Matt Kaeberlein: Down Syndrome and Rapamycin

According to Kaeberlein: “Down Syndrome appears to be in many ways a condition of accelerated biological aging. One implication of this is that therapies that target biological aging, such as rapamycin, may be particularly beneficial for individuals with Down Syndrome.”

Individuals with Down Syndrome are at increased risk of developing Alzheimer’s disease-like dementia, which is characterized by the buildup of abnormal proteins in the brain called senile plaques and neurofibrillary tangles. Recent research has shown that the PI3K/AKT/mTOR pathway in the brain is disrupted in people with DS and this may contribute to age-related cognitive decline. The mTOR pathway is involved in regulating several important neuronal processes, including insulin signaling and autophagy, which are also disrupted in Alzheimer’s disease. In order to address this problem, researchers have developed a new treatment using mTOR inhibitors, which may prevent or reduce neurodegenerative symptoms by restoring normal mTOR signaling. To achieve this, they have developed a novel intranasal administration protocol of the drug rapamycin, which maximizes brain delivery while minimizing systemic side effects.

This study examines the effects of trisomy of chromosome 21, which causes Down syndrome, on brain chemistry and the potential for rapamycin treatment to correct these effects in a mouse model of the disorder. The study found that trisomy leads to changes in brain metabolites, specifically those involved in the dopaminergic, serotonergic, and kynurenine pathways, that become worse with age.

Additionally, the study found that long-term treatment with rapamycin reduces the accumulation of toxic metabolites in aged mice.


Another important study on rapamycin. Thank you for posting these studies, I enjoy reading them and love learning from them.

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