Towards personalized medicine in Ménière’s disease

Abstract

Ménière’s disease (MD) represents a heterogeneous group of relatively rare disorders with three core symptoms: episodic vertigo, tinnitus, and sensorineural hearing loss involving 125 to 2,000 Hz frequencies. The majority of cases are considered sporadic, although familial aggregation has been recognized in European and Korean populations, and the search for familial MD genes has been elusive until the last few years. Detailed phenotyping and cluster analyses have found several clinical predictors for different subgroups of patients, which may indicate different mechanisms, including genetic and immune factors. The genes associated with familial MD are COCH, FAM136A, DTNA, PRKCB, SEMA3D, and DPT. At least two mechanisms have been involved in MD: (a) a pro-inflammatory immune response mediated by interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNFα), and IL-6, and (b) a nuclear factor-kappa B (NF-κB)-mediated inflammation in the carriers of the single-nucleotide variant rs4947296. It is conceivable that microbial antigens trigger inflammation with release of pro-inflammatory cytokines at different sites within the cochlea, such as the endolymphatic sac, the stria vascularis, or the spiral ligament, leading to fluid imbalance with an accumulation of endolymph. Computational integration of clinical and “omics” data eventually should transform the management of MD from “one pill fits all” to precise patient stratification and a personalized approach. This article lays out a proposal for an algorithm for the genetic diagnosis of MD. This approach will facilitate the identification of new molecular targets for individualized treatment, including immunosuppressant and gene therapy, in the near future.

Single Cell and Single Nucleus RNA-Seq Reveal Cellular Heterogeneity and Homeostatic Regulatory Networks in Adult Mouse Stria Vascularis

“…In a similar fashion, single cell and single nucleus transcriptome profiles, like the resource we have developed for the adult SV, might be utilized to associate cell types to inner ear diseases. For example, in Meniere's disease, while no single gene has been conclusively implicated in the disease, the association of gene mutations with cell type-specific expression might provide some clues to the involved cell type or types (Chiarella et al, 2015;Lopez-Escamez et al, 2018). Mutations in both Kcne1 and Esrrb have been identified in patients with Meniere's disease (Lopes et al, 2016;Dai et al, 2019;Gallego-Martinez et al, 2019).…”

Current Understanding and Clinical Management of Meniere's Disease: A Systematic Review

“…The vertigo disappears, sometimes leaving a residual feeling of dizziness or unsteadiness as vestibular hypofunction ensues. 2,24 The active or intermediate phase has an average duration of years. The SNHL progression starts, greater at low frequencies, with a fluctuating course.…”

Three-Dimensional Magnetic Resonance Imaging Reveals the Relationship Between the Control of Vertigo and Decreases in Endolymphatic Hydrops After Endolymphatic Sac Drainage With Steroids for Meniere's Disease

“…Its pathology was first reported in 1938 to be endolymphatic hydrops (EH) through two well-known temporal bone studies (1, 2). Recently, some genes involved in immune responses have been associated with clinical phenotypes of MD, MICA, and TLR10 are associated with hearing loss progression in patients with MD and the common variant rs11096955 in the TLR10 gene has been linked to the progression of hearing loss in patients with bilateral MD (3). Li et al used a molecular network-based method using a random walk with restart algorithm to predict genes potentially involved in MD (4) and found two common allelic variants in the NFKB1 gene (rs3774937 and rs4648011) to be associated with hearing loss progression in patients with MD.…”