Thymosin alpha 1 (Thymalfasin/Zadaxin) for auto-immune autism flare-ups?

 

Today’s post is about a drug originally proposed by Wayne State University in the US, but so far approved and widely used mostly in Asia.  China is the big producer/user and Italy is the outlier where it is also used.

 

Therapeutic Developed in United States Benefits Many in Asia

Since Wayne State University gastroenterologist Milton Mutchnick, M.D., first proposed using the hormone-like peptide thymosin alpha 1 to combat Hepatitis B in the mid-1980s, the drug has seen both outstanding success and somber letdown. Overseas, thymosin has become an important tool for fighting Hepatitis B, cancers and infections. Within the United States, its promise remains in doubt decades later.

 

Today we consider repurposing a naturally occurring peptide from the thymus to restore balance/homeostasis to the immune system in people with autism.

It has been well documented in the research (for example by Paul Ashwood at the MIND Institute) that the immune system can be dysfunctional in many people with autism, but in different ways.

Some people with autism suffer from flare-ups when their symptoms get much worse.  These flare-ups can be immune mediated, meaning that the rather complicated pro-inflammatory / anti-inflammatory balance has been disrupted.  A reset is needed.

In some cases, a short course of oral steroids is enough to provide the reset, but often it does not work.

One reader of this blog was proposed by his Italian doctor to try Thymosin alpha 1 shots to treat his son’s autism flare up.  Not surprisingly, living in the UK, he had never heard of Thymosin alpha.

 

 

Source:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747025/figure/F2/

 

 

 

What is Thymosin alpha 1?

 

The following paper provide an excellent explanation:

 

Thymosin alpha 1: A comprehensive review of the literature

 

Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying, enhancing, and restoring immune function. Thymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies, as an enhancer of vaccine response, and as a means of curbing morbidity and mortality in sepsis and numerous infections.

Thymosin alpha 1 has long been recognized as an immune enhancing, immune modulating, as well as an immune restoring agent, and as such it has been utilized in several clinical and research settings. The synthetic form of thymosin alpha 1, thymalfasin, is approved in more than 35 countries for the treatment of hepatitis B and C and as an immune enhancer in several other diseases

 

Thymosin alpha 1 functions as a toll-like receptor (TLR)-9 and TLR-2 agonist in both myeloid and dendritic cells, the professional antigen-presenting cells. By targeting TLRs, thymosin alpha 1 can stimulate the adaptive immune response, which is essential for fighting viral, bacterial, and fungal infections and cancers, as well as stimulation of posterior humoral immunity. Additionally, thymosin alpha 1 can increase levels of IL-2, IL-10, IL-12, interferon (IFN)-α, and IFN-γ. The role of thymosin alpha 1 in stimulating T-cell dependent antibody production is also the reason why it has been considered as a vaccine adjuvant for enhancing response to vaccines.

Thymosin alpha 1 has a wide range of biological activities that range from anti-tumor to immune-modulating properties. The immune response of thymosin alpha 1 is due to its action in elevating the activity of T cell maturation into CD4+/CD8+ T cells. It works to directly activate natural killer cells as well as CD8+ T cells through which it kills virally infected cells. Thymosin alpha 1 has a negative effect on IL-1β and tumor necrosis factor-α, which in turn leads to a decreased inflammatory response and is quite beneficial in conditions such as chronic hepatitis and acute pancreatitis.

  

 Thymosin alpha 1 has a wide range of biological activities. IL: Interleukin; IFN: Interferon; TLR: Toll-like receptors.

  

Thymosin alpha 1 has exhibited the ability to restrain tumor growth, hence its use in the treatment of various cancers. It has anti-proliferative properties which have been exhibited in lung and liver tumor metastases.

