New drug for autism?

Discuss autism diets and biomedical treatments of autism.

Moderator: ModeratorBill

borsooq
Posts: 150
Joined: Fri Feb 22, 2013 11:28 am

New drug for autism?

Postby borsooq » Thu Mar 14, 2013 1:26 pm


kulkulkan
Posts: 2075
Joined: Tue Mar 13, 2012 1:37 pm

Re: New drug for autism?

Postby kulkulkan » Thu Mar 14, 2013 2:02 pm

Thanks for posting. Very interesting indeed. I will post the original article/study in the Research article section.


FatherOf2
Posts: 1587
Joined: Mon Mar 11, 2013 1:37 am

Re: New drug for autism?

Postby FatherOf2 » Thu Mar 14, 2013 2:21 pm

Exciting!!!
I wonder how safe this drug is. I found this info about suramin, but may be the doses used were too high:
http://news.google.com/newspapers?nid=950&dat=19860625&id=wbhaAAAAIBAJ&sjid=8VkDAAAAIBAJ&pg=5672,2525367

Suramin treats African sleeping sickness and river blindness by inhibiting growth factors within the parasites that cause the disease. By reducing the ability of worms and nematodes to produce insulin, platelets, and dermal cells, the drug interferes with the parasites' ability to replace old cells and produce energy. As their energy levels drop, the parasites face eventual immobility and death.

Experimental trials conducted since the late 1980s have shown a link between suramin treatment and the growth inhibition of a range of neoplastic tumors. Its potential value as an anticancer agent is based on its ability to slow the growth of inoperable tumors in metastatic cancers, increasing the possible effectiveness of other cancer treatments. Trials have not moved past the clinical stage, mostly due to uncertainty surrounding the exact mechanism by which suramin inhibits tumor growth and the discovery that the drug actually accelerates the growth of certain kinds of cancer.

Suramin treatment can lead to a number of potential side effects, most commonly nausea, vomiting, and an itchy rash. More seriously, it can also cause kidney damage in some individuals, and is generally not prescribed to those with existing renal problems. The drug is capable of causing temporary or permanent impairment of the adrenal cortex in rare cases. Overdose can lead to kidney damage and possible renal failure. Serious side effects are relatively rare, and the drug is considered safe in most cases.

dabaxter
Posts: 4052
Joined: Wed Nov 14, 2007 12:50 pm

Re: New drug for autism?

Postby dabaxter » Thu Mar 14, 2013 4:35 pm

Very interesting!
$5 off iherb.com. Use:REW815/$5 off pureformulas.com Use:RJNXCX

AnxiousDad
Posts: 552
Joined: Thu Feb 24, 2011 1:05 pm

Re: New drug for autism?

Postby AnxiousDad » Thu Mar 14, 2013 5:56 pm

So what is this? Are these doctors acknowledging that there is an organism involved here and that is why they are treating it with Sumarin?? What is going on here?

kulkulkan
Posts: 2075
Joined: Tue Mar 13, 2012 1:37 pm

Re: New drug for autism?

Postby kulkulkan » Thu Mar 14, 2013 6:29 pm

AnxiousDad wrote:So what is this? Are these doctors acknowledging that there is an organism involved here and that is why they are treating it with Sumarin?? What is going on here?


Not at all. I posted the study in research forum. The study was based on an autoimmune mouse model (mother was infected with some virus during critical phase of pregnancy). This drug was used to test hypothesis that autism maybe caused due to improper response due to "danger" signaling between cells. This drug may somehow inhibit that (and appeared to work in the mouse model). For all we know both the hypothesis and mouse model could be completely wrong. Next step is to test hypothesis on small scale clinical trials in humans.

TamiW
Posts: 3855
Joined: Fri Feb 25, 2005 12:46 pm

Re: New drug for autism?

Postby TamiW » Thu Mar 14, 2013 8:29 pm

AnxiousDad wrote:So what is this? Are these doctors acknowledging that there is an organism involved here and that is why they are treating it with Sumarin?? What is going on here?

