In a promising step against a genetic disease that causes deafness and gradual loss of vision, scientists have partly restored hearing with a single injection to young mice.
Experts praised the study on Usher syndrome, published online last week by the journal Nature Medicine, but the results are still a long way from preventing the disease.
Children with Usher—an estimated one in 6,000 to 7,500 babies worldwide—are born deaf. The visual component of the disease, called retinitis pigmentosa, often starts in childhood, but severe problems are more likely in adolescence and young adulthood. About half of adults with Usher can still read a newspaper into their 50s.
Some groups, such as Louisiana's Cajuns and Canada's Acadians, have an unusually high prevalence of the disease.
In the study, Michelle Hastings of Chicago Medical School and Jennifer Lentz of the Louisiana State University Health Science Center found that one injection allowed affected mice to hear for months.
The injection, or patch, is a laboratory-created fragment of RNA, which is a chemical cousin of DNA. The patch was designed to interfere with the effects of a faulty gene.
"It's a very promising and striking finding," said Dr. Henry Paulson, a University of Michigan specialist in neurodegenerative diseases.
"Curing a mouse is quite different from curing a human," he said, but he's cautiously optimistic.
Lentz, the study's lead author, and Hastings, senior author, have received a $1.3 million grant from the National Institutes of Health for four more years of mouse studies to learn the treatment's physical effects and to refine timing of shots.
Time erodes the effects of the gene-inhibiting patch over the faulty RNA, and researchers plan to test whether booster shots retain hearing in treated mice. They're also beginning work to see whether the treatment prevents gradual loss of vision.
At least 13 genes are known to cause Usher syndrome. Babies must have the same defective gene from each parent to develop the syndrome. One gene causes all cases in Acadians and Cajuns. Another is common in Finland and a third in Ashkenazi Jewish populations, said Mark Dunning, director of the Coalition for Usher Syndrome Research.
Each would need its own patch, called an antisense oligonucleotide, or ASO.
ASO treatments are being studied for dozens of conditions, including Duchenne muscular dystrophy, asthma and many kinds of cancer.
ASOs used in the Usher research were made by Isis Pharmaceuticals Inc., with which Hastings has a partnership.
There's no way to know when tests for a possible human treatment might begin. "We hope years rather than decades," Lentz said.
But Elise Faucheaux, of Youngsville, in Louisiana's Cajun country, has already told Lentz that she's interested in clinical trials for her son, Hunter, who is 23 months old and has Usher. Cochlear implants let Hunter hear, and therapy has enabled him to sit, stand and play normally. For now, his vision is normal.
Faucheaux said she hopes people learn about the condition so they're not blindsided after a baby's birth. She said she has a cousin with Usher but didn't know the condition was genetic until Hunter was a few months old.
"So many people around here have never heard of it," she said.
That's one of the roadblocks to early treatment. Preventing deafness would probably require diagnosing the disease in the womb rather than in early childhood or adolescence, as is usual now. People in groups with a high prevalence would have to be tested for one of the defective genes that causes Usher. If each parent had one, their fetus would be tested.
Dunning, whose 14-year-old daughter has the syndrome, was both enthusiastic and cautious about the new results: "I think it's exciting. It has the potential to really help newborn kids with Usher syndrome — if it works as we hope."