Praise the Lord and pass the Statins - Part 1

If you are not a native English speaker, you may not have heard the praise “praise the Lord and pass the ammunition”.  It originates from a song written after the Japanese attack on Pearl Harbour in 1942.  A warship’s chaplain puts down his bible and mans a gun firing back at the incoming enemy planes saying, "Praise the Lord and pass the ammunition".

According to Wikipedia, the chaplain was Howell Forgy, was aboard the USS New Orleans.

To hear an original recording click here.

In our case the enemy is neuroinflammation, rather than the Japanese.

 

Deborah Fein and Martha Herbert

There are some very good researchers in the field of Autism and these two ladies are on my list of the best.  It looks like this paper was mainly the work of Ms Fein’s colleagues at the University of Connecticut: - Can children with autism recover? If so, How?

The paper is very readable and not science-heavy at all.

One of the explanations put forward for the rare event of recovery, was the possible reduction in neuroinflammation.  This very much fits in with the conclusions so far on my blog;  reduce neuroinflammation and in particular in the cerebellum.

Now we have a brief time-out to introduce you to our new friends, the Statins.

Source: W. Gibson Wood, Ph.D.  Department of Pharmacology, University of Minnesota

Statins

Statins are a class of drug used to lower cholesterol levels by inhibiting an enzyme which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases and statins are therefore used in the prevention of these diseases. Research has found that statins are most effective for treating cardiovascular disease (CVD), with questionable benefit in those without previous CVD, but with elevated cholesterol levels.

Statins act by competitively inhibiting HMG-CoA reductase, the first committed enzyme of the HMG-CoA reductase pathway. Because statins are similar to HMG-CoA on a molecular level, they take the place of HMG-CoA in the enzyme and reduce the rate by which it is able to produce mevalonate, the next molecule in the cascade that eventually produces cholesterol, as well as a number of other compounds. This ultimately reduces cholesterol via several mechanisms.

1.     Inhibiting cholesterol synthesis

By inhibiting HMG-CoA reductase, statins block the pathway for synthesizing cholesterol in the liver. This is significant because most circulating cholesterol comes from internal manufacture rather than the diet. When the liver can no longer produce cholesterol, levels of cholesterol in the blood will fall. Cholesterol synthesis appears to occur mostly at night so statins with short half-lives are usually taken at night to maximize their effect. Studies have shown greater LDL and total cholesterol reductions in the short-acting simvastatin taken at night rather than the morning, but have shown no difference in the long-acting atorvastatin.

2.     Increasing LDL uptake

 

3.    Other effects

Statins exhibit action beyond lipid-lowering activity in the prevention of atherosclerosis. Researchers hypothesize that statins prevent cardiovascular disease via four proposed mechanisms (all subjects of a large body of biomedical research)

1. Improve endothelial function
2. Modulate inflammatory responses
3. Maintain plaque stability
4. Prevent thrombus formation

Statins may even benefit those without high cholesterol. In 2008, the JUPITER study showed fewer strokes, heart attacks, and surgeries even for patients who had no history of high cholesterol or heart disease, but only elevated C-reactive protein levels

 

*****************   Now back to today’s post  *******************

 

Neuroinflammation in the Cerebellum

How hard can it be to find a therapy for neuroinflammation in the cerebellum?  Thanks to Google Scholar, the answer is a few clicks away.

First of all we need to find what other diseases affect the cerebellum or cause inflammation there.  I settled on two completely different cases to investigate:-

1.    Cerebral Malaria 

2.    Traumatic Brain Injury (TBI)

 

Cerebral Malaria (CM) 

First let’s look at what happens in cases of cerebral malaria:-

i) Cognitive sequelae
ii) Speech and language impairment
iii) Epilepsy
iv) Behavior and neuro-psychiatric disorders

Now remember we are looking at malaria, not autism; but this list could just a well be a summary of the effects of autism.

An excellent paper on Cerebral Malaria is: - Cerebral Malaria; Mechanisms Of Brain Injury And Strategies For Improved Neuro-Cognitive Outcome

An emerging area of research is the applications of statins to reduce the neuroinflammation caused by this type of malaria.

Here the secondary action of the statin is important; cholesterol reduction is not relevant.  Here are some highlights:-

·         Cognitive impairment in animals rescued from CM by antiplasmodial drug treatment is abrogated by adjuvant lovastatin administration

·         Lovastatin treatment increases functional capillary density and decreases leukocyte-endothelial interactions

·         Lovastatin protects against blood-brain barrier disruption

·         Lovastatin treatment reduces cytokine levels

·         Lovastatin treatment decreases ROS production

 Read the full report:-  Statins Decrease Neuroinflammation and Prevent Cognitive Impairment after Cerebral Malaria

 

Traumatic Brain Injury (TBI)

It is self-evident that a traumatic brain injury, like a car crash, will lead to neuroinflammation.   The search is on here to find optimal ways to treat this inflammation and achieve an optimal outcome.

 

Here is one paper: - Statins in Traumatic Brain Injury

  

"The use of statins remains a novel therapeutic strategy for TBI. There is robust preclinical data demonstrating the efficacy of statins in acute brain injury models that recapitulate the heterogeneous pathology of clinical TBI. Animal studies have defined mechanisms by which statins may improve outcomes after TBI and should guide statin choice and dosing paradigm for clinical translation."

A more general paper is:- Statins and Brain Dysfunction

and for the older readers:-   Statins: The Role in the Treatment and Prevention of Alzheimer's Neurodegeneration

This should be an interesting paper, but only the abstract is free:-  How do statins control neuroinflammation?

Conclusion

Statins are among the world’s top selling drugs.  With so many people using them, there are of course reported side effects; but as drugs go, the side effects look pretty minimal.  Those at high risk of heart disease, such as those with Type 1 diabetes, are routinely prescribed statins even from a relatively early age.

It has been claimed that autistic people are already at higher risk of heart disease, due to their low level of good cholesterol (HDL) and sometimes higher level of bad cholesterol (LDL). The research is not 100% consistent; but it is very easy to go and check your child's cholesterol.  Holding him still while they draw the blood is another story ....

So it would appear there is one and maybe two very good reasons for autistic people to take statins.


Click below to see Part 2, to decide which statin to choose (there are many).

Statins for Neuroprotection in Autism - Part 2