That's where my brain went too! Especially with this quote: 'When cells are exposed to classical forms of dangers such as a virus, infection or toxic environmental substance, a defence mechanism is activated,' said the professor.
'This results in changes to metabolism and gene expression (activity) and reduces the communication between neighbouring cells. Simply put, when cells stop talking to each other, children stop talking.'

Read more: http://www.dailymail.co.uk/health/artic ... z2NZ11zvmk
Tami

FatherOf2
Posts: 1587
Joined: Mon Mar 11, 2013 1:37 am

Re: New drug for autism?

Postby FatherOf2 » Thu Mar 14, 2013 9:07 pm

This is how I understand their theory, which makes a lot of sense to me. Something (e.g. virus, or may be a vaccine, or some toxin like mercury or lead, or an allergen like casein or gluten) triggers cells to go into autoimmune defensive mode, in which cells communicate a "danger" signal to each other (purinergic signaling) and which prevents the proper development of the brain. Apparently, this is the same defensive mode that the cells use in the state of persistent (chronic) pain. And in this state the excitability of sensory neurons is highetened, which perhaps explains why autistic children are so sensitive to noise and other external stimuli. The brain cells stay in this defensive mode until the trigger is removed (for example, mercury is removed from body, or a virus is killed, or gluten/casein removed from the diet, etc). That may be why chelation, antiviral drugs and GFCF diet work. Or, may be, the cells can just get stuck in this mode even if the trigger has been removed long ago (like a vaccine).

So, this drug, suramin, blocks the receptors of the "danger" signal (purenergic receptors), allowing the cells to communicate with each other normally. The interesting thing is that these are the same receptors that control inflamation and blood clotting. I am not a scientist, but this is what I understood from reading about these receptors. Suramin also inhibits growth factors of cancer cells, but the scientists didn't talk about this much, perhaps assuming that this property is not important for autism. So, suramin has anti-viral, anti-cancer, anti-pain, anti-inflammatory and anti-coagulation properties. But, it is quite toxic (I wonder how many mice died in the experiment). I sent an email to UCSD asking about their plans to start a study on humans. Here is the reply I got from a PR person:

"I don't believe the researcher seeks trial participants at this time. It is, as you read, still at very early steps, in a mouse model of autism."

So, while we wait for the scientists to start a human study, we can find natural substances that have similar anti-cancer, anti-viral, anti-pain, anti-inflammatory and anti-coagulation properties. Some come to mind:

- Curcumin (one of the strongest natural anti-cancer remedies)
- Garlic (this one is good for everything)
- Ginger (did you know that it is more potent than aspirin?)
Last edited by FatherOf2 on Fri Mar 15, 2013 12:59 am, edited 1 time in total.

marciogama
Posts: 53
Joined: Tue Aug 14, 2012 4:54 pm

Re: New drug for autism?

Postby marciogama » Thu Mar 14, 2013 10:52 pm

AnxiousDad wrote:So what is this? Are these doctors acknowledging that there is an organism involved here and that is why they are treating it with Sumarin?? What is going on here?


Yes, they knew all the time. The good thing about all this is that we are on the right track (chelation, antivirals...).

kulkulkan
Posts: 2075
Joined: Tue Mar 13, 2012 1:37 pm

Re: New drug for autism?

Postby kulkulkan » Fri Mar 15, 2013 12:26 am

Here is link to the complete study again. http://www.plosone.org/article/info%3Ad ... ne.0057380

The xenobiotic cause could presumably be anything - brain injury, epigenetics, viral, metals, etc. - in the study a maternal immune activation (induced by viral agent) autism mouse model was used. The hypothesis, if true, would certainly validate xenobiotic as potential cause of autism, which in my opinion is the majority of ASD cases. Problem would still be that we wouldn't know what is the prevalent underlying cause.

The drug suramin used in this study is a "non-specific" purinergic antagonist - as fatherof2 pointed out, there are very specific purinergic signalling pathways being researched with respect to inflammatory, pain, and neuro-degenerative disorders (e.g. alzheimers, brain injury, etc.) and if proven, presumably over time, more specific anti-purinergic therapy (APT) class of drugs will be developed. I think we are still at least a decade away from that, so in the interim, can only try biomed approaches that attempt to address a variety of potential underlying causes as well as symptoms.

marciogama
Posts: 53
Joined: Tue Aug 14, 2012 4:54 pm

Re: New drug for autism?

