Gene therapy breakthrough enables deaf boy to hear for the first time

[bnew]

Gene therapy breakthrough enables deaf boy to hear for the first time

The outcome of the treatment exceeded all expectations

www.theweek.in

Gene therapy breakthrough enables deaf boy to hear for the first time​

The outcome of the treatment exceeded all expectations

Web Desk Updated: January 24, 2024 11:19 IST

Aissam Dam, 11-year-old patient who received the gene therapy treatment (third from left) | Handout photo provided by Childrens Hospital of Philadelphia


In a remarkable breakthrough, an 11-year-old boy has regained his ability to hear after receiving pioneering gene therapy. Aissam Dam, from Morocco, who was born with congenital deafness, became the first person in the United States to undergo this revolutionary treatment. Thanks to the successful procedure, Dam can now experience the sounds of his father's voice and passing cars, marking a significant milestone in the field of gene therapy.

The cutting-edge treatment targeted a specific form of congenital deafness and is set to be trialed in younger children in the near future. Dam, who grew up in a world of complete silence, had never heard anything until his family relocated to Spain. It was there that they sought the help of a hearing specialist, who suggested that Dam might be eligible for a clinical trial involving gene therapy.

On October 4, 2023, Dam underwent a groundbreaking surgical procedure at the renowned Children's Hospital of Philadelphia (CHOP). The operation involved partially lifting his eardrum and introducing a modified virus, specifically engineered to transport functional copies of the otoferlin gene, into the fluid of his cochlea. This innovative approach kickstarted the production of the missing protein in his hair cells, ultimately restoring their proper function.

The outcome of the treatment exceeded all expectations, granting Dam access to a world of sound that was once entirely foreign to him. The success of this gene therapy procedure brings hope not only to patients around the globe suffering from hearing loss caused by genetic mutations but also to the wider medical community.

Despite the incredible achievement, reports suggest that Dam may face challenges in acquiring spoken language. The brain's window for acquiring speech typically closes around the age of five, making it unlikely for Dam to develop this skill. The US Food and Drug Administration, which granted approval for this groundbreaking study, prioritized older children for safety reasons, aiming to assess the efficacy and safety of the treatment before moving on to younger patients.

Gene therapy, a technique that modifies an individual's genes to treat or cure diseases, has emerged as a game-changing medical tool. It offers several mechanisms for therapeutic intervention, including the replacement of disease-causing genes with healthy copies or the inactivation of malfunctioning genes. This powerful approach has the potential to revolutionize the treatment landscape, providing new avenues of hope for individuals affected by genetic disorders.

 

[Orbital-Fetus]

Amazing.

 

[Morethan1]

I love it

 

[bnew]

Experimental gene therapy allows kids with inherited deafness to hear

Gene therapy has allowed several children born with inherited deafness to hear. A small study published Wednesday documents significantly restored hearing in five of six kids treated in China.

apnews.com

Experimental gene therapy allows kids with inherited deafness to hear​

1 of 3 | In this photo provided by researchers in January 2024, Dr. Yilai Shu examines a young patient at the Eye & ENT Hospital of Fudan University in Shanghai, China, after a gene therapy procedure for hereditary deafness. A small study published Wednesday, Jan. 25, 2024, in the journal Lancet, documents significantly restored hearing in five of six kids treated in China. (Courtesy Dr. Yilai Shu via AP)

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2 of 3 | In this image from video provided by the Children’s Hospital of Philadelphia, an 11-year-old boy who was born with hereditary deafness prepares for a gene therapy procedure in Philadelphia in October 2023. On Tuesday, Jan. 23, 2024, the hospital announced his hearing has improved enough that he now has only mild to moderate hearing loss in the ear that was treated, and is hearing sound for the first time in his life. (Children’s Hospital of Philadelphia via AP)

3 of 3 | In this image from video provided by the Children’s Hospital of Philadelphia, an 11-year-old boy who was born with hereditary deafness is given a hearing test in Philadelphia, after he underwent a gene therapy procedure in October 2023. On Tuesday, Jan. 23, 2024, the hospital announced his hearing has improved enough that he now has only mild to moderate hearing loss in the ear that was treated, and is hearing sound for the first time in his life. (Children’s Hospital of Philadelphia via AP)




BY LAURA UNGAR

Updated 6:31 PM EST, January 24, 2024

Gene therapy has allowed several children born with inherited deafness to hear.

A small study published Wednesday documents significantly restored hearing in five of six kids treated in China. On Tuesday, the Children’s Hospital of Philadelphia announced similar improvements in an 11-year-old boy treated there. And earlier this month, Chinese researchers published a study showing much the same in two other children.

