’Last year, scientists described neuropsychiatric drug development as “in the midst of a crisis” because of all the mouse findings that fail to translate to people. Of every 100 neuropsychiatric drugs tested in clinical trials — usually after they “work” in mice — only nine become approved medications, one of the lowest rates of all disease categories.
…In the most detailed taxonomy of the human brain to date, a team of researchers as large as a symphony orchestra sorted brain cells not by their shape and location, as scientists have done for decades, but by what genes they used. Among the key findings: Mouse and human neurons that have been considered to be the same based on such standard classification schemes can have large (tenfold or greater) differences in the expression of genes for such key brain components as neurotransmitter receptors.
That makes neurons and circuits connecting brain regions, which were long thought to be essentially identical in mice and people, different in a fundamental way. And it could explain the abysmal record of drug development for neuropsychiatric diseases including schizophrenia, depression, bipolar disorder, and autism.…’