Neurofibromatosis type 2 (NF2), a rare genetic disorder that causes tumors to develop in the sheath of the cranial and spinal nerves, often can lead to facial paralysis, among other comorbidities. But work being done at the Neural Tumor Research Laboratory in the UCLA Department of Head and Neck Surgery is making significant progress to identify pharmacological approaches to controlling these tumors.
NF2 tumors, known as schwannomas, usually are benign. They most often form in the acoustic nerve and affect hearing and balance. “Because of the acoustic nerve’s proximity to the facial nerve, the facial nerve can become compressed, leading to facial paralysis,” explains Marco Giovannini, MD, PhD, director of the Neural Tumor Research Laboratory and scientific director of the UCLA multidisciplinary NF2 clinic.
Surgery has been the mainstay of NF2 treatment, but it carries significant risks, including the potential for resulting in neurological deficits, facial palsy and hearing loss. Dr. Giovannini’s lab is exploring whether or not drugs that are FDA-approved for other indications could, based on what is known about the molecular pathogenesis of these tumors, stop them from growing, or even shrink them.
The progress being made by Dr. Giovannini and his colleagues is due, in large part, to their development of genetically engineered mouse models of NF2. This has allowed them to screen a large number of compounds in order to inform clinical trials. They have completed one such trial, using a molecule that was FDA-approved for other oncologic indications. They tested the drug in 12 patients and found that after a year of treatment, about half of the patients showed stabilization of tumor growth.
“We have a pipeline of drugs that we will be selecting for clinical trials,” Dr. Giovannini says. “Getting one or more drugs approved for use in patients with NF2 would be a huge advance in reducing the risk of neurological deficits potentially associated with surgery by delaying the necessity for surgical intervention. It also will provide an option for patients who either wouldn’t be surgical candidates or who don’t want surgery.”
The UCLA NF2 clinic was recently established as a resource for NF2 patients to see specialists in a multidisciplinary setting. The core team includes pediatric and adult neuro-oncologists, neurosurgeons, neuro-otologists and clinical geneticists.