Drugs

New Drug For Autism And Fetal Alcohol Syndrome In The Works; Could It Change Our Understanding Of These Disorders Forever?

Social Disorders Can Start in the Womb, But May Be Treated By New Hormone Therapy
A new study identifies thyroxine, a hormone absent during both autism and fetal alcohol syndrome, as a potential treatment for the two disorders. Fetus| lunar caustic/flickr

Brain disorders often develop well into adulthood, but they can also occur in the womb.

Fetal alcohol spectrum disorder (FASD) and autism spectrum disorder (ASD) are two social and behavioral disorders stemming from altered neurological development, often beginning in the womb. FASD refers to the spectrum of disabilities and disorders caused by maternal consumption of alcohol during pregnancy, and ASD refers to a social or behavioral disorder related to delays in cognitive development that affect communication skills and social interactions.

FASD and ASD appear to be caused by similar occurrences on the molecular level during a woman's pregnancy. While one disorder may not lead to another, they are linked by the mechanism through which they occur. Both change the expression of genes that allow the body to make thyroxine, a hormone that regulates metabolism and is essential for proper development.

The researchers used this commonality to their advantage in experiments. In rats, where some were affected by ASD and others FASD, the researchers established a relationship between the disorders and the expression of the genes that stimulate a thyroxine release. They also found that male rats, exposed to ASD or FASD, were most affected when it came to thyroxine levels.

When FASD rats were given alcohol, the levels of their thyroid-stimulating hormone (TSH), the hormone that stimulates the release of thyroxine, were very low. However, if researchers gave the rats increasing amount of thyroxine, their TSH levels would normalize, and they would begin making thyroxine themselves. This finding is key because it indicates that the mechanism by which FASD can happen is reversible and therefore treatable.

Similarly, when ASD rats were examined, they too had low TSH levels. Researchers found that genes in the brain that are meant to make TSH were not present, or otherwise turned off, so their TSH levels were also low. Upon the addition of TSH, the genes in the brain turned on once more, and started making TSH and therefore thyroxine.

The findings of this study are promising. In the experiments where thyroxine was added and helped increase TSH levels, the behavioral and social interactions were observed. Both rats, with FASD and ASD, showed more normal social interactions with other rats after treatment with thyroxine. The treatment thus appears to have reversed the deficit hormonally and genetically.

R. Thomas Zoeller, Ph.D., a professor of biology at the University of Massachusetts Amherst, said, "Because of the overlap in behavioral deficits between FASD and ASD - both in humans and in animals - the current findings are very important to both of these fields. There are several studies showing that FASD children exhibit similar behaviors to children with ASD, so the authors of the current study are quite right to make these comparisons experimentally."

"In addition, we know that thyroid hormone has similar effects on humans and animals, so there is high confidence that the studies described here are relevant to human - and public - health. Because ASD is increasing in incidence and prevalence, the current studies are also important because it points to a potential biochemical marker - thyroid hormone - that could be used to identify children that may be at risk for ASD."

Zoeller added that caution must be used in finding parallels between rat and human treatment with thyroxine.

"These are important new experimental findings that will not be fully understood for some years," he said. "However, they will be the basis for a more effective research direction that could ultimately help children with these conditions. Results should encourage pregnant women - or women considering starting a family - to ensure that her thyroid gland is working properly. Moreover, the study might suggest that pregnant women have thyroid tests done at her initial prenatal checkup. However, the use of thyroid hormone supplementation during pregnancy must be very carefully managed because other studies show that an overdose of thyroid hormone could also produce adverse effects."

Dosages between rats and humans can be very different and high levels of thyroxine can be dangerous.

This finding on thyroxine is nevertheless significant, as it could provide treatment options in the future for people with ASD and FASD, both of which are currently untreatable.

 

Source: Tunc-Ozcan E, Ullman TM, Shukla PK, Redei EE. Low-Dose Thyroxine Attenuates Autism-Associated Adverse Effects of Fetal Alcohol in Male Offspring's Social Behavior and Hippocampal Gene Expression. Alcoholism: Clinical and Experimental Research. 2013.

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