Postby marciogama » Sat Mar 16, 2013 12:18 pm

Fifteen different isoforms of purinergic receptors are known that are stimulated by extracellular nucleotides [18]. These are divided into ionotropic P2X receptors and metabotropic P2Y receptors.


Purinergic (P2X) Receptors Antagonists

http://www.tocris.com/pharmacologicalBr ... USO1hdwdpA

It seems there are few alternatives to the drug suramin. And no natural herb alternative, since these purinergic receptors are not well understood yet.

alexsdad
Posts: 134
Joined: Fri Dec 30, 2011 1:31 pm

Re: New drug for autism?

Postby alexsdad » Sat Mar 16, 2013 3:53 pm

Anyone interested in trial? It looks like this drug has been out there forever and the side effects are well understood. Unfortunately Suramin is not available in US so I doubt if there is anything my DAN can do. I wonder if those alternatives marciogama mentioned may be used instead in US.

FatherOf2
Posts: 1587
Joined: Mon Mar 11, 2013 1:37 am

Re: New drug for autism?

Postby FatherOf2 » Sun Mar 17, 2013 3:47 pm

alexsdad wrote:Anyone interested in trial? It looks like this drug has been out there forever and the side effects are well understood. Unfortunately Suramin is not available in US so I doubt if there is anything my DAN can do. I wonder if those alternatives marciogama mentioned may be used instead in US.


I don't think they will ever start suramin studies on autistic children. Here is what the conclusion of the full article says:

"Long-term therapy with suramin in children with autism is not an FDA-approved usage, and is not recommended because of potentially toxic side effects that can occur with prolonged treatment [61]. However, antipurinergic therapy in general offers a fresh new direction for research into the pathogenesis, and new drug development for the treatment of human autism and related spectrum disorders."

A quick check in Wikipedia reveals that "There is a greater than 50% chance of adrenal cortical damage, but only a smaller proportion will require lifelong corticosteroid replacement." That is way too much risk for me. Suramin is used to treat African sleeping sickness which is fatal and so giving suramin seems like a better alternative than dying:

"Without treatment, the disease is invariably fatal, with progressive mental deterioration leading to coma, systemic organ failure, and death. An untreated infection with T.b. rhodesiense will cause death within months[9] whereas an untreated infection with T.b. gambiense will cause death after several years.[10] Damage caused in the neurological phase is irreversible.[6]"

dabaxter
Posts: 4052
Joined: Wed Nov 14, 2007 12:50 pm

Re: New drug for autism?

Postby dabaxter » Mon Mar 18, 2013 8:34 am

I read there were a lot of deaths in the HIV trial. I don't think I'd be first in line for this clinical trial.
$5 off iherb.com. Use:REW815/$5 off pureformulas.com Use:RJNXCX

kulkulkan
Posts: 2075
Joined: Tue Mar 13, 2012 1:37 pm

Re: New drug for autism?

Postby kulkulkan » Mon Mar 18, 2013 11:11 am

I agree that small clinical trial is unlikely given the serious side effects. There are other P2X antagonist drugs in the pipeline (for arthritis) - replicating results in humans is much harder than mouse model.

Here is a good review on P2X receptors and research.

http://www.ucl.ac.uk/ani/GB's%20PDF%20f ... CV1317.pdf

It mentions DHEA as a potential P2X receptor modulator and the Chinese herb medicine extract TMT as potential antagonist. None of these have really been studied much in context of P2X role. Magnesium (Mg2+) is also mentioned but again not studied in this context.

marciogama
Posts: 53
Joined: Tue Aug 14, 2012 4:54 pm

Re: New drug for autism?

Postby marciogama » Mon Mar 18, 2013 3:45 pm

kulkulkan wrote:
Here is a good review on P2X receptors and research.

http://www.ucl.ac.uk/ani/GB's%20PDF%20f ... CV1317.pdf

It mentions DHEA as a potential P2X receptor modulator and the Chinese herb medicine extract TMT as potential antagonist. None of these have really been studied much in context of P2X role. Magnesium (Mg2+) is also mentioned but again not studied in this context.