So far, the experimental therapies target only one rare condition. But scientists say similar treatments could someday help many more kids with other types of deafness caused by genes. Globally, 34 million children have deafness or hearing loss, and genes are responsible for up to 60%of cases. Hereditary deafness is the latest condition scientists are targeting with gene therapy, which is already approved to treat illnesses such as sickle cell disease and severe hemophilia.

Children with hereditary deafness often get a device called a cochlear implant that helps them hear sound.

OTHER NEWS

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“No treatment could reverse hearing loss … That’s why we were always trying to develop a therapy,” said Zheng-Yi Chen of Boston’s Mass Eye and Ear, a senior author of the study published Wednesday in the journal Lancet. “We couldn’t be more happy or excited about the results.”

The team captured patients’ progress in videos. One shows a baby, who previously couldn’t hear at all, looking back in response to a doctor’s words six weeks after treatment. Another shows a little girl 13 weeks after treatment repeating father, mother, grandmother, sister and “I love you.”

All the children in the experiments have a condition that accounts for 2% to 8% of inherited deafness. It’s caused by mutations in a gene responsible for an inner ear protein called otoferlin, which helps hair cells transmit sound to the brain. The one-time therapy delivers a functional copy of that gene to the inner ear during a surgical procedure. Most of the kids were treated in one ear, although one child in the two-person study was treated in both ears.

The study with six children took place at Fudan University in Shanghai, co-led by Dr. Yilai Shu, who trained in Chen’s lab, which collaborated on the research. Funders include Chinese science organizations and biotech company Shanghai Refreshgene Therapeutics.

Researchers observed the children for about six months. They don’t know why the treatment didn’t work in one of them. But the five others, who previously had complete deafness, can now hear a regular conversation and talk with others. Chen estimates they now hear at a level around 60% to 70% of normal. The therapy caused no major side effects.

Preliminary results from other research have been just as positive. New York’s Regeneron Pharmaceuticals announced in October that a child under 2 in a study they sponsored with Decibel Therapeutics showed improvements six weeks after gene therapy. The Philadelphia hospital — one of several sites in a test sponsored by a subsidiary of Eli Lilly called Akouos — reported that their patient, Aissam Dam of Spain, heard sounds for the first time after being treated in October. Though they are muffled like he’s wearing foam earplugs, he’s now able to hear his father’s voice and cars on the road, said Dr. John Germiller, who led the research in Philadelphia.

“It was a dramatic improvement,” Germiller said. “His hearing is improved from a state of complete and profound deafness with no sound at all to the level of mild to moderate hearing loss, which you can say is a mild disability. And that’s very exciting for us and for everyone. ”

Columbia University’s Dr. Lawrence Lustig, who is involved in the Regeneron trial, said although the children in these studies don’t wind up with perfect hearing, “even a moderate hearing loss recovery in these kids is pretty astounding.”

Still, he added, many questions remain, such as how long the therapies will last and whether hearing will continue to improve in the kids.

Also, some people consider gene therapy for deafness ethically problematic. Teresa Blankmeyer Burke, a deaf philosophy professor and bioethicist at Gallaudet University, said in an email that there’s no consensus about the need for gene therapy targeting deafness. She also pointed out that deafness doesn’t cause severe or deadly illness like, for example, sickle cell disease. She said it’s important to engage with deaf community members about prioritization of gene therapy, “particularly as this is perceived by many as potentially an existential threat to the flourishing of signing Deaf communities.”

Meanwhile, researchers said their work is moving forward.

“This is real proof showing gene therapy is working,” Chen said. “It opens up the whole field.”___
The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.

 

[bnew]

Gene-therapy breakthrough allows congenitally deaf children to hear — Harvard Gazette

Harvard scientist co-leads research, which targeted specific condition, may yield other treatments for more of the 30 million kids with genetic hearing loss.

news.harvard.edu

Zheng-Yi Chen of Massachusetts Eye and Ear Infirmary and Harvard Medical School co-led the team that developed the gene therapy.
HEALTH

Gene-therapy breakthrough allows congenitally deaf children to hear​

Harvard scientist co-leads research, which targeted specific condition, may yield other treatments for more of the 30 million kids with genetic hearing loss

Alvin Powell
Harvard Staff Writer

January 24, 2024 6 min read

A novel gene therapy approach has given five children who were born deaf the ability to hear. The method, which overcomes a roadblock presented by large genes, may be useful in other treatments, according to researchers.

The work, conducted in Fudan, China, by a team co-led by Zheng-Yi Chen at the Massachusetts Eye and Ear Infirmary and Harvard Medical School and by collaborators at Fudan University’s Eye & ENT Hospital, treated six children aged 1 to 7 who were suffering from an inherited mutation of the OTOF gene, which manufactures a protein important in transmitting signals from the ear to the brain.

