A toddler who was born completely deaf due to a rare genetic condition can now hear unaided thanks to a pioneering gene therapy.

Opal Sandy, who is now an 18-month-old girl from the U.K., is the youngest child in the world to receive this type of gene therapy, which uses a harmless, modified virus to correct genetic mutations in the body's cells. In this case, the therapy replaced a mutant gene associated with deafness with a working copy of that gene, according to a statement released May 9 by Cambridge University Hospitals.

Very similar gene therapies are being tested in other trials and have shown early success in treating slightly older children with the same type of hearing loss as Opal.

Known as auditory neuropathy, this type of hearing loss arises when the ears can detect sound but can't relay that information to the brain. The condition is caused by mutations in a gene called OTOF that normally makes otoferlin, a protein needed for the inner ear to talk to neurons that are linked to the brain. The condition accounts for between 1% and 8% of cases of congenital hearing loss that occurs in the absence of other symptoms.

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Opal was diagnosed at 3 weeks old. When she was 11 months old she became the first patient treated in a global trial of the new gene therapy. She was given the new treatment via an injection into her right ear. The virus injected during the procedure known as an adeno-associated virus delivers a working copy of OTOF to cells in the ear to replace the mutated version. Afterwards, the virus is naturally eliminated from the body.

Doctors also installed a cochlear implant in Opal's left ear; these devices help users hear some sound by relaying signals to the brain that their ear cells can't.

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Within four weeks of the gene therapy, Opal could respond to sounds even when her cochlear implant was switched off, her doctors reported. Twenty-four weeks out from treatment, her treated ear could pick up soft sounds, such as whispering, at "close to normal" hearing levels. Now, at 18 months old, Sandy can respond to her parents' voices without her implant activated and say words such as "dada" and "bye-bye."

"When Opal could first hear us clapping unaided it was mind-blowing we were so happy when the clinical team confirmed at 24 weeks that her hearing was also picking up softer sounds and speech," Opal's mother Jo said in the statement. Her father, James, noted that Opal can't wear her implant in certain contexts, such as in the bath, so the therapy is already making a difference in their day-to-day lives.

The ongoing trial that Opal is part of is enrolling patients in the U.S., the U.K. and Spain. In this stage of the research, patients receive a low dose of the therapy in one ear. Future trials will test the therapy at higher doses in one ear and then in both ears. Patients will be followed up for five years to assess long-term outcomes.

"Gene therapy has been the future of otology and audiology for many years and I'm so excited that it is now finally here," Dr. Manohar Bance, chief investigator of the trial and a professor of otology and skull base surgery at the University of Cambridge in the U.K., said in the statement.

"This is hopefully the start of a new era for gene therapies for the inner ear and many types of hearing loss," he said.

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Deaf baby can hear after 'mind-blowing' gene therapy treatment - Livescience.com

Disc-related back pain may one day meet its therapeutic match: gene therapy delivered by naturally derived nanocarriers that, a new study shows, repairs damaged discs in the spine and lowers pain symptoms in mice.

Scientists engineered nanocarriers using mouse connective-tissue cells called fibroblasts as a model of skin cells and loaded them with genetic material for a protein key to tissue development. The team injected a solution containing the carriers into damaged discs in mice at the same time the back injury occurred.

Assessing outcomes over 12 weeks, researchers found through imaging, tissue analysis, and mechanical and behavioral tests that the gene therapy restored structural integrity and function to degenerated discs and reduced signs of back pain in the animals.

We have this unique strategy thats able to both regenerate tissue and inhibit some symptoms of pain, said co-senior author Devina Purmessur Walter, associate professor of biomedical engineering at The Ohio State University.

Though there is more to learn, the findings suggest gene therapy could offer an effective and long-lasting alternative to opioids for the management of debilitating back pain.

This can be used at the same time as surgery to actually boost healing of the disc itself, said co-senior author Natalia Higuita-Castro, associate professor of biomedical engineering and neurological surgery at Ohio State. Your own cells are actually doing the work and going back to a healthy state.

