Just 10 years ago one of the dogmas of 20th century neuroscience – that adult humans do not make new brain cells – was overthrown. The discovery at the Salk Institute in California of adult neurogenesis, the creation of neurons, gave new hope to those seeking treatments for brain disease and inspired a great wave of neural research.
Leading investigators of neurogenesis discussed their findings at the BIO conference in Atlanta today, in the most fascinating scientific session I have attended here. The focus was on depression, which affects an estimated 15m Americans and hundreds of millions of people worldwide. As Saundra Maass-Robinson, an Atlanta psychiatrist, reminded us, fewer than half the patients treated with the antidepressant drugs available today “achieve remission” – in other words have their depression lifted.
Depression is a focus for neurogenesis research because neuroscientists, led by René Hen of Columbia University, discovered around 2003 that all antidepressant drugs achieve at least some of their effects by stimulating the growth of neurons in a region of the brain called the hippocampus, which is involved in learning and memory.
The conventional explanation for how antidepressants such as Prozac work is that they increase the production of certain neurotransmitters – brain chemicals such as serotonin that carry signals between neurons. But scientists have long been aware of a paradox here: the drugs change neurotransmitter levels very quickly but their clinical benefits only appear after a few weeks.
Hen’s hypothesis, that the delay in antidepressant action reflects the time taken for new cells to generate in hippocampus, has been confirmed by animal studies, brain imaging and postmortem examination of human brains – and is now widely accepted by neuroscientists.
The research led to the formation of BrainCells Inc (BCI), a biotech company in San Diego dedicated to developing new drugs for depression based solely on stimulating neurogenesis rather than neurotransmitters. Two candidate drugs, discovered by screening hundreds of chemicals to find ones that best trigger the proliferation of new cells in laboratory cultures of neurons, are already in early clinical trials and results will be available later this year, says BCI chief scientist Carrolee Barlow.
Of course if neurogenesis can be stimulated without unacceptable side-effects, there could be many other applications beyond depression. For example NeuroNova, a Swedish neurogenesis company targeting Parkinson’s disease and ALS, will be presenting its work here tomorrow.
To go from a basic biological discovery to clinical trials within a decade is remarkable. As Barlow says, “this is one of the fastest moving fields I have ever seen in science.”