Since thymosin alpha 1 is a polypeptide naturally present in the thymus, it plays a fundamental role in the control of inflammation, immunity, and tolerance. Thymosin alpha 1 has an immune-modulating action through its interaction with toll-like receptors. Due to the action of thymosin alpha 1 on other cell types, it is used as a therapeutic agent for diseases with evident immune dysfunction. Clinical trials with thymosin alpha 1 for diseases like DiGeorge syndrome, non-small cell lung cancer, hepatocellular carcinoma, hepatitis B and C, HIV, and melanoma have been conducted and yielded promising results. FDA approved the orphan drug thymalfasin (Zadaxin) for treatment of malignant melanoma, chronic active hepatitis B, DiGeorge anomaly with immune defects, and hepatocellular carcinoma due to its immunomodulatory and anti-tumor effect.

 

  

Thymosin alpha 1 for auto-immune autism flare-ups? 

Thymosin alpha 1 is no wonder drug for autism, but it looks like it has a place in the autism toolbox, for when symptoms take a sharp turn for the worse and you need a reset back to your baseline autism.

If it solves the flare-up, great.  If not, you just move on to the next option. 

 

Conclusion 

Italy does seem to have a different view of medicine.  They are big on the medical use of probiotic bacteria. They have treatments for GI problems that seem to be unheard of in other countries. It is home to the novel idea, that I found appealing, to use nerve growth factor (NGF) eyedrops to prevent dementia.

Italy is also home to the use of Thymosin alpha 1 shots, to reset the immune system after an immune-related autism flare-up.  I think it is a great idea and I doubt it is expensive.

Most readers of this blog are in North America, where Thymosin alpha 1 is not an approved drug. In China, India, Italy and another 30 countries it is widely available. 

As Zadaxin, Thymosin alpha 1, is produced by SciClone Pharmaceuticals in China.  They provide the following summary:

http://www.shijiebiaopin.net/upload/product/2011121219115812.PDF

 

It looks like our readers who have an autism doctor in Italy have some interesting options. 

Wayne State University never sought patent protection for Thymosin alpha 1 in China, which they now regret.

The Semantics of Autism - how the meaning has changed over time

 

A couple of weeks ago I took Monty, aged 18 with ASD, for his Covid booster injection. Since I was accompanying an adult and filling in his paperwork, I thought I should explain why I was needed there. I just said he has autism and prefers to speak English.

Where we live, autism still means severe autism and I for one would be very wary about trying to stick a needle in an unknown person with that diagnosis.

Monty is no problem at all at the doctor or dentist, he has figured all this out.

Moves are afoot to reintroduce the term “profound autism” to describe older children and adults who are severely disabled.

 

The Lancet Commission on the future of care and clinical research in autism (free to access full paper)

Awareness of autism has grown monumentally over the past 20 years. Yet, this increased awareness has not been accompanied by improvements in services to support autistic individuals and their families. Many fundamental questions remain about the care of people with autism—including which interventions are effective, for whom, when, and at what intensity. The Lancet Commission on the future of care and clinical research in autism aims to answer the question of what can be done in the next 5 years to address the current needs of autistic individuals and families worldwide. 

Available to watch on-demand / webinar

 

The term profound autism is not appropriate for young children. It might begin to be useful, with the consent and participation of families, from early school age (e.g., from the age of 8 years) for children with autism and severe to profound intellectual disability or minimal language, given the evidence that these factors are not likely to change. The term might be most helpful in adolescence and adulthood. It is not intended to describe other severe difficulties related to autism that might apply to individuals with extraordinary life circumstances, trauma, family conflict, scarcity of resources, or those with co-occurring mental health problems. We acknowledge that the word profound can have different connotations and other terms might be more appropriate in other languages. For example, in Spanish, the words severo or grave might be more appropriate because of different meanings of profundo (ie, deep).

 

Figure 4 shows the potential effect of differing levels of service, formal recognition of autism, active support, and community adaptation on the outcomes and functioning of the heterogeneous population of autistic individuals.

Societal response and services can optimise outcomes for all people with autism The green line indicates the hypothetical degree to which the environment supports the adaptive potential of autistic people with different cognitive abilities.

