Protein Fingerprinting in Cochlear Fluids of NF2 Mouse Models with Hearing Loss for Prognostic Biomarker Identification
Abstract
We propose to identify biomarkers for a better prognostic of hearing loss in patients with neurofibromatosis type 2 (NF2) and vestibular schwannomas. The hallmark of NF2 is the development of bilateral vestibular schwannomas. There are no curative therapies or clinical predictive tools for hearing loss, which is a major concern for NF2 and vestibular schwannoma (VS) patients. The size or growth rate of vestibular schwannoma is not always predictive of the extent and progression of hearing loss. Indeed, hearing loss can be associated with small tumors, progressive hearing loss with non-growing tumors or with large tumors and good hearing. These clinical observations suggest the existence of factor(s) other than size and/or growth rate of the tumor as contributing to hearing loss. Molecular and pathological studies have demonstrated the presence of elevated protein content and/or protein precipitates in the inner ear of vestibular schwannoma patients. To identify hearing loss biomarkers we will use two NF2 mouse models, both presenting with progressive hearing loss. In the two models, however, mechanisms leading to hearing loss are different: one mouse model presents hearing loss with no schwannoma of the acoustic nerve, but massive protein precipitates. The other mouse model presents hearing loss in association with schwannoma development. These unique preclinical tools will allow us to dissect the different factors leading to hearing loss. We detected protein precipitates in the inner ear (cochlea), so we will collect the inner ear fluids of the different mouse models and their respective controls. Mass spectrometry will be used to identify the proteins in the samples. By comparing the different samples from inner ear, cerebrospinal fluid, and blood in the different models, we will be able to identify biomarkers of hearing loss associated or not with vestibular schwannoma. Finally, the identified biomarkers will be validated in mouse and human inner ear sections. The innovation of this proposal relies on the use of molecular techniques such as mass spectrometry and two NF2 mouse models with different hearing loss mechanisms to dissect the causes of the hearing loss in VS patients. This project will lead to the identification of biomarkers to be used in the clinic to predict the onset and/or progression of hearing loss in NF2 and VS patients. In the long term, these newly identified biomarkers could also be used as targets for therapeutic approaches for the treatment of hearing loss.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810622
Entities
People
- Jeremie Vitte
Organizations
- United States Army
- University of California, Los Angeles