In brain science, great promise but many pitfalls, experts say at Brown forum

In the last few decades, scientists have made huge strides in mapping the human brain, using high-tech tools such as fMRI to show not just which areas handle which functions, but also how depression, addiction and other disorders manifest themselves in the brain’s circuitry.
They’ve also learned a lot about the brain’s chemistry, about specific proteins associated with diseases such as Alzheimer’s and Parkinson’s, and about the underlying genetics.
And yet worldwide, millions of people are still struggling with neurodegenerative diseases, with serious psychiatric disorders, with crippling depression. There’s remarkably little help for autistic children, and stroke is still the leading cause of disability.
It’s a major motivator for Dr. Michael Ehlers, senior vice president and chief scientific officer for neuroscience at Pfizer Inc., but also quite frustrating.
“We have an ever-increasing understanding of the disease processes and mechanisms,” he said, “and a seemingly declining ability to do anything about it.”
Ehlers, a former Duke University researcher, was a panelist at “The Future of the Brain,” a symposium sponsored by Brown University’s Institute for Brain Science on Oct. 13 and 14 that brought together top U.S. researchers in brain science, neurology and neurotechnology.
The event explored a wide range
of topics, including, on the second day, two panels on how cutting-edge brain research might lead to new therapies.
Justin Fallon, a Brown neuroscientist who is working to develop a treatment for muscular dystrophy, started the first discussion by noting how extraordinary this field is.
“The thing that makes the brain so incredibly inspiring and awesome is its complexity,” he said, “but that’s also what makes it so challenging.”
For a long time, he added, “we were really in the dark” about crucial aspects of brain function and their clinical implications. Yet the field has made huge strides, thanks to “an extraordinary convergence of understanding basic neurobiology, and using that understanding to support trials and translate that into therapeutics for the brain.”
Dr. Christopher Walsh, of Harvard Medical School and Boston Children’s Hospital, is mapping genetic mutations linked to neurological diseases. Ehlers, whose job is to turn scientific discoveries into actual drugs, cited several examples of insights that could lead to therapies for mood disorders, degenerative diseases, and more. Yet sometimes, he noted, promising ideas fail.
A second panel, moderated by Dr. Leigh Hochberg, a neurologist at Brown, Massachusetts General Hospital and the Providence VA Medical Center who is developing devices for people with neurologic damage, explored the frontiers of neurotechnology.
Dr. Brian Litt, of the University of Pennsylvania, described cutting-edge work being done in his lab to visualize how and why seizures occur, noting that the most common diagnosis in the field of epilepsy is “cryptogenic” – or in plain English, “I don’t know.”
Dr. Mahlon deLong, an Emory University neurologist, talked about the promise of using deep-brain stimulation (DBS), in which a device is implanted in the brain to deliver electrical charges, as a treatment for psychiatric disorders.
DBS has shown good results, deLong said, but it requires meticulous after-care, and its success or failure are harder to gauge with mental disorders than with, say, tremors.
“The genie is out of the bottle,” he said – there are two major industry-sponsored trials of DBS under way – but “we have to resist the pressures to proceed rapidly, and do this right.”
Yet Dr. Jaimie Henderson, of Stanford University, said the real question with DBS and other neurotechnologies is, “Are we moving too slow?”
Most innovations in the field are still beyond patients’ reach, he noted, and federal requirements for approval of new therapies are becoming more stringent, leading to longer delays. The new technologies are also expensive, beyond most people’s reach.
But compared with drugmakers, Ehlers argued, device-makers have it easy, because regulators are willing to accept greater risks with devices. “If you took any of these therapies and turned it into a pill,” he said, “it would have zero percent chance of approval.”
None of the neurotechnology researchers disagreed, but all noted that devices are geared to a very narrow audience: people for whom drugs don’t work.
“They’re miserable,” said deLong. “They think, this is the only hope. This is the last resort.” •