 

Many of those who were behind the drive to create the idea of the autism spectrum now acknowledge that the term autism is so broadly applied that it has little meaning.  It looks like they want to go back to the ways things used to be when different diagnoses were used, based on how disabled the person is.

When Kanner and Asperger were studying children in the 1930s, they were mainly interested in those without intellectual disability.

From his landmark paper in 1943, Kanner’s subject #1, later identified as Donald Triplet, grew up, went to College, learned to drive and was a keen golfer.

Today, when people talk of Kanner’s autism or classic autism, they are referring to something very different to much of what Kanner was studying.  They are talking about people with no hope of graduating real high school, let alone driving a car.

Kanner’s autism was not originally profound autism, but nowadays it is.

 

Can you have severe autism and normal IQ?

I would have been one of those saying it is impossible to have severe autism and a normal IQ, but I fully admit that it depends on whose definition you are using.

A retired neurodevelopmental pediatrician called James Coplan has some interesting thoughts.

Coplan wrote a short paper called “Counselling Parents Regarding Prognosis in Autistic Spectrum Disorder”. https://pubmed.ncbi.nlm.nih.gov/10799629/

It is only three pages long.  In one of his videos on his YouTube channel he comments that autism is 130 years behind most areas of medical science, since it is not diagnosed biologically, merely based on observations relative to an ever-moving benchmark, the US DSM (Diagnostic and Statistical Manual of Mental Disorders).

He points out that back in the 1980s under DSM version 3, the only kind of autism was severe autism with MR/ID. So only a few people were diagnosed.  In 1994 version 4 appeared and it included milder autism, with Asperger’s as a sub-type. In 2013 in DSM version 5, Asperger’s disappeared as a sub-type.

Coplan went from working with a rare, but severe disorder to a common but generally much mild one.

 

Coplan considers three variables:

 

·        Atypicality (how autistic you are) occurring along a spectrum from mild to severe.

·        Intelligence, with the centre point being an IQ of 70, the boundary of MR/ID

·        Age

  

Autism of any degree of severity can occur with any degree of general intelligence.

The long-term prognosis represents the joint impact of autism severity and cognitive ability; higher IQ leads to better outcome. 

The observed severity of autism in the same individual varies with age.  Many children with higher IQ do experience significant improvement over time. 

The ideal outcome is child B, in the chart, whose atypical symptoms were always mild and whose intelligence is above cut-off for mental retardation / intellectual disability (MR/ID).  The core features of ASD break up into fragments, which diminish in severity with the passage of time, until only traces of autism remain. 

A less favourable outcome is child A, who has severe autism, plus mental retardation MR/ID.  As time goes by, he continues to exhibit the same level of autism.

Clearly most children will be somewhere in between child A and child B. 

Dr Coplan says that there is little evidence that the prognosis today is different to that in the 1970s or 80s. That suggests little impact from the twenty year surge in expensive ABA interventions in the US.

   

Childhood Schizophrenia 

The original term for what became autism, was childhood schizophrenia, which started being used in the 1920s.

I did mention in an earlier post that I came across an interesting comment written by Michael Baron; back in 1962 he headed the world’s first parent organisation for autism, the UK's National Autistic Society.

Baron’s main point was to highlight how autism has completed morphed in 60 years to a quite different condition.  It is not the same autism. 

When his organisation was originally founded, it was called The Society for Psychotic Children.  That was the name the parents came up with themselves, before later substituting the word Autistic.  

The old name has well and truly been erased from the records.  Definitely not politically correct these days.

Autism may now be a cool diagnosis to some people in 2021, but being psychotic still is not. Perhaps bipolar will be the next cool diagnosis.

Note that the only approved drugs for autism in 2021 are actually antipsychotic drugs!

  

Autism first appeared as an official diagnosis in 1980 

In 1980 the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) includes criteria for a diagnosis of infantile autism for the first time.

