No Wegovy/Mounjaro moment likely for autism – Lithium etc

 

Semaglutide, marketed under brand names like Wegovy, Mounjaro and Ozempic, is a GLP-1 receptor agonist originally approved for treating type 2 diabetes and more recently for obesity. The global semaglutide market is $27 billion in 2024. The broader market for GLP-1 receptor agonists, which includes semaglutide, is expected to experience significant growth. Analysts project that this market could reach between $150 billion and $200 billion by the early 2030s.

Semaglutide is a dream for pharmaceutical companies. The overweight can forget about diets and exercise; they just need a weekly self-administered dose and wait to lose 20% of their bodyweight in the first year. If they stop taking the drug all the weight will just come straight back, so the patient needs to take the drug for life.

Semaglutide is expensive, but nothing like the price hoped for by those developing elusive autism drugs.

Some obese people save so much money on food it covers the cost of their semaglutide.

Obesity is so damaging that semaglutide should have a transformative impact on healthcare.

On the other hand, the idea that society might increasingly rely on pharmaceutical solutions instead of encouraging lifestyle changes feels rather Orwellian, with a shift away from personal responsibility, fostering dependency on external control. In a society where health problems like obesity are "fixed" by a drug, self-regulation through lifestyle choices will be de-emphasized, giving the impression that human behavior is best managed through a weekly shot.

In the novel Brave New World by Aldous Huxley, published in 1932, people in a highly controlled society all take a drug called soma to feel good, maintain emotional stability, and suppress negative feelings.

 

No Wegovy/Mounjaro moment likely for autism

For people who get their information from social media it appears that such an effortless Wegovy/Mounjaro moment exists for autism. You just send a reply to Facebook post and get a message back telling you where to buy the miracle cure to autism.

Looking at the world of pharmaceuticals many parents hoped that Suramin would be the cure to autism.

Recently I saw yet another rather misleading headline:

Lithium restores brain function and behavior in Autism

Really, what it should say is:

Lithium may restore brain function and behavior in Autism caused by Dyrk1a mutation if given while a baby.

 

Here is the article.

Lithium Restores Brain Function and Behavior in Autism

Lithium, a drug widely used for bipolar disorder, may also treat autism spectrum disorder (ASD), according to new research. The study found that lithium restored brain function and reduced behavioral symptoms in mice with Dyrk1a gene mutations, a known ASD risk factor.

Administered during the juvenile period, lithium normalized brain size, improved neural connectivity, and eased anxiety and social deficits, with benefits persisting into adulthood.

This breakthrough highlights lithium’s potential to address core ASD mechanisms through its action on Kalirin-7, a molecule critical for synaptic function. The findings underscore the importance of early intervention and targeted treatments for ASD.

The team discovered that lithium’s therapeutic effects are partly mediated through its action on Kalirin-7, a molecule essential for synaptic structure and function.

By targeting this molecule, lithium helped to restore balance in the brain’s signaling networks, addressing one of the core mechanisms of ASD.

“This is an exciting breakthrough,” said Dr. Roh Junyeop, a senior researcher and co-first author of the study.

“Dyrk1a mutations disrupt neural connectivity, much like a traffic jam or roadblocks in a city. Lithium helps to clear the congestion, restoring smooth communication between neurons.”

Director Kim Eunjoon emphasized the potential impact of these findings, stating, “Our research shows that lithium, a widely used drug for bipolar disorder, could also serve as a treatment for ASD. The fact that its effects persist long after treatment ends underscores the importance of early intervention during critical developmental windows.”

This study, published in the journal Molecular Psychiatry on December 5, not only paves the way for new therapeutic approaches for ASD but also underscores the critical importance of early diagnosis and intervention.

It offers hope to families and individuals affected by ASD, suggesting that targeted treatments may one day reduce the burden of this complex disorder.

 

Too little Dyrk1a leads to small brains, autism and low IQ. In Down syndrome there is too much Dyrk1a expression and this is a contributing factor to low IQ. You need just the right amount of Dyrk1a for optimal brain development and then a higher IQ. Too much Dyrk1a also leads to Alzheimer’s which is why there can be early onset in those with Down syndrome.

Don’t give lithium to someone with Down syndrome.

 

GSK-3β and Dyrk1a

In previous posts we did look at something called GSK-3β, which plays a role in autism.

GSK-3β  and DYRK1A  are two enzymes that play significant roles in regulating cell signaling, neurodevelopment, and brain function. They also interact with each other. Both play a role in the Wnt signaling pathway, which is disturbed in much autism and some cancer.

 

Lithium in Autism

Lithium carbonate is a prescription drug used to treat bipolar.

Lithium orotate is an OTC product that some people do use to treat autism. The dosages are usually very low compared to what is used in bipolar.

It is not uncommon to be diagnosed with bipolar and autism.

 

Is Lithium a game changer for Autism?

While some people may well benefit, the usage to date shows that lithium is not a game changer for most autism.

 

Mebendazole for some Autism and indeed Down syndrome

I did propose years ago that Mebendazole/Vermox, the cheap drug used to treat pinworms in children, might have potential to treat some autism. Mebendazole is a Wnt inhibitor (the opposite of Lithium). I did receive a message recently that Mebendazole was beneficial in one reader’s son. Not much Mebendazole is absorbed into the bloodstream but you can maximize it by taking it with a fatty meal. It does cross the blood brain barrier.

Mebendazole has been shown to inhibit DYRK1A in laboratory settings, which could potentially address the effects of DYRK1A overexpression seen in conditions like Down syndrome. Since Down syndrome is diagnosed very early, treatment could start very early, which is critical to optimize the developing brain.

 

Mebendazole - Wnt Inhibition and other effects

Mebendazole is known to inhibit components of the Wnt signaling pathway. Inhibition of Wnt could potentially normalize overactive or dysregulated pathways, leading to more balanced dendritic spine dynamics in individuals with autism. In autism, there is often an imbalance in dendritic spine formation and pruning, leading to either excessive or insufficient connectivity. Modulating Wnt signaling could potentially restore this balance, improving synaptic function and related behaviors.

Mebendazole has been shown to have anti-inflammatory properties. Since neuroinflammation is often elevated in autism, this could indirectly improve symptoms.

Mebendazole also stabilizes microtubules, which are critical for intracellular transport and synaptic function. This might indirectly benefit neuronal communication in autism.

  

Conclusion

Autism is far more complicated and heterogeneous than obesity so sadly there can never be a simple Wegovy/Mounjaro moment.  Best not to listen to Autism Moms telling you otherwise on Facebook.

On the plus side there are numerous partially effective therapies, sitting on the shelf in the pharmacy that do benefit specific types of autism. You just have to find what works in your very specific case.

I was recently asked a German mother if I have a spreadsheet listing all the possible therapies, what the benefits are, and in what order to try them. It is a very rational request, but there is so much variation that this would not be a simple task.