On Christmas Eve, 2002, Bryce Faber was diagnosed with a deadly cancer called neuroblastoma. The 2-year-old’s treatment, which, in addition to surgery, included massive amounts of radiation followed by even more massive amounts of antibiotics, no doubt saved his life. But those same mega-doses of antibiotics, while staving off infections in his immunosuppressed body, caused a permanent side effect: deafness.
“All I remember is coming out of treatment not being able to hear anything,” said Bryce, now a healthy 14-year-old living in Arizona. “I asked my mom, ‘Why have all the people stopped talking?’” He was 90 percent deaf.
“The loss has been devastating,” said his father, Bart Faber. “But not as devastating as losing him would have been.”
Treatment with aminoglycosides, the most commonly used class of antibiotics worldwide, is often a lifesaving necessity. But an estimated 20-60 percent of all patients who receive these antibiotics suffer partial or complete hearing loss.
Now, in a study published online in the Journal of Clinical Investigation, researchers at the Stanford University School of Medicine report that they have developed a modified version of an aminoglycoside that works effectively in mice without the risk of causing deafness or kidney damage, another common side effect.
The researchers hope to test versions of the modified antibiotic in humans as soon as possible.
“If we can eventually prevent people from going deaf from taking these antibiotics, in my mind, we will have been successful,” said Anthony Ricci, PhD, professor of otolaryngology-head and neck surgery and co-senior author of the study. “Our goal is to replace the existing aminoglycosides with ones that aren’t toxic.”
Four years in the making
It took the scientists four years of research to produce 5 grams of the newly patented antibiotic, N1MS, which is derived from sisomicin, a type of aminoglycoside.
N1MS cured urinary tract infection in mice just as well as sisomcicin, but did not cause deafness, study results show. The study presents a promising new approach to generating a new class of novel, nontoxic antibiotics, Ricci said.
The two senior authors – Ricci and Alan Cheng, MD, associate professor of otolaryngology-head and neck surgery – joined forces in 2007 to explore the idea of creating new and improved versions of these antibiotics based on a simple yet groundbreaking idea born of Ricci’s basic science research into the biophysics of how hearing works within the inner ear.
Other Stanford co-authors are postdoctoral scholars Markus Huth, MD, Yi-Ju Hsieh, PhD, Thomas Effertz, PhD, Kyu-Hee Han, MD, and Sarah Verhoeven, MD; research assistants Kayvon Sotoudeh and Andrew Vu, MD; Michael Hsieh, MD, PhD, assistant professor of urology; and SPARK chemistry consultant Robert Greenhouse, PhD.
The study was funded by the National Institutes of Health (grants P30DC010363, K08DK087895, K08DC011043, R21DC012183, RO1DC003896 and RO1DC013910), the Swiss National Science Foundation, the Jerry Yang Faculty Scholar Fund and SPARK.