In 1994 Asperger’s Disorder was added in DSM-IV as a separate disorder from autism.

In 2013 DSM-5 was published and it combined autism, Asperger’s, and childhood disintegrative disorder into autism spectrum disorder (ASD). 

Hopefully, in DSM-6 there will be more intelligent science-based subdivisions of conditions within autism spectrum disorder (ASD); but, probably not!

 

Autism without impaired speech or cognition

In 2006, before the introduction of Asperger’s as a diagnosis, Ari Ne'eman established the Autistic Self Advocacy Network (ASAN).

These people are a subset of Dr James Coplan’s high intelligence plus mild to severe atypicality.

Many of this group regard intellectual impairment and lack of speech as unrelated to autism.  They see them as just unrelated comorbidities.

The Moms with a case of profound autism at home might counter that the suicidal thoughts that plague the #actuallyautistic people are also not part of autism either, rather a comorbidity.

  

Who is right?

I suppose the science can tell us who is right.

But language is not about science and being right does not really matter.

The meaning of words can change.  The words “gay” and “queer” are no longer usable in their original meanings.

In the school yard, “autistic” is now used as an insult, like all the LGBT words are/were, depending on where you live.

  

Profound Autism

Now let us come back to the proposed definition of profound autism:

·        IQ<50

·        Age>8

·        Severe autism/atypicality

This fits perfectly into Dr Coplan’s framework.

It is the stubborn “block A”.

Far removed from the Elon Musk “block B” type, that was treated in childhood by explaining social cues etc and the result was the symptoms receded into the background; they are only there if you want to see them. 

It looks like some people are desperate for those little cubes not to melt away; they actually find they give them identity and purpose.  Musk just wants to make a lot of money and get to Mars, which looks a better life mission.

 

 

 

You might wonder why you have to wait to the age of 8 for this proposed new diagnosis.  The panel includes Catherine Lord, who conducts the ongoing longitudinal study of autism running now for 20 years. She fully understands that things can change along the way as toddlers grow up.

·       Some people are misdiagnosed with autism at a very early age.  Indeed the well known autism epidemiologist Eric Fombonne found that when you recheck the diagnosis, about a third of people have been misdiagnosed. Doctors over-diagnose to help delayed children access the better services, available to those with an autism diagnosis.  

·       Some toddlers are just late bloomers and after a period of delayed development, do catch up

·        Some people unfortunately have an event in childhood, usually after the age of 5, that causes a (further) regression.  This is what I term “double tap” autism; you survive the first tap, but then along comes the second. The second event can lead to profound disability.

   

Conclusion

You can certainly make the case that the old DSM-IV terminology was much more useful.  People with normal IQ and no speech delay were Aspies and people with low IQ and limited speech had autism.

Many parents do not like now having to say their grown-up child has severe autism, for them autism was sufficient. They see severe as an unnecessary pejorative term.

Once self-advocates tell the world that autism is neither a disorder, nor a disability, it is hard for the wider public not to conclude that autism is nothing more than the new ADHD.  You pay some money, get the diagnosis you want and join the club. 

As Uta Frith, who brought us the well-intentioned idea of autism as a spectrum recently commented, the word autism is now meaningless.

Professor Uta Frith of University College London recently spoke out about autism spectrum disorder (ASD) diagnosis, saying urgent changes are needed in how the condition is diagnosed as it “has been stretched to breaking point and has outgrown its purpose”.

I think one of the underlying problems is that most people do not like any terminology that refers to low IQ.  Don’t dare mention mental retardation. The English language is full of pejorative terms for people with low IQ. Eventually, as their child becomes an adult, some parents start to use the term intellectual disability as a descriptor to distinguish their case from Elon, Greta, Temple Grandin and those cute Netflix depictions.

As Catherine Lord and others have shown from their longitudinal studies, IQ is the best predictor of a better outcomes in adulthood.

There is much in this blog about raising cognitive function and as I have been saying for a while, treating ID/MR is much less controversial than treating autism.

