Surgeon Tries to Reach Behind the Eardrum to Treat Hearing Disorders
Anil K. Lalwani, a professor in the Department of Otolarayngology, picked a particularly challenging—and tiny—target to aim for when he joined the faculty of the Columbia University College of Physicians and Surgeons in 2012.
One of the leading ear surgeons in the country, he wanted to find a way to deliver medicine directly into the inner ear, the best way to treat disorders that include hearing loss, balance problems and numerous genetic conditions. To get it there, he’d have to reach a delicate membrane located directly behind the eardrum and embedded in a wall of bone hard enough to stop a bullet. The size of his target? About as small as the period at the end of this sentence.
It is a task requiring extraordinary precision. “You could cause deafness if you make holes too big, or if the holes are big enough that the fluid inside the inner ear could leak out—and if you pick too big of a needle it tears the membrane,” he said.
Lalwani is collaborating on this research with Jeff Kysar, chair of Columbia’s department of mechanical engineering. He has spent much of his career studying disorders of the cochlea, the fluid-filled, seashell-shaped structure (cochlea means “snail” in Latin) that plays a crucial role in hearing by translating sound waves into nerve impulses that are sent to the brain. Different sound waves at multiple frequencies oscillating all at once allow us to recognize a familiar voice, get swept away by a love song or flinch at a loud noise.
He hadn’t originally planned on a career in otolaryngology, the treatment of ear, nose and throat disorders. A native of India, he moved with his family to Michigan at age 10, attended the University of Michigan Medical School and interned in general and thoracic surgery at Duke. But he developed second thoughts about that specialty: The program was 10 years long and known to be incredibly demanding.
So Lalwani, who had just married, switched his specialty to otolaryngology, transferred to the University of California San Francisco (UCSF) and, upon graduating, joined the National Institute on Deafness and Other Communication Disorders in Bethesda, Maryland. While there, he collected DNA from two dozen members of an extended family susceptible to a progressive form of nonsyndromic hearing loss.
Taking the samples back to UCSF, he mapped and identified a mutation in the MYH9 gene in family members with the disease. The disorder was caused, he discovered, by the equivalent of a few typos in the two billion nucleotide genetic code that led to the malformation of microscopic cochlear hair cells. That was enough to result in complete deafness.
Lalwani began to experiment to see if the disease could be cured by rewriting the aberrant DNA. Gene therapies for other diseases are generally delivered by inserting the desired DNA into hollowed out viruses and then getting the virus to attach to a desired target and inject its cargo into the cell’s nucleus.
But getting the carriers of the new DNA into the inner ear proved particularly tricky. When he arrived at Columbia in 2012, he resolved to solve that problem.
Many people have tried injecting materials through the eardrum, hoping that some medicine would get through the membrane and into the inner ear. The method was unreliable because it was impossible to know how much would get through. The viruses used in gene therapy, meanwhile, had difficulty diffusing through the membrane because they are larger than most small molecular drugs.
Lalwani and Kysar believe that they have found methods that could overcome this problem. They learned that the membrane’s unusual shape—which Lalwani compares to that of a Pringles potato chip—gives it the tensile strength to withstand large pressure changes, but also makes it especially susceptible to tears from certain kinds of needles.
With support from a National Institutes of Health grant, the two researchers are studying this shape and designing tools to make either temporary or permanent holes, lift up the eardrum and insert a microneedle. They hope to develop a way to go straight through the eardrum, creating a temporary hole that would heal on its own. An additional benefit to this approach is that the hollow needle could suck out some inner ear fluid to be used for diagnostic purposes.
And that, says Lalwani, could open up a “whole area of precision medicine.”