tag:blogger.com,1999:blog-655962722302095847.post7232581638026339022..comments2024-03-29T07:12:51.030+01:00Comments on Epiphany: Propranolol, Autism and Sodium Ion Channels Nav1.1, Nav1.2, Nav1.3 and Nav1.5Peter Lloyd-Thomashttp://www.blogger.com/profile/10173383229834614994noreply@blogger.comBlogger43125tag:blogger.com,1999:blog-655962722302095847.post-16452483074004841022023-12-25T21:56:38.855+01:002023-12-25T21:56:38.855+01:00Ula, yes it is loss of function of SCN2A that can ...Ula, yes it is loss of function of SCN2A that can lead to autism.<br />There are many drugs that block the Nav1.2 ion channel enclosed by your gene, but you would likely think that you want the opposite, a channel opener. But, as if often the case in autism, timing is very important.<br /><br />During early development, Nav1.2 is localized along the axon length in cortical pyramidal neurons. As development continues, Nav1.2 is gradually replaced by Nav1.6 along the axon, and Nav1.2 expression becomes localized mainly to the axon initial segment.<br /><br />This shift to Nav1.6 occurs by 2 years of age, and has already occurred.<br /><br />In contrast, in cerebellum, Nav1.2 expression persists at a much higher level in adulthood. This suggests the channel may play different roles in the different regions of the brain.<br /><br />From the paper:<br /><br />Progress in Understanding and Treating SCN2A-Mediated Disorders<br /><br />"An additional consideration is the reversibility of the symptoms. SCN2A expression begins early in gestation [8], and channel dysfunction may alter brain development. In keeping with this concern, computational modeling of loss-of-function variants suggests that neuronal excitability is restored in the mature brain as NaV1.6 replaces NaV1.2 as the critical channel underlying action potential generation at 2 years of age [24]. Despite this proposed functional compensation in action potential initiation, symptoms of ASD/ID continue beyond this age. It will therefore be critical to understand the physiological changes that persist within the brain in individuals with loss-of-function variants and whether these changes can be rescued by restoring NaV1.2 function.<br /><br />Clearly research is in the early days.<br /><br />A useful source of information can be found here.<br /><br />https://www.scn2a.org/<br /><br />I would suggest you treat your child as just idiopathic autism and go through all the possibly effective therapies.<br /><br />I would trial bumetanide before propranolol.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-5545809087409582352023-12-24T11:56:27.877+01:002023-12-24T11:56:27.877+01:00Hi Peter. I have discovered recently that my son h...Hi Peter. I have discovered recently that my son has SCN2A gene. From what I’ve read the gene can be expressed as ‘gain of function’ which is associated with an epilepsy, and the ‘loss of function’ which is connected to autism and ID. My son doesn’t have an epilepsy so I am assuming loss of function expression.<br />Would propranolol be usefull in such a case? From what I read sodium channel blockers should be avoided. Any other treatments that could help?Ulanoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-70547808240931885892021-12-07T11:14:46.795+01:002021-12-07T11:14:46.795+01:00Both vitamin C (ascorbic acid) and propranolol can...Both vitamin C (ascorbic acid) and propranolol can be beneficial in some autism. Restricted diet can lead to low vitamin C which will then cause many issues. Propranolol works well for a specific kind of anxiety, many people use it before exams and driving lessons. Some people with autism do benefit, others do not.<br /><br />I am not surprised that FOPCON is effective in some people with autism.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-30766198935398895812021-12-07T00:47:34.079+01:002021-12-07T00:47:34.079+01:00Hi Peter, today I found this news about a survey a...Hi Peter, today I found this news about a survey at the Federal University of Mato Grosso on the use of a drug developed for fibrodysplasia ossificans progressive in children with autism. In the article they don't mention which drug, but searching for the names of the doctors involved I arrived at FOPCON (combined formulation of 14 mg of propranolol and 250 mg of ascorbic acid). Follow the news link (video in Portuguese, unfortunately).<br /><br />https://noticias.r7.com/jr-na-tv/videos/pesquisadores-desenvolvem-medicamento-que-pode-dar-mais-qualidade-de-vida-a-pessoas-com-autismo-04122021Anonymoushttps://www.blogger.com/profile/06543828876835871542noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-54667696115692505082020-03-10T17:34:44.956+01:002020-03-10T17:34:44.956+01:005mg twice a day5mg twice a dayRizahttps://www.blogger.com/profile/17553698982629217172noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-5539032427264531652020-03-09T19:03:46.999+01:002020-03-09T19:03:46.999+01:00Riza, ask the lady what dose she uses. I would cal...Riza, ask the lady what dose she uses. I would call 5mg a low dose.<br /><br />I think it will only benefit a small number of people.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-5773439573122585502020-03-09T18:18:10.725+01:002020-03-09T18:18:10.725+01:00Hi again