Preventing Miscarriages/Autism using Progesterone? And Sex-Specific Fetal and Placental Responses to Adversity

 

Today’s post returns to the theme of reducing the incidence/severity of future autism and introduces another factor that helps explain why girls have some degree of protection from autism.

The focus today is on female hormones and progesterone in particular.

It does look like hormones can play a role in both triggering and potentially treating some autism, but it is not an area likely to be followed up on in the mainstream.

We have seen previously in this blog that some infertility experts find an association between miscarriage and autism. One US fertility doctor has a prevent miscarriages website and a prevent autism website, because his feeling is that by reducing miscarriage risk, you may also reduce autism risk. He was shocked by how many of his fertility patients have other offspring with autism.

This should really be common sense.

·        In-utero stress increases the chance of a miscarriage

·        In-utero stress increases the chance of autism

The common solution would be to reduce sources of in-utero stress.  Which sounds simpler than it is.

I have previously looked in some detail into therapies that improve outcomes in traumatic brain injury (TBI), because much damage done in a TBI from a car crash, or skiing accident, occurs after the accident, as the brain over-reacts to the trauma and this then causes irreparable damage. Both the female hormones estradiol and progesterone, if given promptly, improve the outcome in TBI.  Another highly neuroprotective drug is Atorvastatin, from my son’s Polypill therapy, which has also been shown to improve outcomes in TBI; we even know how this happens. Atorvastatin, given intravenously, can extinguish a cytokine storm. Cytokine storms even play a key role in severe Covid-19, when lungs and other organs are damaged by the over-response of the immune system.

I was pleased to see that progesterone has recently been adopted as an approved therapy to prevent miscarriages in the United Kingdom.  I am actually really surprised that they were allowed to make the necessary clinical trials.  I would have thought this would be seen as unethical and risky.

 

Progesterone recommended to prevent early miscarriage

One of those behind the Tommy's National Centre for Miscarriage Research research, Prof Arri Coomarasamy, from the University of Birmingham, said  "This is a very significant moment.  We have an intervention that works that can stop a miscarriage. This gives hope to thousands of couples throughout UK. But it's really important to appreciate that only some miscarriages can be prevented by progesterone. There are other causes for miscarriages. We still need to study them. We need to find other effective treatment. About one in four pregnancies ends in miscarriage - the vast majority in the first few months or trimester.” 

 

Progesterone could prevent 8,450 miscarriages a year, finds new research 

PRISM studied 4,153 women with early pregnancy bleeding at 48 hospitals in the UK and found there was a 5% increase in the number of babies born to those who were given progesterone who had previously had one or more miscarriages, compared to those given a placebo.

The benefit was even greater for the women who had previous ‘recurrent miscarriages’ (i.e., three or more miscarriages) – with a 15% increase in the live birth rate in the progesterone group compared to the placebo group.

 

A 5% increase does not sound much.

A 5% reduction in autism incidence probably would not be seen as statistically significant. 5% would not be a very high hurdle for an autism prevention therapy. With a package of therapies, I think you could do very much better. I would consider “good” to be at least a one third reduction in genuine cases. Of course, it would be more complex, since in reality you would be reducing severity of autism. Autism is not binary, more like shades of grey.

 

Would progesterone reduce the risk of future autism?

I do not think we will ever get the answer that question.

Preventing miscarriage is seen as much more important than preventing autism.

The evidence for immediate treatment with progesterone or atorvastatin, after a head injury, has not led to its widespread adoption.  Try explaining that one to Mrs Schumacher (wife of the Formula One racing star, who had a traumatic brain injury while skiing)

The key take away from the PRISM miscarriage study is that progesterone treatment in pregnant women is safe.  It is also inexpensive.

 

Prenatal Hormones in Autism

In a perfect world, you would study hormone levels in pregnant women and find clear associations with autism incidence in offspring. We do not live in such a world.

