UA-45667900-1

Sunday, 12 May 2013

Statins for Neuroprotection in Autism - Part 2

I suggest you start by reading Part 1.  Click here for Part 1



Choice of Statin
 
Some statins are soluble in fats/lipids (lipophilic) and some are more soluble in water.  In order to cross the blood brain barrier (BBB) to reach the cerebellum and the Purkinje Cell Layer (PCL) a lipophilic statin will be required.  There is a choice of three: - atorvastatin, lovastatin, and simvastatin.  These are also among the most commonly prescribed for cholesterol reduction and so are widely available and inexpensive.

I chose atorvastatin.  Some statins are derived from fungi, but atorvastatin is synthetic.  Lovastatin and simvastatin are pro-drugs, whereas atorvastatin is already in an active form straight out of the box. Absorption of atorvastatin decreases when taken with food.  Due to its long half-life, atorvastatin can be administered at any time of day.

Atorvastatin is approved for use in children as young as 10 and in the US is prescribed to children as young as 5.

Atorvastatin, originally made by Pfizer under name Lipitor, is the best-selling drug in the history of the pharmaceutical industry.  It came off patent recently and so the price has collapsed to a very reasonable level.

In some countries the low dose forms are available over the counter, without a prescription.

 

More Related Research

The research effort into degenerative conditions like Alzheimer’s disease (AD) is far more prolific than into autism.  The closest research to my hypothesis that statins will “perk up the Purkinje cells” is this study:-


  

Fragile X syndrome

Fragile X syndrome is a genetic syndrome that leads to autistic behaviours.  About 5% of the cases defined as autism are due to this genetic flaw.  It also results in certain physical differences, namely:-
  • Large, protruding ears (one or both)
  • Long face (vertical maxillary excess)
  • High-arched palate (related to the above)
  • Hyper extensible finger joints
  • Hyper extensible ('Double-jointed') thumbs
  • Flat feet
  • Soft skin
  • Hypotonia (low muscle tone)
  • single palm crease (crease goes across entire palm)

 At MIT researchers have found that the statin Lovastatin “can correct Fragile X syndrome”.
 
I presume what is actually happening, is that in Fragile X there is also neuroinflammation and this has been reduced by the statin, rather than correcting the syndrome.
  

Retts Syndrome

Retts syndrome is another genetic disorder that causes regression and autism-like behaviours.  It affects mainly girls, because male fetuses with the disorder rarely survive to term.  The prognosis is not good.

Research is underway with statins and currently shows that statins improve symptoms of Rett syndrome in mice.

 
Statins and depression

A large study of patients with heart disease examined the difference between those on statins and those not.  Very interesting was the finding that those on statins had better mental health (i.e. less depression).


Statins: Mechanisms of neuroprotection

A very thorough presentation of the effect of statins and their possible mechanisms along with a review of their use in Alzheimer’s, Parkinson’s, Multiple Sclerosis and strokes, is in the excellent paper:-  Statins: Mechanisms of neuroprotection


 The anti-oxidant effect of statins

A study called The anti-oxidant effect of statins, looks very interesting, but only the abstract is freely available.  Here is the summary:-  

"A number of recent reports have shown that statins may also have important anti-inflammatory effects, in addition to their effects on plasma lipids. Since inflammation is closely linked to the production of reactive oxygen species (ROS), the molecular basis of the observed anti-inflammatory effects of statins may relate to their ability block the production and/or activity of ROS. In this review, we will discuss both the inhibition of ROS generation by statins, through interference with NAD(P)H oxidase expression and activity, and the actions of statins that serve to blunt the damaging effects of these radicals, including effects on antioxidant enzymes, lipid peroxidation, LDL cholesterol oxidation and nitric oxide synthase. These antioxidant effects of statins likely contribute to their clinical efficacy in treating cardiovascular disease as well as other chronic conditions associated with increased oxidative stress in humans."

 
Conclusion
 
Given the minimal side effects, that was more than enough evidence for me to start some primary research of my own. Step one was to try atorvastatin myself. 

My hypothesis is that atorvastatin will reduce autistic behaviours and that the mechanism is the reduction of neuroinflammation in the cerebellum and particularly in the Purkinje Cell Layer (PCL).  I believe that this will be valid regardless of the type of autism. 

The beneficial secondary effect will be reduction in LDL cholesterol, which is typically elevated in cases of autism.

