Friday, June 3, 2011

One of these years I have GOT to get to the Autism 1 Conference...

One of the ladies on the BeyondGFCF yahoo group kindly took copious notes at Dr Bradstreets lectures... here are the segments that I found really interesting in relation to Dominic.    I'm documenting them here so that I remember that I want to dig further into a lot of this stuff w/Dr K.


Dr. Bradstreet's talk, A1 2011:

(Dr. Bradstreet = DB)

1. TNF-alpha

DB explained how the article "Beneficial neurological effects observed in a patient with psoriasis treated with etanercept" was a big revelation for him:

Am J Clin Dermatol. 2010;11 Suppl 1:44-5.
Beneficial neurological effects observed in a patient with psoriasis treated with etanercept.
Bassi E, De Filippi C.

A 53-year-old woman with a history of psoriasis presented with severe cutaneous lesions associated with psoriasis. The woman was mentally handicapped; she was able to converse monosyllabically with her mother only and was very limited in social interactions. After preliminary investigations, a biological treatment was proposed. Etanercept was started in October 2006. The patient responded rapidly and, after 3 months, achieved a 75% improvement in the psoriasis area and severity index (PASI 75) score. Most notable, however, was that she began interacting with other people, even if they were not familiar to her. Subsequent cutaneous relapses were treated successfully with etanercept. Very few articles regarding etanercept and neurological or psychiatric problems are present in the literature. According to recent studies, etanercept could improve verbal fluency and cognitive and behavioural functions in Alzheimer's disease, so that we can suggest a potential role and use in neurological disorders.

DB explained that this article show how powerful an effect reduing TNF-alpha can have on autistic symptoms. He cautioned that Ethanercept is not a safe medication to treat autism due to its complications (lymphomas and worsening of IBD), but we need to seek other ways to reduce TNF-alpha.

2. GcMAF and nagalase

DB stated that vitamin D regulates the gut microbiome..  GcMAF is the activated receptor of vitamin D, and allows the macrophages to target cancer cells.

The enzyme nagalase is produced by infected cells and blinds the macrophages, preventing them from killing cancer cells, in other words, nagalase acts as a defense screen for infected cells.

Now if GcMAF is injected in the patient together with vitamin D, it drops this defense screen and allows the macrophages to do their job, leading to:
- complete clearing of HIV
- remission from metasatic tumors

GcMAF research is done in Europe but not in the US.

3. Inflamation
DB stated that experiment have shown that elevated pro-inflamatory cytokines directly cause avoidance of eye-contact.

The MIND Institute found auto-immunity in children with autism and in the mothers, but the auto-immunity found in mothers is different than the one found in children, interestingly.

DB reiterated that the #1 effective treatment for autism (according to parents, I guess), is chelation.

The more immunodeficient the kids are, the worse the autism.

DB then explained that ingestion of gluten, soy and dairy generate a huge increase in TNF-alpha. That in itself can explain why GFCFSF diet can be effective in autism, because it decrease the TNF-alpha production. This DOES not involve traditional allergic responses though, the TNF-alpha production resulting from these proteins follows another mechanism, and involves many more proteins than just those from gluten, soy, and casein. For instance, BD stated that at one point anything fed to his son would generate a reaction.

DB then cautioned against Neuroprotek: quercetin has negative side effects, on one hand it blocs the production of serotonine, andon the other hand, substances in quercetin can convert to (quinolinic acid), a powerful neurotoxin.

4. Persico's work
DB then talked about Persico's work, especially his finding of elevated P-cresol in the urine of children with autism. P-cresol is the most neurotoxic substance known. Only one lab in the world can test for it, Laboratoire Philippe Auguste in France. It is believed that clostridia bacteria in the gut produces P-cresol from phenols found in the diet.

DB also spoke of Persico's findings that viral persistence of polioma viruses in the brain is more common in autistic patients than controls (even though everybody is exposed to these viruses).

Persico did not find more HHV6 in autistic brains than in controls.

DB then stated that persico was wise enough not to look for the measles virus, because he knew that if he would look for it and find it, it would be the end of his carreer. DB reiterated that several years ago, when he was still doing spinal taps on patients, he did find measles in the CSF of autistic patients.

5. Down syndrome
DB mentioned that incredibly, the inflamatory profile seen in Down syndrome matches the one seen in autism, though we don't know why.

6. Finegold's work
DB explained that the gut mucosa needs adequate levels of cysteine and vitamin D to have adequate defenses against bacterial overgrowths of clostridia and desulfovibrio.

-> If cysteine and/or vitamin D are deficient, the intestinal mucosa won't be able to control these overgrowths.

(My note: folate is needed to produce cysteine, and folate receptors are present on gut mucosa, so maybe folate antibodies might be an issue there too, in addition to vitamin D deficiency, B12 deficiency, and/or methylation problems.)

