Can brain disorders be treated more effectively by fine-tuning key receptors in the brain, rather than turning them completely on or off? That’s the question Boston-based Third Rock Ventures’ latest startup, Sage Therapeutics, hopes to answer with a new class of treatments it is developing to treat diseases such as schizophrenia and depression. Third Rock started Sage today with $35 million and a duo of co-founders who are well known in the neuroscience space: Eli Lilly veteran Steven Paul, who is now the director of the Helen and Robert Appel Alzheimer’s Disease Research Institute at Weill Cornell Medical College in New York, and Douglas Covey, professor of biochemistry at the Washington University School of Medicine in St. Louis.
Sage is developing “allosteric receptor modulators,” which are designed to balance the activity of neurons in the brain. The drugs address neurotransmitters such as GABA and glutamate, which control signals transmitted between neurons. When the receptors that produce these brain chemicals go awry—causing them to be either overly active or not active enough—disorders of the central nervous system can result.
The problem with many drugs on the market today, says Third Rock partner Kevin Starr, is they turn neurotransmitters all the way up or they turn them off all together. “That might not be the best way to restore the natural signaling in the brain,” he says. “You don’t want to hit these receptors over the head. You want to fine-tune them.”
Sage is founded on a proprietary chemistry-based technology that enables the development of novel allosteric receptor “modulators”—drugs designed to tweak their activity rather than just shutting them on or off.
Paul says one project the company is working on involves finding drugs that will boost the glutamate receptor called NMDA, which is believed to be underactive in the brains of patients with schizophrenia. “NMDA was a very active area of research when I was at Lilly,” says Paul (who is also one our New York Xconomists). But finding