From this thread:
viewtopic.php?p=160211
"Magnesium and DHEA go together. When we raise intercellular magnesium, we raise DHEA. This is the natural way to raise the body's DHEA levels."

FatherOf2
Posts: 1587
Joined: Mon Mar 11, 2013 1:37 am

Re: New drug for autism?

Postby FatherOf2 » Wed Mar 20, 2013 9:35 pm

I talked to my neurologist today. She said that there will be a study of Suramin on 9-15 yo autistic children. Only a single dose of suramin will be given. That should minimize serious side effects. I can't get any info on this study even if I contact UCSD directly. There is no info about these trials on clinicaltrials.gov either. So, if you want to participate, you need to find a connection to the researchers directly. It seems to be "by private invitation only" :D

http://clinicaltrials.gov/ct2/results?term=autism&recr=Open

watchtheduck
Posts: 1
Joined: Fri May 30, 2014 3:10 pm

Re: New drug for autism?

Postby watchtheduck » Fri May 30, 2014 4:13 pm

Regarding the drug Suramin, I wouldn't go near this drug with a 10 foot pole. Drugs not only bring in billions, but they also cost a lot to develop. When a drug doesn't pass muster for the purpose it was designed for, some drug developers continue their push to find various means of getting to market with their drugs even when the drug has proven to be harmful. Political clout and the quest for big $ is often the means and motivation for getting a harmful drug to market.

This drug was proven to cause severe bleeding, coma and paralysis during it's testing phases when it was tested for efficacy in the treatment of various cancers, especially prostate cancer, and leads to Guillain-Barre' syndrome when it reaches the 300 mcg/ml level of blood serum. Like Coumadin, it thins the blood. Unlike Coumadin which only stays in the body for a few days once treatment is stopped, Suramin takes 50 days for only half of it to leave the body.

In 1998, Parker-Davis attempted to win FDA approval for this drug which in clinical trials caused more deaths than a placebo drug. FDA advisors voted 10-0 against approval of the Parker-Davis application. What I found interesting is that if you search for this information on the internet it's very difficult, if not impossible to find. Only one source tells the truth about this drug and that is Dr. Otis Webb Brawley, M.D. in his book of "How We Do Harm, A Doctor Breaks Ranks About Being Sick in America." If you "google' that book title, you will find the one source that shares the truth about Suramin and explains in depth about how it evolved through clinical trials with failure after failure. Back on the market now and apparently backed by the FDA, after reading what Dr. Brawley brought to light about it, I can only wonder if the revolving door in D.C. politics is what has allowed a deadly drug to win approval by the FDA a decade after being rejected 10-0 by the FDA board. Should make anyone wary. As I said, I wouldn't touch this drug with a 10 foot pole.

alexsdad
Posts: 134
Joined: Fri Dec 30, 2011 1:31 pm

Re: New drug for autism?

Postby alexsdad » Fri Jan 23, 2015 2:49 pm

Sorry to bring up this old thread. I know there are a few newer posts regarding this research and Suramin but think this is more appropriate thread to continue the discussion.

As some of you already may know, Dr. Naviaux is finally starting a clinical trial soon but he wants only 20 children in the San Diego area. Too bad we don’t live in San Diego because I was seriously considering it. He hopes to have the results by end of 2015 so I guess we will probably hear the outcomes by 2016. He said that he chose Suramin for his research because it was the only drug being tested for its 'antipurnergic' actions when he started the research in 2011. He also said that now there are over 60 related clinical studies - none of them yet for autism, but all aiming at his fundamental disruption in cell-to-cell communication. Please note that this is not about Suramin. This is all about Cell Danger Response (CDR) and Antipurinergic Therapy (APT). I want to point out that Dr. Naviaux stated in his report that "Suramin is a poor drug choice for chronic use because of potentially toxic side effects that can occur with prolonged treatment." He also said there will be many medicines related to Suramin that will develop in the next few years. If his theory turns out to be right, it is going to be huge. It is going to answer many questions that we have discussed on this forum and can potentially help many autistic children and adults and their families.

