New drug for autism?

Discuss autism diets and biomedical treatments of autism.

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alexsdad
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Re: New drug for autism?

Postby alexsdad » Fri Jan 23, 2015 7:18 pm

Thanks Kulkulkan. Looks like they are mostly using Suramin in the studies listed in the referenced table. At a glance, they all look pretty scary. I will have to go more natural way. So TMP is the first herb listed in the wiki - Ligustrazine or Chuan Xiong. I'm still not clear which P2X subunit I should target. (i.e., P2RX3 vs. P2RX7) Maybe it will have to be trial and error learning but at least these traditional Chinese herbs seem to be safe.

It is interesting your reference range was even lower for the same marker. Now I feel like my son's # is really high.
Last edited by alexsdad on Fri Jan 23, 2015 7:19 pm, edited 1 time in total.

FatherOf2
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Re: New drug for autism?

Postby FatherOf2 » Fri Jan 23, 2015 7:19 pm

We live in San Diego. I had an opportunity to talk to Dr. Naviaux for about 1hr. He is a very brilliant researcher. If I understood him correctly, a single Suramin treatment course may not reverse autism once and for all. Regular IV injections of low-dose Suramin (he mentioned an interval of several months) may be necessary. I guess the study will show. But even if a normal life requires a Suramin injection once every month for the rest of my son's life, I'll gladly take that as long as it doesn't damage adrenal glands, which is one of the major side effects from Suramin. Dr. Naviaux also mentioned that there are dozens of clinical studies of newer drugs with similar action to Suramin started after his publications, mostly targeting rheumatism and other chronic inflammation conditions. Dr. Naviaux also told that some industrial chemicals (e.g. fire retardants in furniture, BPA in plastic bottles) act on immune system the same way as viruses by activating the Cell Danger Response. I am very glad that California finally relaxed the law regarding fire retardants so that new furniture doesn't have to contain them. These chemicals are most dangerous during pregnancy.

alexsdad
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Re: New drug for autism?

Postby alexsdad » Fri Jan 23, 2015 9:34 pm

FatherOf2 - That's great. I agree he is a great researcher. Are you going to participate his trial? His research says most of the improvements were lost after 5 weeks of drug washout. It may be different on human but I think 5 weeks is not bad at all. I really want to find out if my son can benefit from APT. Then I will figure the next step.

FatherOf2
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Re: New drug for autism?

Postby FatherOf2 » Fri Jan 23, 2015 11:46 pm

It all depends if my son is a candidate for this treatment. So far, what he told me about CDR seems to indicate that my son might have it. But I need to ask if there is a test that can be done to show conclusively the presence of CDR in my son. I don't think one theory can explain all cases of autism. By the way, I came to see Dr Naviaux for an opinion on genetic mutations in my son (he is also a geneticist) and then I learned about the Suramin study. This study is not officially announced yet (clinicaltrials has no info on it). So, I am not sure if they are officially recruiting.

alexsdad
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Re: New drug for autism?

Postby alexsdad » Sat Jan 24, 2015 4:41 pm

According to the below timeline, the human trial is scheduled to begin in Q1 2015:

http://www-p.newswise.com/images/upload ... parent.png
Last edited by alexsdad on Tue Feb 03, 2015 12:15 pm, edited 1 time in total.

kulkulkan
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Re: New drug for autism?

Postby kulkulkan » Mon Jan 26, 2015 4:08 pm

Below is a link looking at natural options for inhibition of P2X receptor.

http://www.mdpi.com/1424-8247/6/5/650/pdf

One herb mentioned again is ligustrazine, which has the active ingredient TMP. It has a few studies (mostly for stroke and cardio indications and also has in-vivo study showing reduces microglial activation, activates NF-kB pathway, etc.) and used in Chinese medicine - including IV administration. Oral dosing is possible. There is also mouse study below for Alzheimer's using transdermal delivery but no human studies.

http://www.ncbi.nlm.nih.gov/pubmed/22415639

Paroxetin (Paxil) is an anti-depressant and seemed to inibibit P2X4 function in dose dependent way. Not sure how relevant.
http://www.molecularpain.com/content/5/1/20

autismnhusa
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Re: New drug for autism?

Postby autismnhusa » Mon Jan 26, 2015 6:06 pm

It's just like you close the door when there is a fire in the house. A very stupid approach.

alexsdad
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Re: New drug for autism?