 
Click here for  -  Statins Part 3



 

6 comments:

  1. Hi Peter,
    it is now almosta year since you published your thoughts about statins and ASD here - how do you see this theme today? Did you experiment with atorvastatin - and if so, what results?
    I am father of 7 year old boy with ASD, myself taking atoris and considering trying it in my son.
    Just came across with article on statins and MS - Lancet published study reported here http://www.bbc.com/news/health-26630025
    Statins 'may help control multiple sclerosis'
    Thought it may be of interest to you too.
    Many thanks for response and best regards from the banks of blue Danube in Central Europe,
    Juraj - mesik@changenet.sk

    ReplyDelete
  2. The result of 10mg Atorvastatin daily is positive. It is a small change, but it is definitely there. If I stop the statin, the positive change is lost within a day or two. The change is subtle it relates to releasing some internal inhibitions; in other words there are things your son wants to do but feels blocked from doing. This was very marked on our case because the after taking the first statin, he started to spontaneously play the piano for the very first time, outside of a lesson, and hug people. He has played every day since. If I stop the statin, he says things like “I want to go downstairs” but remains stuck at the top, as if an invisible hand is stopping him. I suggest you measure you son’s cholesterol before starting. If it is elevated, as is highly likely, you have another reason to try the statin

    ReplyDelete
  3. I have Verapamil and Atorvostatin now to try it and am a little apprehensive so I read through these two posts. We are having really great results following your polypill so far. Today for the first time ever- my son reported about his school activities. He has no conversational language but can use 3-5 word scripts to get his needs met. I asked "what did you do at school today" and he said "playground" and "baseball". I checked with his teacher - yes he did play baseball this morning! Happy tears today - thank you Peter

    ReplyDelete
    Replies
    1. That is great.

      I would suggest you try Atorvastatin first. If it works as for my son, there will changes within 24 hours, although you may need longer to convince yourself. A short trial of this drug for a few days is all you will need. If there is no effect, then stop. If it makes things worse, then you would have likely found a mitochondrial dysfunction. I think you will either see no effect, or a good effect.

      Verapamil was my treatment for summertime raging. I was curious to see the effect (or not) in others, and was surprised that most people trying it also find it effective. In my son, testing in winter would show no effect.

      Delete
  4. Hello Peter,

    Very good articles, and written nicely. I Have a son who is 18 years old now. He was fine as a baby (everything went normal), although he had diarrhea once in a while, but when he had diarrhea at 9 months old for several days, we thought this might be due to teething or because of picking things from the floor and eating. He was treated with antibiotics a few times. He later became alright. He never had any leaky guts, but he started loosing his language around 16-17 months (he used to speak quite a few words, he had his MMR shot along with the other 3 shots when he was 15 months old, and gave him Tylenol drops immediately since the pediatrician always suggested to give Tylenol immediately after the shots to avoid the pain/fever) and started calling everything and everyone as mom. Other than this, we did not see any other major changes like leaky guts, spinning, seizures, lining up or hurting himself in the beginning. He was very good with puzzles and legos. Even the pediatrician did not recognize that he has a problem. When he was 3 years old, he was diagnosed as PDDNOS (I do not have anyone like this in the family, did not know anything about this before). Later he learnt language (speaks well), started reading early (do not have good comprehension), a very good speller, a calendar savant. As he is getting older, the echolalia is increasing significantly (blurting dialogues continuously from TV shows, not aware of the surrounding or people), very bad temper tantrums, very lethargic, hurts himself, never wants to study/do house chores, very short-tempered, worries a lot for teeney-weeney things, no focus or motivation, easily get offended and then cut clothes, game consoles etc /delete all the important documents, photos, homework etc/throw homework, games, clothes etc, doing sort of okay in school. Since his case is more like a regressive autism, do you see this one as AMD? I would highly appreciate some advise how to treat him. We have tried several therapies/medications (including sulphoraphane, low dose naltroxene etc. I cannot remember all of them. He takes multi-vitamin, vitamin D, fish oil, Biotin, and a very low dose of beta-blocker to keep him calm). I sincerely thank you for all the help.

    ReplyDelete
    Replies
    1. My suggestion is to start with NAC, it is inexpensive and effective in the great majority of cases. Assuming your son can swallow pills, just buy the cheaper capsules (usually 600mg). Since he is older, I suggest 4 or 5 capsules a day. It works best if your spread them out throughout the day. You can also use NAC Sustain, which is delayed release.

      This should rapidly affect/improve his behavior. If it does not then it might well be AMD. But I think the NAC will work.

      Also, start to keep a diary of his tantrums and self injury. Try and see if there is any pattern. For my son triggers include allergies and tooth pain.

      Try the NAC for a week and then let me know what happens, then we can take things further.

      Delete

Post a comment