Towards personalized medicine in Ménière's disease

F1000Res. 2018 Aug 15:7:F1000 Faculty Rev-1295. doi: 10.12688/f1000research.14417.1. eCollection 2018.

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.

Keywords: Meniere disease; genomics; molecular genetics; precision medicine; sensorineural hearing loss; tinnitus; vertigo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Genetic Testing / methods
  • Genetic Therapy / trends
  • Hearing Loss, Sensorineural / genetics
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Meniere Disease / diagnosis
  • Meniere Disease / genetics
  • Meniere Disease / pathology
  • Meniere Disease / therapy*
  • Molecular Targeted Therapy / methods
  • Molecular Targeted Therapy / trends
  • Precision Medicine / methods*
  • Precision Medicine / trends

Substances

  • Immunosuppressive Agents

Grants and funding

Jose A. Lopez-Escamez is supported by the Luxembourg National Research Fund (grant INTER/Mobility/17/11772209), Ménière’s Society (UK), Instituto de Salud Carlos III (grant PI17/01644), and FEDER Funds and H2020 Marie Skłodowska-Curie Actions (ITN-2016–722046) from the EU.