Postby alexsdad » Mon Jan 26, 2015 7:00 pm

Thanks for the links kulkulkan. These are very helpful. I also found the below on the Wrong Planet forum:

http://www.wrongplanet.net/forums/viewt ... p?t=264123


Anyone Tried Kudzu (Ge-Gen, Pueraria) As Antipurinergic...

29 Jul 2014, 5:04 pm

To begin with, let me say that I am thinking here in terms of research, NOT suggesting people run out and do this, because I don't know if it's a good or a bad thing, but I think it would be interesting to know.

Reading papers like www*nature*com/tp/journal/v4/n6/full/tp201433a.html and www*ncbi*nlm*nih*gov/pmc/articles/PMC3596371/ raise the interesting possibility that an antipurinergic drug could "cure" autism, at least in some cases. The drug used in the first paper, Suramin ( en*wikipedia*org/wiki/Suramin]Suramin ), is definitely a broad-spectrum inhibitor of purinergic signalling, but the problem is that (among other things) it is a pretty toxic, nasty drug not readily available for our experimentation.

That said, there really are traditional Chinese medicines with some antipurinergic effects, one of which is a very common herb indeed in some places, namely kudzu (various Pueraria species; known in TCM as Ge gen). Since kudzu (Japanese arrowroot) has been widely used as a food as well as a medicine, I would be hopeful it shouldn't be too dangerous, and I find some indication that kudzu contains components that reduce the expression and therefore the activity of P2X3 ( www*ncbi*nlm*nih*gov/pubmed/19744545 ) and P2X7 ( www*burnsjournal*com/article/S0305-4179(12)00262-8/abstract ); I doubt it is nearly that specific but I don't know. The situation is a little more complicated in that loss of P2X4 ( www*nature*com/npp/journal/v38/n10/full/npp201398a.html ) can cause autism, and loss of P2X2 ( www*pnas*org/content/110/6/2228.full]loss of P2X2 ) is associated with noise-induced hearing damage. The thing is, positive and negative effects are really close together in biology; I think there's something interesting here but it would take more data to understand it.

Which brings me to the question: is there any experience in the community about using this herb, and what effects have been observed? I've been playing with it just recently (still not up to the recommended dose) looking more at metabolic factors like blood sugar and blood pressure, but having had many typical symptoms of autism as a child I am also noting with some interest what I think might be some improvement in executive function, but it is way too soon to reach any conclusion about that even for myself. Anyway, I leave you with these thoughts; make of them what you will.



Interestingly he (or she) had the same question that I have - Which P2X subtype should be the target? There was no response or further follow-up post but I already ordered Kudzu to test P2X3 and P2X7 inhibition as the next step.

autismnhusa wrote:It's just like you close the door when there is a fire in the house. A very stupid approach.


autismnhusa - I'm not sure what you mean. Do you mean inhibiting purinergic receptors would not be a good idea?

FatherOf2
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Re: New drug for autism?

Postby FatherOf2 » Thu Feb 19, 2015 2:03 pm

From the recent article on Suramin (http://ucsdguardian.org/2015/01/22/antiparasitic-drug-found-reverse-autism-mice/)
"What was witnessed in animal models, however, is that after six weeks, the immediate benefits of suramin lost potency, and subjects eventually returned to previous social patterns."

So, to continue the benefits, ASD patients would have to continue administering suramin through IV every 6 weeks. Does it mean that suramin doesn't resolve the main cause why extracellular ATP levels are elevated in ASD patients?

Reading about ATP I found that extracellular ATP is increased in the presence of growing bacteria, fungi, tumors, allergens, inflammatory responses, tissue injury. So, in my simplistic view, suramin for autism is like anti-histamine for allergies. Neither one would resolve the underlying reason for its condition and require a life-long consumption of medication. While anti-histamins are considered to be safe for chronic usage, suramin is not. Perhaps an effort should be made to understand why the extracellular ATP levels are elevated in ASD patients in the first place. Is it due to allergies or hidden bacterial, fungal or viral infections or other toxins?

alexsdad
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Re: New drug for autism?

Postby alexsdad » Thu Feb 19, 2015 7:14 pm

Interesting points, FatherOf2. I'm hoping to see Dr. Naviaux's further research results soon but unfortunately looks like their research fund is coming to an end. Maybe no pharmaceutical company is interested because they don't seem to be able to make money out of this old drug?

