At Novartis’s research lab in Cambridge, Massachusetts, a large incubator-like piece of equipment is helping give birth to a new era of psychiatric drug discovery. Inside it, bathed in soft light, lab plates hold living human stem cells; robotic arms systematically squirt nurturing compounds into the plates. Thanks to a series of techniques perfected over the last few years in labs around the world, such stem cells—capable of developing into specialized cell types—can now be created from skin cells. When stem cells derived from people with, say, autism or schizophrenia are grown inside the incubator, Novartis researchers can nudge them to develop into functioning brain cells by precisely varying the chemicals in the cell cultures.
They’re not exactly creating schizophrenic or autistic neurons, because the cells aren’t working within the circuitry of the brain, but for drug-discovery purposes it’s the next best thing. For the first time, researchers have a way to directly examine in molecular detail what’s going wrong in the brain cells of patients with these illnesses. And, critically for the pharmaceutical company, there is now a reliable method of screening for drugs that might help. Do the neurons look different from normal ones? Is there a flaw in the way they form connections? Could drugs possibly correct the abnormalities? The answer to each of these questions is a very preliminary yes.
The technique is so promising that Novartis has resumed trying to discover new psychiatric drugs after essentially abandoning the quest. What’s more, it’s been introduced at a time when knowledge about the genetics behind brain disorders is expanding rapidly and other new tools, including optogenetics and more precise genome editing (see “Neuroscience’s New Toolbox”), are enabling neuroscientists to probe the brain directly. All these developments offer renewed hope that science could finally deliver more effective treatments for the millions of people beset by devastating brain disorders.