Finegold also found that desulfovibrio is more prevalent in autistic children. The telltale sign that someone has overgrowth of desulfovibrio is a rotten egg smell after ingesting garlic, DMSA, etc... because the bacteria feeds on the cysteine present in these and produces hydrogen sulfide.

7. DB musing
DB theorizes that autism involves:
- a persistent pathogen inducing loss of self-tolerance (autoimmunity).
- loss of stem cells and counter-regulatory TREGs
- deficiency in transforming growth factor

8. Cyclic Cidofovir
Efficient antivirals are lacking. Cyclic Cidofovir is a very toxic antiviral, which can become much less toxic and much more efficient if encapsulated in a liposome.

Cidofovir-loaded liposomes are effective against lymphoma.

Unfortunately, the liposomal formulation is not available yet, but we should keep this in our radar as potentially effective treatment coming in the future.

9. Cholinergic abnomalities
There is evidence of reduced cardiac parasympatic activity in children with autism, with cholinergic abnomalities.

The cholinergic anti-inflamatory pathway has not been explored much but could be promising in autism.

Drugs affecting the cholinergic function are:
- galantamine (modestly effective)
- nicotine (very effective, as patch)
Nicotine and galanatime given together have been found very effective to reduce microglial activation in HIV encephalitis.

Namenda was found effective to increase cognition and language.

Nicotine at low dose inhibits dopamine. Nicotine at high dose has a stimulant effect.

Nicotine was found as effective as sulfasalazine to treat UC.

CDP-choline can be effective (available OTC as cognizine).

In DB's experience, azithromicin is not effective anymore against strep. The only effective antibiotic now is Augmentin, but it is very damaging for the flora.

11. CNS anti-inflamatory drugs
DB does not recommend NSAIDs anymore because all of them except Naproxen have been found to cause cardiovascular disease. And unfortunately, Naproxen isn't that effective.

BD stated that curcumin isn't absorbed, and doubts that Enhansa is any better absorbed than plain curcumin. In order for curcumin to be absorbed, it must be in a liposomal form.

-> Check Nutrivene (makes liposomal curcumin, CoQ10, etc...)

DB loves and hates steroids. To be used very cautiously. Better avoided.  IVIG is pretty safe, sometimes awesome, more often completely ineffective.

Spironolactone is very effective at reducing TNF-alpha and has minor side effects only.

DB does NOT like minocylcine, too many problems with it, including hearing loss.

DB then spoke about a study (missed that) that found pioglitazone dramatically effective at reducing TNF-alpha. This part however WAS NOT published in the paper because of a minor flaw, but the fact remains that the researchers found pioglutazone very effective to lower TNF-alpha.

Administration of IV glutathione does not cross the BBB. One way to increase glutathione in the CSF is to administer IV NAC.

CoQ10 is very poorly absorbed. To be absorbed it must be in a liposomal form (Vitaline has the patent for that).

12. Biomarkers
Oxidative biomarkers available at Laboratoire Philippe Auguste:
- isoprostane
- 8 OHG

Inflamatory biomarkers:
- Biopterin
- Neopterin
Neopterin production is very high in cancer and HIV.Neopterin is upregulated by nagalase.
Cysteine and glutathione.
Ammonia and lactic acid (very difficult to get accurate results from labs)

Markers of inflamation in the GI tract:
- Lactoferrin
- Calprotectin
- Elastase
- Reducing substances

Genova is the only lab that can measure calprotectin, and it is the best marker for IBD.

13. Nagalase
Eelvated nagalase is found in the blood of autistic children and their mothers. Cancer, HIV, chronic infections will increase nagalase. DB mentioned that it is not clear yet if XMRV increases nagalase as well.

-> This suggests that there is a pathogen involved in autism but we don't know what it is.

14. Folate, RBC
DB mentioned the folate antibodies.

He also mentioned that in his practice he find many children with elevated MCH and MCV. He is suggesting paying more attention to this and see whether this might have pathological implactions, e.g. hypoperfusion of capillaries (due to large RBCs).

He also mentioned that children on Leucovorin for several months start showing a reduction in MCH/MCV.

15. Physician discussion
a) As many as 25 different brain auto-antibodies have been found in autism. They are not necessarily pathological, but suggestive of B cell dysfunction.

b) DB does not believe in chelation suppositories.

c) DB mentioned that since the Geiers lost their license, DMPS got a very bad press and it might be risky for doctors to use DMPS now, whereas for DMSA there are several supporting studies available.

d) Autoimmunity is not necessarily equivalent to autoimmune disease, but reflects immune dysregulation and persistent pathogen.

e) DB said in his opinion chelation helps in autism because it is a powerful radical scavenger, and thus reduces oxidative stress. But he does not believe removal of heavy metals is the main mechanism that improves autism, because he does notget many metals out of kids anymore, and chelators won't chelate any metals as long as there is oxidative stress. Oxidative stress must be down first before chelators can chelate. however, chelation remains #1 effective treatment, but likely it is through oxidative stress reduction that it is working. Dr. Frye agreed and said DB's explanation was excellent.

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