Someone on the FB posted
"Low dose P...Hi again<br />Someone on the FB posted<br />"Low dose Propranolol has been the best intervention for us"<br /><br />She continues, "Resolved failure to thrive, anxiety and ocd significantly decreased, hypersexual behaviour almost completely stopped, immune markers improved and others"<br /> <br />Will it be affective like 5mg of propranololRizahttps://www.blogger.com/profile/17553698982629217172noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-25060194470978173692020-03-08T19:55:50.451+01:002020-03-08T19:55:50.451+01:00The limiting factor on the dosage is heart rate an...The limiting factor on the dosage is heart rate and blood pressure. This you can measure at home. You need to make sure these stay within the normal range.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-31512474717887064652020-03-08T17:25:02.924+01:002020-03-08T17:25:02.924+01:00Hi
I tried .10g propranolol on my son
It almost ...Hi <br />I tried .10g propranolol on my son <br />It almost stopped potty accidents increased his attention span <br />Though couldn't find any congnitive gains <br /><br />Do you have any idea about the optimal dosage for propranololRizahttps://www.blogger.com/profile/17553698982629217172noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-30516456265028144862017-11-14T16:57:28.919+01:002017-11-14T16:57:28.919+01:00Tanya, I do not know the answer.Tanya, I do not know the answer.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-82328449849504628572017-11-14T15:56:16.168+01:002017-11-14T15:56:16.168+01:00Peter, hmmm propranolol to treat PTSD?? I'm li...Peter, hmmm propranolol to treat PTSD?? I'm listening..... A few yrs ago, maybe a little more, a friend of mine got her son in to see Dr Frye. He then had a place for propranolol in his tx plan for mito - to first calm down the adrenals. Do you know if this is a standard practice in mito tx?Tanyahttps://www.blogger.com/profile/01489962611979985947noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-69868269392661762262016-03-24T06:53:10.126+01:002016-03-24T06:53:10.126+01:00re: FRAX486
question to: alli9 February 2016 at ...re: FRAX486 <br />question to: alli9 February 2016 at 17:27<br />I wonder what are the safety data available for FRAX486?Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-67195114509373219622016-02-15T15:13:40.185+01:002016-02-15T15:13:40.185+01:00Another organization that funds autism research (i...Another organization that funds autism research (in Canada):<br />http://www.azrielifoundation.org/neurodevelopment/<br /><br />J.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-13120610670462544232016-02-15T10:33:18.883+01:002016-02-15T10:33:18.883+01:00Sodium Butyrate is very interesting. I used to do ...Sodium Butyrate is very interesting. I used to do that for my son but switched to a combination of inulin, potato starch, and barley flour in a shake I give my son everyday with the idea of the gut bacteria producing the butyrate via the various sources of soluble fiber. My son won't do pills and sodium butyrate literally smells and tastes like puke so it is hard to mask. Do you do the sodium butyrate because it is an HDAC inhibitor or else is it supplemented to help keep the gut healthy?<br /><br />L-Theanine paradoxically (pre-Bumetanide) caused extreme mood swings and aggression. My best guess was that the glutamic acid that it metabolizes to was tipping the scales with regards to excess glutamate (normally the excitatory amino acid transporter in the BBB keeps influx rates pretty low) as theanine rapidly crosses the BBB but once in the brain it can be metabolized back to glutamic acid.Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-1909185046647783702016-02-15T10:15:35.777+01:002016-02-15T10:15:35.777+01:00Alli, so where are you acquiring your J147 ? If i...Alli, so where are you acquiring your J147 ? If it works in autism, tell the Simons Foundation, they are not profit seeking. Also according to Nat, there is another very wealthy donor interested to fund autism.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-87235345093848249252016-02-15T10:14:52.688+01:002016-02-15T10:14:52.688+01:00This comment has been removed by a blog administrator.Anonymoushttps://www.blogger.com/profile/05200274131938112861noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-84921387126299506882016-02-15T10:11:17.970+01:002016-02-15T10:11:17.970+01:00This comment has been removed by the author.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-5234661769617667502016-02-15T01:27:50.713+01:002016-02-15T01:27:50.713+01:00This comment has been removed by a blog administrator.Anonymoushttps://www.blogger.com/profile/05200274131938112861noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-11330527610398173982016-02-14T21:55:39.380+01:002016-02-14T21:55:39.380+01:00Hi D&G, J147 is an experimental drug.