In the research, hormone levels are all over the place and vary from study to study.

This can be seen as good news, since the range is so wide you can very likely increase the level of certain hormones without any unintended consequences.

  

Foetal oestrogens and autism

Oestradiol, oestrone, oestriol and progesterone each related to autism in univariate analyses after correction with false discovery rate. A comparison of standardised odds ratios showed that oestradiol, oestrone and progesterone had the largest effects on autism likelihood. These results for the first time show that prenatal oestrogens contribute to autism likelihood,

 

When I look at the above graph my conclusion is that the fetal estradiol (oestradiol, in UK English) level is all over the place.  It is nonsense to conclude that high levels are associated with autism. 

 

Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California

Results from this large, population-based study suggest that prenatal levels of the hormones, estriol and a gonadotropin (hCG), as well as MSAFP are associated with altered risks of having a child who later develops autism. Consistently, the risk of ASD was increased at lower levels of uE3; modelled both categorically or continuously, and examining the distribution graphically, the curve seems shifted to the left for cases. Further, the risk of ASD was increased with higher levels of MSAFP, while the associations with hCG were with both low and high levels. Although associations were modest, the fact that our results are based on levels of these prenatal markers measured during a developmentally-relevant period, and account for potential confounders, p

 

Our results suggest that continued investigation of prenatal hormones and possible mechanisms for an association with ASD is warranted. The associations we report were not of a large magnitude, which may make replication of the findings difficult in other studies that do not have access to the large numbers and unique resources we used. The 90th percentiles reflect MoMs of 1.7–2.0, which are not particularly high, but approach prenatal screening risk cut-points currently in use for other conditions (usually 2.0–2.5 MoM). The 10th percentile of uE3 is about 0.75 MoM. Measurement of additional estrogens, as well as androgens, from blood samples collected during pregnancy would be an interesting avenue for future research, if available in large enough studies. In addition, studies of endocrine-disrupting chemicals and genes involved in steroid hormone metabolism may yield further clues to a hormonal etiology for autism. Though modest increases in risk were seen in this large study, converging evidence suggests that ASD has multiple causes, and thus, identifying factors with small associated risks may help to better understand ASD and potential mechanistic pathways.

  

The Prenatal Hormone Milieu in Autism Spectrum Disorder

Though the etiology of autism spectrum disorder (ASD) remains largely unknown, recent findings suggest that hormone dysregulation within the prenatal environment, in conjunction with genetic factors, may alter fetal neurodevelopment. Early emphasis has been placed on the potential role of in utero exposure to androgens, particularly testosterone, to theorize ASD as the manifestation of an “extreme male brain.” The relationship between autism risk and obstetric conditions associated with inflammation and steroid dysregulation merits a much broader understanding of the in utero steroid environment and its potential influence on fetal neuroendocrine development. The exploration of hormone dysregulation in the prenatal environment and ASD development builds upon prior research publishing associations with obstetric conditions and ASD risk. The insight gained may be applied to the development of chronic adult metabolic diseases that share prenatal risk factors with ASD. Future research directions will also be discussed.

 

Female placentas are “superior” to male placentas.  Note the placenta has the same sex as the fetus and yes, it is a binary choice.

  

Sex-Specific Fetal and Placental Responses to Adversity

Fetal growth, development, and HPA axis programming in the setting of obstetric adversity differ by fetal sex (173–175). These sex-specific responses serve as additional mechanisms in which to consider male ASD predominance (see Figure 2). As the placenta is derived from extra-embryonic tissues, the placenta has the same sex as the fetus (178). Evidence suggests that the placentas of male and female fetuses differ in response to adverse prenatal environments through modulation of steroid pathways, placental genes, and protein synthesis (176). Placental growth and structure differ by sex, with male placentas being smaller in size but more efficient at nutrient and oxygen delivery (179, 180). Fetal growth depends upon the limited capacity of the maternal-placental interface to deliver oxygen and nutrients. Thus, greater placental efficiency among males precipitates faster somatic growth while increasing vulnerability to in utero perturbations (179, 181). This may have deleterious neurodevelopmental consequences, as fetal brain development relies on the availability of oxygen and nutrients such as fatty acids, glucose, and amino acids (131, 182, 183). In contrast, female placentas may have superior ability to buffer and adapt to suboptimal prenatal conditions (180).

