By Teresa Conrick
For any who don´t know, I have a 24 year-old daughter who regressed into autism before her 3rd birthday. Meg has the type of autism that does not make for an easy life. She lost speech in 1995 and she is nonverbal still, and waves of difficult and painful medical symptoms then were to follow: cognitive decline, increasing GI issues, chronic bacterial infections and viral illnesses, seizures, and then a horrific autoimmune disorder called PANS [Pediatric Autoimmune Neuropsychiatric Syndrome] .
For years now, I have been following the research on the Microbiome as there are solid studies showing how dysfunctional it is in those with an autism diagnosis. Studies like these represent hope for many families with very ill children and young adults:
- Combined oral fecal capsules plus fecal enema as treatment of late onset autism spectrum disorder in children: report of a small case series.
Age and severity may play a part in outcomes with our children as far as treatments. I have now been following the research of Dr. Naviaux, still with the microbiome in mind, but also with a better understanding of its significance. It seems that his research explains much of what I see in Meg, especially with the issues of the gut and brain. You can watch this great video of a lecture by Dr. Naviaux, at a very recent TACA conference. Thanks to them both!
And in that lecture, Dr. Naviaux recommends that viewers read his study called, Metabolic features of the cell danger response http://www.sciencedirect.com/science/article/pii/S1567724913002390. Here are some excerpts:
The cell danger response (CDR) is an evolutionarily conserved cellular metabolic response that is activated when a cell encounters a chemical, physical, or microbial threat that could injure or kill the cell. Common microbial threats are viruses, bacteria, fungi, and parasites. Physical threats include heat, salt, or pH shock, or UV or ionizing radiation. Chemical forms of danger include heavy and trace metals like lead, mercury, cadmium, arsenic, and nickel, certain electrophilic aromatic chemicals like the plasticizer bisphenol A, the chemical flame retardants like the brominated diphenyl ethers (BDEs), and certain halogenated pesticides like chlorpyrifos and DDT.
.... With the discovery that mitochondria represented the front lines in cellular defense and innate immunity, this connection between neurological setbacks and infection began to be understood....An important forcing variable in the control of chronic inflammation and the cell danger response is purinergic signaling...... Likewise, a large number of molecules have been synthesized since the 1850s as dyes, pesticides, drugs, and industrial chemicals. Many are polyaromatic and halogenated. These modern chemicals with conjugated ring systems, multiple double bonds, and delocalized π orbital electron clouds are highly electrophilic and will produce an electron steal within the cell that can also activate the CDR.......vitamin D metabolism is altered significantly by the CDR. .......Acute activation of the CDR stimulates the B6-dependent enzyme histidine decarboxylase to yield histamine....Histamine is also critical for mast cell and eosinophil function in allergy and the anti-parasite limb of innate immunity .....
...The chronic activation of the CDR alters both the physical habitat of the distal bowel and the availability of resources in the form of dietary nutrients. .... and to an increase in gluten sensitivity. These and other factors combine to alter the permeability and species composition in the gut. Among children with ASD, this commonly leads to dysbiosis and alternating bouts of constipation and diarrhea. It also leads to changes in behavior that are a result of communication abnormalities between the enteric nervous system (ENS) that monitors the health and function of the microbiome, and the central nervous system (CNS). Restoring a sick microbiome is not as simple as adding back missing or underrepresented species. Both the physical habitat of the gut and the nutrient resources delivered must be durably changed in order to produce a durable change in the complex microbial ecosystem......Because the CDR is initially adaptive and coordinated by the close interplay of mitochondria and the cell, but becomes maladaptive once the environmental danger is gone, this can be referred to as “anachroadaptive mitocellular dysfunction”......Purinergic signaling appears to play an important role in sustaining the multifaceted metabolic features of the CDR. This observation led to the successful correction of all 16 of 16 multi-system, autism-like features in a classic animal model of ASD using antipurinergic therapy (APT).,,,,,An important caveat to APT is that if the physical, chemical, or biological trigger of the CDR has not been eliminated or neutralized, treatments designed to inhibit a persistent CDR may have mixed effects.
Here is his 2017 paper causing much optimism for parents:
Connections that I would like to point out on this fascinating and hopeful research, since environmental factors have been shown to play a big part:
∗ Are there connections to Hannah Poling, the red-headed, little girl whom the world learned over ten years ago, to have regressed into autism due to Mitochondrial Dysfunction?
∗ “ Any trace or heavy metal that acts as an electrophile or sulfurophile in the cell will trigger a mitochondrial response that is similar to that of a viral infection, because metal electrophiles and replicating pathogens both divert and consume electrons. ”
∗ “ Purinergic signaling appears to play an important role in sustaining the multifaceted metabolic features of the CDR. This observation led to the successful correction of all 16 of 16 multi-system, autism-like features in a classic animal model of ASD using antipurinergic therapy (APT).”
∗ “ We found that disturbances in social behavior, novelty preference and metabolism are not permanent but are treatable with antipurinergic therapy (APT) ... single-dose APT with suramin acutely reverses these abnormalities, even in adults. ”
As I said, much hope for our children here and I am thankful for that. If you would like to support this research, here is information to do just that.
Teresa Conrick is Science Editor for Age of Autism.