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"Century-old drug reverses autism-like symptoms in fragile X mouse model"

Wally

Senior Member
Messages
1,167
Century-old drug reverses autism-like symptoms in fragile X mouse model
Date: January 15, 2015
Source: University of California - San Diego
Summary: Researchers previously reported that a drug used for almost a century to treat trypanosomiasis, or sleeping sickness, reversed environmental autism-like symptoms in mice. Now, a new study suggests that a genetic form of autism-like symptoms in mice are also corrected with the drug, even when treatment was started in young adult mice.
See, http://www.sciencedaily.com/releases/2015/01/150115163535.htm
 

Sushi

Moderation Resource Albuquerque
Messages
19,935
Location
Albuquerque
And further down in the article:
The underlying mechanism, according to Robert K. Naviaux, MD, PhD, the new study's principal investigator and professor of medicine at UC San Diego, is a phenomenon he calls the cellular danger response (CDR). When cells are exposed to danger in the form of a virus, infection, toxin, or even certain genetic mutations, they react defensively, shutting down ordinary activities and erecting barriers against the perceived threat. One consequence is that communication between cells is reduced, which the scientists say may interfere with brain development and function, leading to ASD.

Pretty interesting, thanks Wally!
 

Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
I don't really see how this is an 'autism' model, but anyway... (FMR1 knockout mice, is a model of Fragile-X syndrome, a common cause of mental retardation)

It says on Wikipedia, that Fragile X syndrome co-occurs with autism in about 5% of cases.

The drug they used was Suramin and they demonstrated that it reversed some of the downstream biochemical consequences of absence of FMR1 in mice and along with some reversal of behaviour.

http://en.wikipedia.org/wiki/Suramin (has a worrying side effect profile...)
 

natasa778

Senior Member
Messages
1,774
Significance of the findings discussed here http://www.nofone.org/#!significance-of-naviaux-2015-fragile-x/ctef

What is super exciting here is that they provoked exactly the same neurodevelopmental symptoms and impairments via two completely different upstream mechanisms, and then used the same treatment agent to succesfully reverse symptoms in both cases. Telling us that in order for the symptoms to emerge, something very similar happens to both sets of animals. That a single/similar biological pathway is messed up and causes surface symptoms, regardless of what upstream cause was there to start with, and that this single shared pathology can be potentially amended...


Published paper by Naviaux (there is a thread on it somewhere on this forum) laying out the theory of CDR

Metabolic features of the cell danger response

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 ... 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....
 

voner

Senior Member
Messages
592
thanks Wally and natasa778. Here is a quote from the link provided by natasa778 that I took note of...

When one drug works on two completely different models of a disease, it suggests that it is working in a common way, on a common core pathway of the disease - which for years has been elusive in autism research.

to put in the context of ME/CFS, here is a quote from @Jonathan Edwards in a post on PR I recently made (http://forums.phoenixrising.me/index.php?threads/biomarkers-vs-clinical-diagnosis.34963/#post-546372)....

What we need to know for ME is what pathway needs blocking with treatment (not necessarily with a drug). We need to find a clue to what pathways are critical.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
The CDR came up in a thread some time last year. It kind of makes sense. It has the potential to be useful in ME. What is an issue though is that even relevant mouse models leading to successful mouse treatments fail on humans most of the time. We can view this as interesting, and promising, but need to be cautious. It is however something that we might like to keep in mind.

In particular it might be worth investigating the drug suramin.

It is interesting that I started taking resveratrol largely to act on a path involved in African sleeping sickness. I wonder if this is relevant?
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Very Interesting although I thought the paper we were discussing last year was presented more as a philosophical than a scientific model and claims that the cell danger response was the cause of most human diseases just undermined its credibility.

But, there's some pretty sound and specific science underlying the general notion and I do feel there's a great deal of potential for a similar mechanism to play a central role in ASD and ME/CFS.