Researchers at Harvard Medical School and Boston Children's Hospital have found a potential treatment for hereditary deafness, the same condition thought to have caused Ludwig van Beethoven to lose his hearing.
The scientists are using a new gene-editing approach that they say could someday prevent profound hearing loss.
Beethoven's Symphony No. 5 is a cornerstone of classical music. It is hard to believe the composer was almost completely deaf from a genetic condition when he finished it.
"These children are born fairly normal, but then over 10 or 20 years, they lose their hearing," Harvard neurobiology professor Dr. David Corey.
Aptly named "Beethoven mice" might hold the key to a potential cure. Scientists believe the animals have a defect in the same gene that may have caused Beethoven's deafness.
"Our genome is composed of about 3 billion letters of DNA that together make up 20,000 genes," Corey explained. "For the disease we're studying, one mistake in the DNA in one of the genes causes deafness."
Researchers identified that hearing gene called TMC1. It's a gene that comes in pairs.
Using a newly refined gene-editing system, they disabled the defective copy of the TMC1 gene, leaving the good gene in place.
"By eliminating just the bad copy, that would be sufficient to preserve hearing," Corey said.
The scientists then delivered the edited DNA back into the cells of the mice and tested their hearing.
"We put little scalp electrodes on the back of the head, play sounds into the ear and can measure the brain activity in response," Boston Children's Hospital professor of otolaryngology Dr. Jeffrey Holt said.
Researchers say the mice were able to hear sounds as low as 45 decibels, the level of a quiet conversation.
"This could be life-changing," Holt said.
A famed composer, his namesake mice and a team of scientists are using cutting-edge medicine to help people who would otherwise go deaf.
The scientists say this research paves the way for using the new editing system to treat as many as 3,500 other genetic diseases that are caused by one defective copy of a gene.
It's important to note that Holt holds patents on TMC1 gene therapy.
MEDICAL BREAKTHROUGHSRESEARCH SUMMARYTOPIC: BEETHOVEN MICE PREVENT DEAFNESS: MEDICINE'S NEXT BIG THING?REPORT: MB #4689
BACKGROUND: In the United States, hearing loss affects 48 million people and can occur at birth or develop at any age. One out of three people over the age 65 have some degree of hearing loss, and two out of three people over the age 75 have a hearing loss. Children in the United States are estimated at 3 million in having a hearing loss, and of those, 1.3 million are under the age of three. One of the leading causes of hearing loss is noise, and while preventable, can be permanent. Listening to a noisy subway for just 15 minutes a day over time can cause permanent damage to one's hearing. Listening to music on a smartphone at high volumes over time can cause permanent damage to one's hearing as well. The number of people with hearing loss is more than those living with Parkinson's, epilepsy, Alzheimer's, and diabetes combined. (Source: https://chchearing.org/facts-about-hearing-loss/ and https://hearinghealthfoundation.org/hearing-loss-tinnitus-statistics/)
TREATMENTS: The treatment you receive will depend on the cause and severity of the hearing loss. A reversible cause of hearing loss is earwax blockage where your doctor may remove earwax using suction or a small tool with a loop on the end. Some types of hearing loss can be treated with surgery, including abnormalities of the ear drum or bones of hearing (ossicles). Repeated infections with persistent fluid may result in your doctor inserting small tubes to help your ears drain. If your hearing loss is due to damage to your inner ear, a hearing aid can be helpful. With more severe hearing loss and limited benefit from conventional hearing aids, a cochlear implant may be an option. Unlike a hearing aid that amplifies sound and directs it into your ear canal, a cochlear implant bypasses damaged or nonworking parts of your inner ear and directly stimulates the hearing nerve. (Source: https://www.mayoclinic.org/diseases-conditions/hearing-loss/diagnosis-treatment/drc-20373077)
GENE EDITING WITH CRISPR: Scientists at Harvard Medical School and Boston Children's Hospital have used a newly tailored gene-editing approach in mice thought to have the same genetic defect that caused famed composer Beethoven to go deaf in adulthood. CRISPR-Cas9 gene editing works by using a molecule to identify the mutant DNA sequence. Once the system pinpoints the mutated DNA, the cutting enzyme, or Cas9, "snips" it; however, the gene editors are not always accurate. Sometimes, the guide RNA that leads the enzyme to the target site and the Cas9 enzyme are not precise and could cut the wrong DNA. The Harvard and Boston Children's scientists are using a modified Cas9 enzyme derived from Staphylococcus aureus bacteria that they are finding is significantly more accurate. (Source: https://hms.harvard.edu/news/saving-beethoven)
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