Neurofibromatosis type 2 (NF2) is a hereditary condition most commonly associated with bilateral vestibular schwannomas (VS), also known as acoustic neuromas. These are benign tumors that occur on the nerves for balance and hearing leading to the inner ear. Although these tumors are benign, they can cause hearing and balance problems. People with NF2 also have an increased risk of other tumors of the nervous system. Now, a mouse study by scientists at Massachusetts General Hospital (MGH) and Massachusetts Eye and Ear reveals that the blood pressure drug losartan may benefit patients with NF2.
The findings are published in the journal Science Translational Medicine in a paper titled, “Losartan prevents tumor-induced hearing loss and augments radiation efficacy in NF2 schwannoma rodent models.”
“Hearing loss is one of the most common symptoms of NF2 caused by VS,” wrote the researchers. “Fibrosis in the VS tumor microenvironment (TME) is associated with hearing loss in patients with NF2. We hypothesized that reducing the fibrosis using losartan, an FDA-approved antihypertensive drug that blocks fibrotic and inflammatory signaling, could improve hearing.”
“Developing effective therapeutics to preserve hearing function in patients with NF2 is an urgent unmet medical need. The greatest barrier to managing NF2-related auditory impairment is our incomplete understanding of how schwannomas cause hearing loss,” explained co-senior author Lei Xu, MD, PhD, a researcher in the Steele Laboratories for Tumor Biology within the MGH department of radiation oncology.
Losartan is used to treat hypertension and to help protect the kidneys from damage due to diabetes. It is also used to lower the risk of strokes in patients with high blood pressure and an enlarged heart.
Using a mouse model of NF2, Xu and her colleagues found that losartan treatment had several effects on vestibular schwannomas and the brain. The researchers observed it reduced inflammatory signaling and swelling, which prevented hearing loss and it increased oxygen delivery to enhance the effectiveness of radiation therapy.
In preparation to translate these findings into the clinic, co-senior author Konstantina Stankovic, MD, PhD, former chief of the division of otology and neurotology at Massachusetts Eye and Ear, and now Bertarelli professor and chair of the department of otolaryngology—head and neck surgery at Stanford University School of Medicine, examined patient samples and data.
Her team found that vestibular schwannomas associated with poor hearing had more pronounced inflammatory signaling than tumors associated with good hearing. This inflammatory signaling in tumors was capable of directly damaging cochlear cells that are essential for hearing.
The study provides the rationale and critical data for a prospective clinical trial of losartan in patients with VS.
“As one of the most commonly prescribed drugs for hypertension, the safety and low cost of losartan warrants rapid translation of our research to patients with vestibular schwannomas to try to prevent tumor-induced sensorineural hearing loss,” Stankovic said.