An end to deafness? New professor's research looks to ear drops, stem cells

Steve Gladfelter/VAS

Stefan Heller, whose reflection can be seen in the droplet, will be testing some 100,000 drugs over the next decade in his new lab to see if any will yield an ear drop that alleviates hearing loss.

His dream is to someday use ear drops to cure deafness. On a recent morning, Stefan Heller, PhD, explained this by tilting his head to the side and squeezing imaginary drops into his right ear.

Heller's eyes light up. The cure could be that simple.

As a leader in stem cell-based research on the inner ear, Heller, newly arrived at the School of Medicine direct from the Harvard faculty, has a step-by-step plan for making this dream come true. It will, at the very least, take another decade or so, but if anyone can do it, he's the guy to place your bets on.

"Heller's a world-class scientist and originator in this field," said Robert Jackler, MD, the chair of the otolaryngology department who helped recruit Heller to spearhead research into possible cures for deafness. "He came here to assemble a team around his vision."

Heller's vision is to work together with the many experts on the Stanford campus to come up with a variety of possible cures for deafness from drug therapy treatment—which could be as simple as an application of ear drops—to stem cell transplantation into the inner ear to remedy hearing loss.

"Everyone asks 'How long before we do this?'" said Heller, associate professor of otolaryngology, whose accent still bears the trace of his native Germany. "I tell them the devil is in the details."

But even at the national level, those in the research community remain hopeful that Heller's work will reap successes sooner rather than later.

James Battey, MD, director of the National Institute on Deafness and Other Communication Disorders, lauded Heller as "one of the leading auditory neuroscientists" and points to his stem cell regeneration research as a "high priority" for the institute. Dean Philip Pizzo, MD, described Heller's work as "enormously promising."

The goal, both Jackler and Heller agreed, is to see possible treatments within five to 10 years, though the early experimental approaches to therapy have to be tested extensively on laboratory animals first.

Heller gained international attention for having first identified stem cells that reside within the inner ear in 2002. Since then, his research has focused on using these stem cells to regenerate critically needed hair cells in the inner ear. It's these cells that convert the mechanical energy of sound into electrical impulses that are sent to the brain so that we can hear.

Humans are born with 15,000 hair cells per ear. When a significant number of these cells are lost or damaged, hearing loss occurs. Unlike in other species such as birds, humans are unable to spontaneously regenerate these hearing cells.

"There are no deaf birds," observed Heller. "This is hopeful because it means the genetic program for regeneration exists somewhere in the vertebrate family."

This explains why Heller has centered his research on stem cells as the key to unlocking future cures for hearing disorders. Following the identification of the stem cells in the ear, his research group reached another significant milestone: the team demonstrated in 2002 that it is possible to coax embryonic stem cells in a test tube to differentiate into hair cells—and then also to differentiate after transplantation in chicken embryos' ears.

"Embryonic stem cell-based approaches are probably the linchpin to finding a drug-based treatment for deafness," said Heller. He's been working on developing the necessary technology to go forward with his drug therapy research, which will entail screening about 100,000 drugs on progenitor hair cells that he has successfully grown in the lab, converted from embryonic stem cells. After pinpointing any drugs found to be promising candidates, clinical tests will follow, also to be conducted on the Stanford campus.

Heller's hope is to cure deaf mice using drug therapy within the next five to eight years and next move on to humans. At the same time, Heller has a grant from the McKnight Endowment Fund for Neuroscience to continue his research into stem cell transplantation.

While potential cures for deafness are, in fact, as variable as the many causes of hearing loss, Heller said, the simple use of ear drops to cure the most common causes of deafness, such as the natural aging process and exposure to loud noises, is currently his favorite plan.

"The ear is good for drug treatment," Heller said. "You can do local treatment without affecting the whole body."

This idea has been at the back of his mind since he began researching the inner ear 10 years ago, and it has become more plausible as a result of his lab's successes in the field of stem cell research over the past four years.

"Treatment may not be as broad as people think," Heller said. "It may help some people and not others." For some people with genetically caused hearing disorders, he explained, no drug is likely to help. "For them, stem cell transplantation may be the answer," he said.

But for the majority of those with hearing loss, particularly in the aging population, drug therapy could be the answer. As the population has aged and noise pollution has grown more severe, health experts now estimate that one in three adults over the age of 65 has developed a handicapping hearing loss.

An unassuming man of 40, Heller spent his first few weeks at Stanford after arriving in October dashing around campus in shorts, unpacking boxes, helping his wife (who is also his lab manager) set up shop, and helping his team of researchers, six who followed him here from Harvard, cope with the daunting Silicon Valley real estate market.

"Everyone's found housing," said Heller with a relieved sigh.

On weekdays the team works on cures for deafness. On weekends they play soccer together, including Heller's two bearded collies, Sepp and Kalle. "We're almost like a family," his wife and high school sweetheart Sabine Mann said of the research team.

Moving to Stanford wasn't an easy decision, because it meant uprooting so many people, Heller added. But the advantages of both California's support of stem cell research with the passage of Proposition 71, the state's $3 billion stem cell initiative, and what he calls the "collaborative" atmosphere on the Stanford campus ultimately won out.

"I am very much interested in basic research," Heller said. "But deafness is a clinical problem. I would like to connect basic science with potential clinical applications. I think this, now more than ever, is the future of medicine."