Category Archives: Genetic Therapy

An 11-year-old deaf boy is now able to hear in one ear after undergoing a gene therapy treatment at Childrens Hospital of Philadelphia, one of the first such cases in the world. A second boy, aged 3, is scheduled to receive the treatment at CHOP on Friday.

Yet the news has drawn dismay from some who can best appreciate whats at stake: other deaf people.

For many deaf people, deafness is not something that needs to be fixed. Unlike other medical conditions that have been treated with gene therapy, deafness is not a disease and it doesnt deprive someone of a long, rich life. Similar concerns were raised years ago with the invention of cochlear implants, electronic devices that merely approximate the sense of hearing.

But physicians say gene therapy is likely to yield even better results, providing normal or near-normal hearing ability to thousands of people born with rare types of deafness. More than a decade after the first successful gene therapy was tested at CHOP, the technology has come of age, enabling doctors to treat conditions from blindness to hemophilia. The new treatment for deafness required still more innovation by the Philadelphia hospital: developing a delicate procedure to reach a precise location in the inner ear.

Sara Novi, a novelist who lives in Montgomery County, was among many deaf people objecting on social media that they never asked for the innovation. She thinks society would do better to spend more on sign-language education and other underfunded support services, rather than a cutting-edge therapy that is likely to cost more than $1 million per patient.

Human diversity should be cherished, not winnowed out for the convenience of the majority, she said by email. Is it ethically sound to experiment on a child for a non-lifesaving treatment from which the benefit is questionable, and who cannot legally consent?

The procedure on 11-year-old Aissam Dam was performed with the full consent of his hearing parents. His father brought him to Philadelphia from Spain for the treatment in October. Within weeks, he was able to hear sound for the first time, going from profoundly deaf in the treated ear to having a mild to moderate hearing loss.

Physicians say he is likely too old to learn to speak, a complex skill that requires the flexible, plastic brain of early childhood. Still, he can hear his parents voices, car engines, and other novelties. The 3-year-old scheduled for treatment on Friday, along with younger study participants to come later, is likely to do much better with spoken language.

From a technical standpoint, theres no question that the treatments represent a big step forward, requiring innovation both in science and surgery.

Participants in the studies were born with rare genetic mutations that prevented cells in their inner ears from making a type of protein needed for normal hearing. Yet their ears were otherwise intact, like a microphone that doesnt work simply because of a faulty connection, said CHOP surgeon John A. Germiller, who specializes in treating the ear, nose and throat.

The microphone is working. The wires working, he said. But theres a break in the electrical connection.

Thats why it made sense to try gene therapy, which involves replacing or altering mutated genes. For this type of deafness, it would require injecting participants such as Aissam with a normal, unmutated copy of the genetic recipe for that missing protein.

But this particular recipe (a gene called OTOF) was too big to load onto gene therapy vectors the inactivated viruses that are used to deliver the genetic instructions inside recipients cells. (Think of the instruction manual for an alarm clock vs. one for a computer.)

So scientists had to break the recipe in two. Half of it was loaded onto some of the viral vectors, the remaining half onto others. The two halves of the recipe could then be injected together into the persons ear cells, where they would reassemble into one complete set of instructions so the missing protein could be made.

The version administered at CHOP was manufactured by Akouos Inc., a subsidiary of Eli Lilly.

But the injection was no easy task. The therapy had to be delivered to tiny hair cells inside the cochlea, the snail-shaped apparatus located behind the eardrum.

Thats where Germiller came in. A decade earlier, he had pioneered a delicate technique to perform a different procedure inside the cochlea. Akouos officials asked the CHOP surgeon whether he could modify his method slightly to administer the gene therapy, and he said yes.

For the October procedure, Germiller used one hand to insert an endoscope into Aissams ear, enabling him to watch what he was doing on a big computer screen. In the other hand, the physician held a slender tool called an elevator, which he used to gently peel back one edge of the boys eardrum.

Next came a third tool, an ultra-thin needle with the end bent at a slight angle. He inserted it past the eardrum and through a tiny membrane on the outer wall of the cochlea, then depressed a small pump to inject two droplets of the therapeutic solution.

Germiller demonstrated recently in a training lab at CHOP, reenacting the steps on a child-sized mannequin while watching the computer screen above.

We see exactly where were going, he said.

Several weeks later, after swelling from the procedure subsided, audiologists piped a series of beeps into Aissams ear at a range of volumes, asking him to raise his hand to indicate whether he could hear. Germiller said the boys hearing ability varies from frequency to frequency, but it is roughly equivalent to that of a person with normal hearing who wears foam earplugs.

Speaking to the New York Times by sign-language interpreter, Aissam said he welcomed the novel sensations.

Theres no sound I dont like, he said.

Among the deaf people with concerns about the gene therapy is one who also happens to be a scientist.

Sara Blick-Nitko, a post-doctoral scholar at the University of Rochester School of Medicine and Dentistry, said gene therapy makes sense if it could help an older person who lost hearing as an adult. But for someone who is born deaf, the treatment smacks of eugenics, erasing a genetic trait without regard for its associated rich culture and language.

Being deaf is not a disease, she said. It truly enriches your life, when you have access to your native language and the resources to be successful.

With cochlear implants, the deaf communitys concern is not so much the devices themselves, but the way they are used. They are often implanted in deaf children who are born to hearing parents, many of whom mistakenly think that the devices provide normal or near-normal hearing. As a result, such children, who often struggle to learn to speak, also are less likely to be taught a full-fledged language that anyone can learn from infancy: sign language.

Germiller, the CHOP surgeon, is well aware of these concerns. But he says that for certain rare forms of deafness, gene therapy is likely to work even better than cochlear implants, potentially providing the recipient with normal, natural-sounding hearing.

William J. Parkes, an ear, nose, and throat specialist at Nemours Childrens Health who is not involved with any of the studies, agreed.

This is the next major breakthrough, he said.

Perhaps but only when it works, countered Jennifer Reesman, a Maryland-based neuropsychologist who counsels deaf and hard-of-hearing children and their families.

In another one of the gene therapy studies, a joint effort by researchers from Harvard and China, five deaf children gained the partial ability to hear after treatment, while a sixth did not.

Without knowing how well the therapy will work in any one case, it is essential that all deaf children learn sign language from infancy, when the brain is best at picking up languages, Reesman said. If their parents also want them to speak, thats great, too, just like raising a child to speak English and Spanish.

How do we ensure that were providing solid access to language so a child can be successful no matter what their outcome is regarding access to sound? she said.

For some in the deaf community, decisions to get gene therapy or cochlear implants are best left to the individual once they reach adulthood.

Yet therein lies a medical catch-22: The people who stand to gain the most from gene therapy are infants, so the decisions generally will be made by their parents. And because most parents of deaf children can hear, it can be hard for them to appreciate the value of the deaf community.

Novi, the Montgomery County novelist who is deaf, calls it a case where science has outpaced a discussion of the ethical nuances involved.

Doctors will argue that there is convenience to be gained, but I dont think easy always equals best, she said. Lots of marginalized folks experience barriers in our society, but that doesnt mean we should manipulate their genes to make it easier for them.

Read more from the original source:
CHOP treats deaf children with Eli Lilly gene therapy, but deaf community objects - The Philadelphia Inquirer