Just as a mouse embryo takes only three weeks to develop, compared to a human’s nine months, the mouse embryonic stem cells take eighteen to twenty days to become hair cells. The human cells take forty. They require constant monitoring and tending, Heller said. “You can’t just close the incubator and come back in a week and hope for the best. You have to—every day—replace the culture medium. You have to look at the cells. You have to clean out areas you don’t like. It’s a little bit like a garden. You’re nurturing a very precious plant.” The iPS cells have to reproduce for about thirty generations before they can be used for experiments, which means it takes about 150 days to successfully culture-these cells from patients. By the spring of 2012 they had cultured biopsies from three genetically hearing-impaired patients. They had funding for about twelve altogether, from the NIH.
It’s a long way from mouse to man, but Heller said at the Hearing Restoration symposium that despite the challenge, “we’re getting close.”
One of the major findings of the last five or ten years, Heller said, is coming to understand the roadblocks. Once they know what obstacles stand in the way of transplantation, they can begin to figure out how to get around them. The first roadblock is the fact that these cells cause tumors. Looking ahead, Heller said, scientists need another five to ten years to solve that problem—a knotty one that involves learning how to generate pure cells and cells that are not tumorigenic. Once they solve that one, they will encounter new roadblocks: how to deliver the stem cells into the ear, determining the appropriate site for integration of cells, how to ensure their long-term survival, how to block immune system responses, how to make sure the cells function—“and, of course, whether the cells improve hearing.”
As a young assistant professor, Heller told the Hearing Restoration symposium, if he had been asked how long it would take to cure hearing loss, he would have said, “You know, in five years we’ll have a solution for certain things.” Over time, he went on, “I got a sense of the difficulty of the problem and of all the roadblocks and the issues we have to deal with. And I’m getting frustrated myself, how long it takes to overcome a single one of these roadblocks. And then you’re over one hill and there’s another one.” The difference now, he said, is that “we know where we have to go, and what we have to do. It’s difficult to assess whether it will take ten years or twenty years or even fifty years.”
Later, he went back to the time line again. “I think for transplantation we need another five to ten years before we are at the point where we can generate pure cells and cells that are not tumorigenic, to start doing experiments with animals.”
Ed Rubel, in our interview, also gave a time line for his lab’s work: “I think with proper funding, we can, in ten years, develop ways to get sufficient numbers of hair cells in a laboratory mammal cochlea as a model. We [meaning researchers in the field] will then go on to optimize the drug or drugs in all the ways needed to use them safely in humans, and only then go to clinical trials.” He pointed out that they already know some genes and some compounds that facilitate the production of new hair cells in some conditions, but they don’t have the lead compound. Even once they find that lead compound, he added, “all the safety trials, in vitro trials and small animal trials, all that preclinical work, usually takes eight to ten years.”
As for gene therapy, for those whose hearing loss has a genetic basis, Stefan Heller cites what happened with research on vision and blindness: “Twenty years ago this was an open field, and now it has evolved into a flourishing clinical field and a very lively biotechnology field” with a market for drugs and procedures. “I think we can use the vectors and tools they’ve developed and bring them into our field. So I think five to seven years is probably a reasonable time frame for seeing results in animal studies. Gene therapy would be used on people whose deafness is caused by a mutation in a certain gene. If you could deliver the correct gene into the inner ear, you might be able to repair hearing loss before it progresses too far for repair.
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Add CommentHearing loss due to loud noise has been shown , iron released during the loud noise.
Reply | Report Abuse | Link to this"Attenuation of cochlear damage from noise trauma by an iron chelator"
Coincidentally , siderosis also causes hearing loss.
"Superficial siderosis: A potentially important cause of genetic as well as non-genetic deafness"
The same method being used to treat aminoglycoside induced hearing loss ?
"The attenuation of gentamicin-induced hearing loss by iron chelators"
Will iron reduction attenuate deafness?