A UCLA Health study found a single dose of the drug rapamycin rapidly reversed autism-like symptoms in adult mice whose mothers experienced inflammation during pregnancy. The improvements in brain communication and behavior occurred within two hours, suggesting the drug altered brain function, not structure. While the effects were temporary and rapamycin is not a viable human treatment, the findings point to new therapeutic targets focused on the brain's functional circuitry.
Maternal inflammation effects
- ▪Previous research has linked mild maternal inflammation to autism-like behaviors, unusual brain growth, seizures, and heightened sensory sensitivity in offspring
- ▪In the study, offspring of mice exposed to a mild inflammatory stimulus during pregnancy developed persistent inflammation, mild brain overgrowth, and excessive mTOR pathway signaling
- ▪A UCLA Health study in mice found that inflammation during pregnancy can cause lasting autism-like changes in offspring
Rapamycin treatment results
- ▪The treatment also led to a decline in repetitive behaviors, sensory sensitivity, and excessive responses to sensory input in the mice
- ▪Following rapamycin treatment, the mice's neurons began firing more normally, their vulnerability to seizures decreased, and communication between brain regions improved
- ▪A single dose of the drug rapamycin improved brain communication and autism-like behaviors in affected adult mice within about two hours
Mechanism of rapid response
- ▪The rapid two-hour response to rapamycin suggests the drug changed brain function rather than repairing underlying physical brain structures
- ▪Rapamycin works in part by reducing activity in the mTOR pathway, a biological signaling system that has been linked to some autism-related conditions
- ▪Researchers concluded that rapamycin rapidly restored a healthier balance in neuronal excitability in the mice's brains
- ▪Gene analysis showed rapamycin reversed abnormal gene expression patterns related to autism and epilepsy, with the strongest effects in excitatory neurons
Clinical limitations
- ▪Researchers stressed that rapamycin is not a practical treatment for these symptoms in humans
- ▪The benefits of the single rapamycin dose were temporary, and the drug can be toxic with repeated use
- ▪The study was conducted in mice, and daily treatment became less effective after several weeks as the animals developed a tolerance to the drug
Future therapeutic targets
- ▪The results point to the brain's functional circuitry, not just its physical structure, as a target for future therapies
- ▪Potential future therapeutic targets include mTOR pathway activity, brain network organization, and balancing neuronal excitation
- ▪Researchers suggest new approaches could include sensory circuit neuromodulation
- ▪The study's findings suggest the adult brain may be more adaptable than previously assumed, even with existing structural changes from early development
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