I initially thought my son would not be a good candidate for APT therapy because we did Purine and Pyrimidine Panel test at Mayo a few years ago and I 'thought' it was reasonably normal. All biomarkers in the panel were within the reference range except for the Uracil level. It was 40 mmol/mol Creatinine and the reference range was <=30 mmol/mol Creatinine. Well, it was slightly higher than the upper limit but I wasn't sure if there was any clinical significance. Our geneticist ordered another test to confirm that it was not Dihydropyrimidine Dehydrogenase Deficiency (DPD Deficiency) and it came back negative. Even before he ordered the test he said that it would be unlikely DPD Deficiency because the Uracil level would have been much higher (in hundreds) for DPD Deficiency. Elevated Uracil is actually quite often seen on autistic children and some people on this forum have posted about it too. Dr. Naviaux explained that the elevated Uracil is a strong evidence that pyrimidine metabolism is altered. Jeez! Why my geneticist never told me about it? Well, he never said the test result was normal. He just said the additional test confirmed my son didn't have DPD Deficiency. Maybe he didn't want to discuss it with me because it would be opening a can of worms and he didn't know what to do about it anyway. We did this test at Mayo but the Organic Acid Profile from Great Plains Lab tests them too. (http://www.greatplainslaboratory.com/it ... est18.html) Interestingly their reference range for Uracil is < 22 mmol/mol Cr. (8 points lower than Mayo's) Anyway if you have done this test, check out the Uracil level and other biomarkers of the Purine metabolism. Purine metabolism is one of the most important metabolism in autism and other developmental delays.

It sounds too good to be true that a single drug normalizes so many problematic biochemical pathways at the same time but it actually makes sense if they all share the same root cause – CDR. The cells are stuck in the defensive mode and refuse to communicate with each other. Even though the initial trigger (i.e., heavy metal or viral infection) is removed later, these cells don’t understand the war is over. APT (Suramin or a similar drug) is a kind of 'armistice' therapy. It basically tells the cells, 'The war is over.' That's the whole point of Dr. Naviaux's theory. I'm curious if this explains the fever effect too. Maybe fever temporarily unlocks the CDR? This is very interesting and I can't wait to see the final outcome of the study.

Since I can’t participate the clinical trial, I'm trying to see if there is any way to trial APT using a safer drug or supplements. Can we put our heads together to figure something out?

Kulkulkan - You mentioned TMT but was that a typo? Did you mean TMP? (Tetramethylpyrazine) Do we want a P2X antagonist rather than a modulator to replicate Dr. Naviaux’s study? What do you think?

I found the herbal medicines listed in the below wiki can work as a purinergic receptor antagonist. I am not sure which one would be a good candidate since they appear to work on different P2X subunits. Can anyone chime in?

http://en.wikipedia.org/wiki/Purinergic_signalling

kulkulkan
Posts: 2075
Joined: Tue Mar 13, 2012 1:37 pm

Re: New drug for autism?

Postby kulkulkan » Fri Jan 23, 2015 5:34 pm

Yes, that was a typo. TMP.

Just checked and our OAT marker for Uracil was 5.7 mmol/mol Creatinine and reference range at that time was less than <16 mmol/mol CR. So never really looked into this marker but will check out in context of above. Thanks.

Here is an excellent overview (perhaps hypothesis) of some of the metabolic features of cell danger response by Dr. Naviaux. Table 1 highlights the potential drug candidates for various indications.

http://www.sciencedirect.com/science/ar ... 4913002390
Highlights
• The Cell Danger Response (CDR) is defined in terms of an ancient metabolic response to threat.
• The CDR encompasses inflammation, innate immunity, oxidative stress, and the ER stress response.
• The CDR is maintained by extracellular nucleotide (purinergic) signaling.
• Abnormal persistence of the CDR lies at the heart of many chronic diseases.
• Antipurinergic therapy (APT) has proven effective in many chronic disorders in animal models.

Abstract
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 in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. 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. These disorders include autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other food and chemical sensitivity syndromes, emphysema, Tourette's syndrome, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney, liver, and heart disease, cancer, Alzheimer and Parkinson disease, and autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis.


Return to “Diet and Biomedical Treatments for Autism”