https:/...Hi D&G, J147 is an experimental drug.<br /><br />https://en.wikipedia.org/wiki/J147<br /><br />Curcumin is interesting, it is available in many forms that try to improve its bioavailability. It is worth a trial and many people with ASD do take it.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-87674493574749494812016-02-14T11:06:34.381+01:002016-02-14T11:06:34.381+01:00Hi Peter,
Have you come across J147? Alli appears...Hi Peter,<br /><br />Have you come across J147? Alli appears to have had a 'cognitive enhancing' revelation with its precursor curcu in. I see parallels with your Bumetinide revelation.<br /><br />Has anyone else tried Longvidia Curcumin? Is it worth a trial?<br /><br />Regards,<br />D&G<br />Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-15058371027168053392016-02-13T19:01:48.229+01:002016-02-13T19:01:48.229+01:00Hey Peter,
I really enjoy your blog and informat...Hey Peter, <br /><br />I really enjoy your blog and informative posts but there is also some gold in your comment section. The problem is it's really hard to search and navigate through previous comments. Maybe you might want to install a forum? It would make it a lot easier for readers to post, respond and keep track of messages. <br /><br />Keep up the good work!Anonymoushttps://www.blogger.com/profile/12492640542289353042noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-18200835563060613452016-02-12T21:14:10.024+01:002016-02-12T21:14:10.024+01:00Nat, Thank you very much for sharing your experien...Nat, Thank you very much for sharing your experience with carnitine. I don't know what to say, I haven't trialed it for myself yet. May I ask how long you had been using it before you noticed aggressive behaviour and how much? We use it for 10 days and raised the dose to 2gr/day. I also combine it with Nac for irritability and seems to work. <br />Once again thank you for keeping me informed.Anonymoushttps://www.blogger.com/profile/16138974464162606874noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-80327102966306167712016-02-12T13:51:48.884+01:002016-02-12T13:51:48.884+01:00Thanks for the explanation.
I took my data from t...Thanks for the explanation.<br /><br />I took my data from the Clinical Trials.gov website.<br /><br />https://clinicaltrials.gov/ct2/results?term=curemark+CM-AT&Search=Search<br /><br />Faecal chymotrypsin was used as reliable index of exocrine pancreatic function. When I went to order the test, I was told the test is not so good and there is a more reliable one (elastase-1). I did the newer test and it was all normal.<br /><br />For years there has been an treatment for lack of pancreatic enzymes:-<br /><br />https://www.creon.com/CFPatients/WhatIsCreon<br /><br />I wonder if CM-AT is any better than creon.<br /><br />It looks like no test is totally reliable, here they compare the older chymotrypsin with the newer elastase-1, that I used.<br /><br />Fecal elastase-1 determination: 'gold standard' of indirect pancreatic function tests?<br /> <br /><br />http://www.ncbi.nlm.nih.gov/pubmed/11589385<br /><br />"Neither test is suitable for screening, as they provide a pathologic result in roughly half of 'non-pancreas' patients."<br />Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-46947316248961370382016-02-12T01:36:31.197+01:002016-02-12T01:36:31.197+01:00I seriously blame Baron-Cohen and the whole neurod...I seriously blame Baron-Cohen and the whole neurodiversity thing. They've set autism research back 10 years, at least. I like Jonathan Mitchell, but people say that he wants a cure because his parents "made him feel bad about his autism". Whatever. Don't get me started. Joan Fallon actually says in a video that they released that they passed all their endpoints for the low chymotrypsin trial. I think it's on a TedTalk, the Power of Disruption, they met their clinical endpoints for CM-AT, and they started the NDA. For some reason that I can't fathom, instead of having the FDA approve CM-AT for kids with low chymotrypsin, they are having to do ANOTHER clinical trial for all levels of chymotrypsin to see if it helps irritability. So, apparently this is what a fast track looks like...I remember seeing expectations that the "drug" would be approved by 2012. I really hope I don't get in trouble for this, but my kid is in that trial. Suffered through 3 months of getting placebo (they get burn reactions on their mouths that I'm having to counteract that he didn't have during that 3 months). He's been on "drug" since late December. And, admittedly, it's been a little like hotwiring a car. The cars lights come on and the engine starts to turn over, then the wire disconnects, and the car dies. But, I can call his name from anywhere in the house and he immediately responds. He has days when he is so connected with us. But, on the disconnected days he can be kind of frustrating because you've gotten to enjoy the good days. After a month on "drug", his chymotrypsin level is at a 10.4. Still considered low, even though she says in her TedTalk that anything above a 10 was considered in the "normal range". The clinical trial actually set the ceiling for low at 12.6. He is talking tons more. He can sit and play a game with his older brother and me. He wants me to play with him at the pool. The frustrating thing to me right now is no one is enrolling in this trial. Yeah, it's not a cure, but his behavior is tons better. So, that goes back to the neurodiversity movement and the whole "we don't want a cure" attitude. I just want the FDA to approve it so I don't have to worry about it going the way of Arbaclofen. To me, the better way to do this is to determine the side effects of the drugs, determine if they are, at least, relatively safe. Let doctors prescribe what's available and see what works for each individual kid. Maybe drug companies can start looking at the medical workups for the kids that respond to certain drugs and back into better solutions that way. I just think we need to start thinking outside the box.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-43908714393133638852016-02-11T22:49:06.718+01:002016-02-11T22:49:06.718+01:00Aren't they finishing phase III for autism thi...Aren't they finishing phase III for autism this year? Btw they are recruiting for a manufacturing director, according to their website 'hoping to start large scale production' soon. As their autism trial will be the first one to cross the finish line this is saying to me they are willing to bet good money on CM-AT getting FDA approval. Natnoreply@blogger.com