JeniB brought up supporting Dr. Naviaux's research via N of One in the below thread before but whoever wants Dr. Naviaux and his research team to be able to continue this project, please read the below and support them:

viewtopic.php?f=4&t=32990

Regarding our own experiment with natural antipurinergic therapy, we've been trialing Kudzu for the past three weeks and the outcome has been pretty impressive. It is still early to say but maybe this will enter the top three interventions. The first thing we noticed was the improvement in his articulation. It happened with the first a few days and soon I realized he started to sleep very well without Melatonin. I haven't seen night awake or silly giggling in the middle of the night since he started Kudzu. Most importantly the mysterious seizure-like episode has disappeared. My wife is not a big fan of biomed but she is onboard with me on this one because of these immediate benefits. No one knows how high we will have to go to replicate the Suramin's antipurinergic effect but probably it won't happen with Kudzu alone. As I study this matter more, it makes more sense that Dr. Naviaux uses Suramin for his research. Suramin is a broad spectrum antipurinergic drug and it suppresses both P2X and P2Y signaling. Actually the effects of the CDR on P2X signaling to be only about 20% as important as the effects on P2Y signaling according to Dr. Naviaux. My next goal to find the natural substance that can mimic Suramin's P2Y signaling. (ideally the same P2Y subtypes) For the past several days I've been trying to find another herb (or light commercial drug that my DAN would be willing to prescribe) that inhibits P2Y signaling but no success yet. There are many people on this forum with better research skills so hopefully someone can help.

FatherOf2
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Re: New drug for autism?

Postby FatherOf2 » Thu Feb 19, 2015 7:24 pm

alexsdad, which brand of Kudzu are you using?

alexsdad
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Re: New drug for autism?

Postby alexsdad » Thu Feb 19, 2015 7:42 pm

I used this:

http://www.amazon.com/Planetary-Herbals ... ords=kudzu

But considering switching to this:

http://www.amazon.com/Vitacost-Kudzu-Ro ... ords=kudzu

Mainly because Kudzu from Planetary Formulas contains calcium and I don't want to overdose calcium.

JeniB
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Re: New drug for autism?

Postby JeniB » Fri Feb 20, 2015 7:55 am

Interesting fact about Kudzu, it is also used to treat alcoholism. It supposedly suppresses the desire to drink. I know, because my dad was an alcoholic and at the time we were desperate to just help him stop because he wasn't going to go anywhere to get help...this was pre-autism for us (the beginning of my research days!). Lots of good information on kudzu.
Jen
(mom of 3)

iherb referral code: HOF516
save $5 on first purchase

kulkulkan
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Re: New drug for autism?

Postby kulkulkan » Fri Feb 20, 2015 6:14 pm

@alexsdad - thanks for the update on Kudzu.

Suramin appears to act as known antagonist on P2X2, P2X5, P2Y2, P2Y4 and P2Y11 receptors. P2X4 receptors were relatively insensitive to suramin or only weakly sensitive to suramin according to couple of studies, which is probably a good thing.

Not sure how relevant but with respect to P2Y2 receptors (which are expressed in immune cells) from review below:
http://www.mdpi.com/1420-3049/17/11/13009/pdf
In relation to P2Y receptors, Mendes and colleagues, in 2003, observed P2Y1 or P2Y2 receptors’ participation in the mechanism of the vascular relaxation produced by polyphenolic substances from red wine [34]. Kaulich and colleagues evaluated a series of 40 flavonoids as antagonists at P2Y2 receptors expressed in NG108-15 cells. By measuring the inhibition of UTP-stimulated intracellular calcium release, they identified diverse flavonoids as potent antagonists at P2Y2 receptors, with IC50 values in the low micromolar range and potency similar or higher than the standard P2Y2 antagonists Reactive Blue 2 and Suramin [26].

Of the 40 flavonoids studied in the Kaulich study, the three compounds that had most potent P2Y2 antagonism were kaempferol, heptamethoxyflavon, and tangeretin. These flavonoid compounds do have separate studies as well and found in various fruits and vegetables. Haven't looked at what supplements have these. Not much info on natural P2Y4 or P2Y11 antagonists.

alexsdad
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Re: New drug for autism?