The study was published online recently in the journal Biomaterials.

An estimated 40% of low-back pain cases are attributed to degeneration of the cushiony intervertebral discs that absorb shocks and provide flexibility to the spine, previous research suggests. And while trimming away bulging tissue from a herniated disc during surgery typically reduces pain, it does not repair the disc itself which continues to degenerate with the passage of time.

Once you take a piece away, the tissue decompresses like a flat tire, Purmessur Walter said. The disease process continues, and impacts the other discs on either side because youre losing that pressure that is critical for spinal function. Clinicians dont have a good way of addressing that.

This new study builds upon previous work in Higuita-Castros lab, which reported a year ago that nanocarriers called extracellular vesicles loaded with anti-inflammatory cargo curbed tissue injury in damaged mouse lungs. The engineered carriers are replicas of the natural extracellular vesicles that circulate in humans bloodstream and biological fluids, carrying messages between cells.

To create the vesicles, scientists apply an electrical charge to a donor cell to transiently open holes in its membrane, and deliver externally obtained DNA inside that converts to a specific protein, as well as molecules that prompt the manufacture of even more of a functional protein.

In this study, the cargo consisted of material to produce a pioneer transcription factor protein called FOXF1, which is important in the development and growth of tissues.

Our concept is recapitulating development: FOXF1 is expressed during development and in healthy tissue, but it decreases with age, Purmessur Walter said. Were basically trying to trick the cells and give them a boost back to their developmental state when theyre growing and at their healthiest.

In experiments, mice with injured discs treated with FOXF1 nanocarriers were compared to injured mice given saline or mock nanocarriers and uninjured mice.

Compared to controls, the discs in mice receiving gene therapy showed a host of improvements: The tissue plumped back up and became more stable through production of a protein that holds water and other matrix proteins, all helping promote range of motion, load bearing and flexibility in the spine. Behavioral tests showed the therapy decreased symptoms of pain in mice, though these responses differed by sex males and females showed varying levels of susceptibility to pain based on the types of movement being assessed.

The findings speak to the value of using universal adult donor cells to create these extracellular vesicle therapies, the researchers said, because they dont carry the risk of generating an immune response. The gene therapy also, ideally, would function as a one-time treatment a therapeutic gift that keeps on giving.

The idea of cell reprogramming is that you express this transcription factor and the cell is then going to convert to this healthier state and stays committed to that healthier phenotype and that conversion is not normally transient, Higuita-Castro said. So in theory, you would not expect to have to re-dose significantly.

There are more experiments to come, testing the effects of other transcription factors that contribute to intervertebral disc development. And because this first study used young adult mice, the team also plans to test the therapys effects in older animals that model age-related degeneration and, eventually, in clinical trials for larger animals known to develop back problems.

Higuita-Castro, director of advanced therapeutics and engineering in the College of MedicineDavis Heart and Lung Research Institute and a core faculty member of Ohio StatesGene Therapy Institute, and Purmessur Walter, an investigator in Ohio States Spine Research Institute and director of the Spinal Therapeutics Laboratory in the College of Engineering, are co-principal investigators on National Institutes of Health grants funding this research.

Additional co-authors include co-first authors Shirley Tang and Ana Salazar-Puerta, Mary Heimann, Kyle Kuchynsky, Mara Rincon-Benavides, Mia Kordowski, Gilian Gunsch, Lucy Bodine, Khady Diop, Connor Gantt, Safdar Khan, Anna Bratasz, Olga Kokiko-Cochran, Julie Fitzgerald and Benjamin Walter, all of Ohio State; Damien Laudier of Icahn School of Medicine at Mount Sinai; and Judith Hoyland of the University of Manchester.

Ohio State has filed a patent application on nonviral gene therapy for minimally invasively treating painful musculoskeletal disorders.

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Gene therapy relieves back pain, repairs damaged disc in mice - The Ohio State University News