 

Sex-specific fetal and placental adaptations to maternal adversity. Placentas of male and female fetuses respond differently to mild forms of maternal adversity. In the placenta of female fetuses, multiple changes in glucocorticoid barrier enzyme activity, gene expression, and protein synthesis occur leading to decreased growth (176, 177). This is advantageous as it preserves fetal oxygen and nutrient delivery. In the placenta of male fetuses, minimal changes in gene and protein expression occur, and the male fetus continues to grow incurring increased vulnerability to adverse outcomes (176). 

Figure 3 links heightened in utero stress from inflammation, stressors, and metabolic disturbances to perturbation within the prenatal hormone milieu. Through pCRH stimulation, the placenta upregulates fetal HPA axis activity in response to in utero stress. Subsequently, the fetal adrenal glands increase DHEA(S) synthesis leading to elevated placental estradiol production. Higher placental estradiol and pCRH production promotes HPA axis maturation denoted by fetal adrenal de novo cortisol synthesis. In response to in utero stress, the placental also increases hCG production which stimulates fetal gonadal testosterone synthesis.

 

Linking in utero stress to increased fetal steroidogenic activity and ASD biomarkers at mid-gestation.

 

In utero stress we see raises estradiol in the mother, but also increases testosterone in the males fetus.

The stress hormone, cortisol is elevated in the fetus.

You might imagine that less testosterone and more estradiol would be neuroprotective.

We know that progesterone is neuroprotective and now we know that its use is safe.

 

Conclusion 

Nature does sometimes stumble short of perfection and this is inevitable.  Going too far preventing miscarriages would not be wise, but improving the outlook of a viable fetus looks like a good idea.

Miscarriage is defined as pregnancy loss before 23 weeks’ gestation.

More than 80% of miscarriages occur before the 12th week, and the rate decreases rapidly thereafter.

Chromosomal anomalies cause at least half of these early miscarriages; for example, male fetuses with Rett Syndrome.  This is nature’s way of dealing with a non-viable fetus.  Only girls with Rett Syndrome can survive, since they have one good copy of the the MECP2 gene, males have none. MECP2 is on the X chromosome (girls have XX and boys have XY).

A little helping hand from Progesterone looks like a wise idea.

But, how slowly things move in medical science. The paper below is from 2013.

Use of progestagens during early pregnancy

“During the past 50 years several trials investigated the use of progestagens for the prevention of miscarriage. Actually the therapeutic value of progestagens remains to be established. This might be due to the poor design of the studies which evaluated hormone effectiveness”

 

The issue with using any hormone to prevent/minimize autism is the potential for harm.  This did not seem to worry people in 60 years of trials in miscarriage.

I think we can conclude that progesterone for the prevention/reduction in severity of autism is very likely entirely safe.  Would it be beneficial?

We know that women with Polycystic ovary syndrome (PCOS), a condition in which the ovaries produce an abnormal amount of androgens (male hormones), have an increased chance of producing children with autism.  They might be a good place to start with a clinical trial.

The fact that female placentas give more protection against adversity during pregnancy is interesting and another contributing factor to the lower prevalence of autism in girls.  It is only certain types of autism where girls have protection. In the case of severe autism, girls are more likely to have detectable genetic anomalies than boys, making whole exome sequencing (WES) well worthwhile. It looks like girls are protected somewhat from multifactorial autism, which I think makes sense; they might just end up with some dyslexia or sub-clinical autism.

Multifactorial autism should be the type that you can minimize, by lightening the contributing adverse burdens.  This itself requires a multifactorial approach.