Five of the six children showed improvement in hearing over the 26-week trial, with four outcomes described by researchers as “robust.” With hearing a critical factor in language acquisition, researchers also measured speech perception — the ability to recognize sound as speech — and all five of those who responded to treatment showed improvement there.

The three older children, with cochlear implants turned off, could understand and respond to speech by 26 weeks, with two able to recognize speech in a noisy room and have a telephone conversation.

“This really opens the door to developing other treatments for different kinds of genetic deafness,” said Chen, a researcher at Mass Eye and Ear’s Eaton-Peabody Laboratories and a professor of otolaryngology, head and neck surgery at Harvard Medical School. Chen added that the study provides proof-of-concept that prior work in laboratory animals does translate to humans. “Now we can move forward in humans quickly. This has given us a real boost of confidence.”

Hearing loss affects more than 1.5 billion people worldwide, Chen said, including about 30 million cases of genetic impairment in children. Those in the current trial suffered a condition called DFNB9, resulting in total deafness due to a mutation in the OTOF gene.

The gene encodes the otoferlin protein, produced by cells in a snail-shaped part of the inner ear called the cochlea. In the cochlea, sound waves are translated into electric pulses carried by nerve cells to the brain, where they are interpreted as sound. Otoferlin plays a role in transmitting pulses from cochlear cells to the nerves and without it, sound is translated into electric signals but never reach the brain.

Chen, senior author of a paper on the work published this week in the journal The Lancet, and Yilai Shu, another senior author and deputy director of the Fudan hospital where the work took place, said DFNB9 provided an attractive gene-therapy target because it is a relatively simple condition, caused by a single mutation and involving no physical damage to the cochlear cells.



Shu, a postdoc in Chen’s lab from 2010 to 2014, said the large response to the request for study participants reflects the need for improved treatment for congenital deafness for which, Chen pointed out, there are no approved drugs. Researchers ultimately screened 425 potential participants, enrolling just six.

Of the six, four had cochlear implants — which, with training, allow interpretation of speech and sound — in one ear while the two youngest participants, ages 1 and 2, had no implants. When the implants were switched off, all participants were completely deaf.

Before the trial began, researchers had to tackle a significant technical problem related to the size of the OTOF gene. The procedure called for the gene to be inserted into the cochlea using a type of virus researchers commonly use for this purpose.

The virus inserts the gene into the DNA of target cells, which then begin to manufacture the missing protein. The problem in this case is that the OTOF gene is too big for the virus to hold. Researchers got past this by dividing the gene into two, encapsulating the halves into separate viruses, and then injecting a mixture with both halves of the gene into the cochlea.

Though the viruses inserted the gene halves at different spots on the cells’ DNA, when those halves were expressed, cellular machinery assembled the complete protein, restoring the cells’ ability to transmit signals to the brain.

The mixture was injected into the fluid of the inner ear, and the viruses made their way to the target cells as they would if they were a naturally occurring infection. Researchers had to wait for four to six weeks after injection to see the first signs that hearing was being restored.

In five of the six participants, the improvement was progressive. The three older children, with cochlear implants turned off, could understand and respond to speech by 26 weeks, with two able to recognize speech in a noisy room and have a telephone conversation.

The younger participants showed improvement in the ability to recognize speech but were too young for some tests. Anecdotally, Chen said the 1-year-old has been able to respond to stimuli and begun to verbalize simple first words, like “mama.” One of the six participants showed no improvement, which Chen and Shu said is poorly understood but may have been due to an immune reaction to the viral vector.

In some cases, Shu said, parents noticed the response even before the researchers conducted their first tests at four weeks.

“We first found out when the parents told us: When her mother called her, she turned back,” Shu said. “All of them are very hopeful. They were very, very excited, and all of them cried when they first found that their child can hear.”

The project, done in December 2022, was the first to make use of gene therapy to treat this condition, but several studies in various stages are targeting the same condition. Chen said that will hopefully accelerate work that, though it has taken years to reach this point, has recently seen rapid progress.

The study was funded by the National Natural Science Foundation of China, the National Key R&D Program of China, Science and Technology Commission of Shanghai Municipality, and Shanghai Refreshgene Therapeutics.

Next steps, he and Shu said, include monitoring the participants in this study, as well as beginning a new study with participants from more diverse backgrounds. If all goes well, Chen said, approval of the treatment by U.S. federal regulators could be three to five years away.

“This is truly remarkable. When we tell the story, even for our colleagues, it brings a tear to the eye,” Chen said. “I’ve been working in this field for three decades, and I know how difficult it has been to come to this point. I also know we’re at the juncture of a great future.”

 

[Rarely-Wrong Liggins]

A good deed done in a weary world.

 

[StoneColdSteveAustin]

and now hes gotta suffer through ice spice

 

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