Drug in trials for one autism-linked condition may worsen another

Suppressing slumber: The drug rapamycin worsens sleep in both fragile X and typical mice. unoL / iStock

Source: [Spectrum,  | January 26, 2018]

The drug rapamycin, which is in clinical trials for tuberous sclerosis (TSC), exacerbates features of fragile X syndrome, another condition related to autism, a new study suggests1.

Rapamycin increases anxiety, shortens sleep and worsens social skills in a mouse model of fragile X syndrome, the researchers found. And the drug does not alleviate seizures or cognitive problems in these mice.

The work should serve as an alert to researchers testing rapamycin for conditions related to autism, says lead investigator Carolyn Beebe Smith, senior investigator at the U.S. National Institute of Mental Health.

“We do have to be cautious,” she says. “We have to look carefully at those [conditions] on an individual basis.”

The work was published 12 January in Frontiers in Molecular Neuroscience. An independent study published in November reported that a drug similar to rapamycin doesn’t appear to improve most features of TSC in 32 children with that condition2.

Both studies suggest that the drug may not benefit all people with autism or related conditions says Mustafa Sahin, who led the TSC study.

Rapamycin works by inhibiting a pathway led by the mammalian target of rapamycin (mTOR). This pathway is overly active in TSC because the proteins mutated in the condition normally serve as its brakes.

Some studies suggest that the pathway’s activity is also elevated in fragile X mice. However, the new study casts doubt on its role in fragile X.

“In science, some things become a hot topic. And when you have a hammer, everything looks like a nail,” says Mark Bear, professor of neuroscience at the Massachusetts Institute of Technology in Cambridge. “I just feel like the mTOR involvement in fragile X has been overhyped.” Bear was not involved in the work but has tested other drugs for fragile X syndrome.

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