpebral edema, and photophobia; prostration; stomatitis; blood dyscrasias such as agranulocytosis, anemia, or thrombocytopenia; exfoliative dermatitis; hepatitis; idiosyncratic reaction including collapse, nausea, seizures, shock, and/or vomiting; and jaundice
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Side effects seem to be some of the things we are trying to treat. For us with renal and liver impairment wouldn't be so good for us. Also appears to be in the sulfa family of drugs and those of us with CBS mutations don't do well with those drugs.

One thing I noticed, it affects adenosine and D2 receptors. Adenosine has been found to be players in CFS according to research on adenosine by Dr Bateman. I have questioned whether or not dopamine and especially D2 is too high in some. This could explain why research with antipsychotic meds could be beneficial with some. We need to keep in mind this is an animal study that is showing all these markers. This drug isn't available in USA or Canada - so that would make me ask what other alternatives are there with lesser side effects. As for Protozoa, I'm finding that Arteminsin (an antimalarial herb) and Doxycycline are being effective to hold things down to a mild annoyance. Lumberkinase to break down biofilm. And probiotics hours after both types of meds/supplement to keep the gut function optimal. (Doxycycline has been shown to help with immune function. See thread in this forum in regard to this.)

We hopefully don't have the type of Protozoa that they are treating in Africa with this. Being vegan and not eating certain meats may be another good reason for holding closely to this lifestyle of eating.

Issie

 

[Cort]

@Issie - As our resident protozoa expert () I wonder if you have any thoughts on this, since Suramin has been used for decades to treat African Sleeping Sickness caused by the protozoan trypanosoma.

Either way, it is phenomenal that one substance can correct 16 multi system abnormalities! I'd sell everything but my soul for that type of treatment!

It's a rough drug unfortunately..

 

[Cort]

I think Cheney like Arteminsin (an antimalarial herb) It's a pretty powerful substance from what I've read.

 

[Who Me?]

@sdsu Id sell my soul, what's left of it

@Cort there are is another antimalarial that is used for CMV HHV6. The name escapes me now but starts with an A. An IV or IM.