Postby alexsdad » Fri Feb 20, 2015 7:01 pm

Thanks kulkulkan! You are really good at finding all these! I wonder if we are using the same Google search engine :)

I saw the similar info in the below research regarding P2X and P2Y receptors (table 1 on page 2):

http://www.tocris.com/pdfs/pdf_download ... Review.pdf

Kaulich staudy is very interesting. I need to research more on this. P2Y2 may play an important role in autism since it appears to be mainly distributed in the immune cells. I'm guessing these are the areas that Dr. Naviaux will need to research more in order to develop the drug that targets specific purinergic receptors.

kulkulkan
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Re: New drug for autism?

Postby kulkulkan » Fri Feb 20, 2015 7:52 pm

My source was the same (tocris) for suramin's antagonist action :)

Dr Naviaux first needs to prove APT hypothesis using suramin in humans. And even if Suramin works in human trials, that doesn't necessarily prove the APT hypothesis for ASD. Here is a different interpretation (speculation?) on suramin from Prof. Theorides. Still a long way to go but it it works, it is a big step in right direction.

http://www.autismfreebrain.org/sites/de ... 8-2013.pdf

alexsdad
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Re: New drug for autism?

Postby alexsdad » Fri Feb 20, 2015 10:45 pm

Yup. That's why I want Dr. Naviaux to be able to continue his research and have an opportunity to prove his theory is right. (or wrong) FatherOf2 made a great point above regarding the use of anti-histamine to address elevated extracellular ATP. That's Dr. TT's approach. Dr. TT and Dr. N are in the same field and their theories are actually very similar. I just realized that Dr. TT is the one behind Neuroprotek. No wonder Dr. TT is bashing Dr. N.

luis
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Re: New drug for autism?

Postby luis » Sat Feb 21, 2015 8:17 am

Alexsdad,

Which dosage of Ku Dzu are you using, please ?
Luis

alexsdad
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Re: New drug for autism?

Postby alexsdad » Sat Feb 21, 2015 10:24 am

luis wrote:Alexsdad,

Which dosage of Ku Dzu are you using, please ?
Luis


My boy is 7 year old and 32kg. We went up to 8 tablets per day (twice the recommended dose per label) with the below product. I'm not sure if there was any additional benefit after the first 2 to 4 tables per day:

http://www.amazon.com/Planetary-Herbals%20...%20ords=kudzu

Unfortunately my son had the seizure-like episode this morning. Last episode was three weeks ago and before he had it almost every other day. Interestingly it looked more like a GI episode than seizure this morning. We are going to lower the dose but will have to see if this will still happen infrequently or the benefit of Kudzu (or something else) has ended. This is puzzling me now but I will do some investigation and share my findings here.

Just be careful if are going to trial Kadzu anyway. Even though this herb has been used to treat alcoholism for ages we don't really know the toxicity profile of the components. Botanical extract is a blend of many active ingredients and sometimes you encounter toxicity of another ingredient before you can achieve an optimum effect from another ingredient.

luis
Posts: 257
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Re: New drug for autism?

Postby luis » Sat Feb 21, 2015 1:37 pm

alexsdad wrote:
luis wrote:Alexsdad,

Which dosage of Ku Dzu are you using, please ?
Luis


My boy is 7 year old and 32kg. We went up to 8 tablets per day (twice the recommended dose per label) with the below product. I'm not sure if there was any additional benefit after the first 2 to 4 tables per day:

http://www.amazon.com/Planetary-Herbals%20...%20ords=kudzu

Unfortunately my son had the seizure-like episode this morning. Last episode was three weeks ago and before he had it almost every other day. Interestingly it looked more like a GI episode than seizure this morning. We are going to lower the dose but will have to see if this will still happen infrequently or the benefit of Kudzu (or something else) has ended. This is puzzling me now but I will do some investigation and share my findings here.

Just be careful if are going to trial Kadzu anyway. Even though this herb has been used to treat alcoholism for ages we don't really know the toxicity profile of the components. Botanical extract is a blend of many active ingredients and sometimes you encounter toxicity of another ingredient before you can achieve an optimum effect from another ingredient.


I'm sorry for the seizure-like episode. What do you mean by a "GI episode" ?

I've started giving Kudzu to my son, 3 capsules (500 mg each) per day, since yesterday.


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