Around 12 in 1000 people in the world will have balance issues and hearing loss due to a condition called Meniere´s disease (MD). The cause of Meniere´s disease is unknown. It typically begins with vertigo attacks in young adults and then leads to hearing loss in thirties or forties. Symptoms vary between people and over time. The main problems are unpredictable attacks of vertigo that can last from a few minutes to 24 hours. Consequently, Meniere´s disease is an unpredictable and distressing illness. Currently the only treatment is reducing and controlling symptoms (anti-vertigo medications and hearing aids). Moreover, there is no specific test that, on its own, is reliable in diagnosing Meniere’s disease and the symptoms overlap with many other illnesses. So the final diagnosis normally takes several months or even years.
The problems of treatment and diagnosis are due to the fact that Meniere's disease is complex and the underlying causes are unknown. Many factors are thought to be involved in the development of the condition, such as increased pressure of fluid in the inner ear. There is an inherited component - and some candidate defective genes have been identified in families with the disease. It is thought that environmental triggers are also important. The relationship between these factors and the progression of the disease however remains unclear. Unfortunately, despite many efforts to understand the genetic and molecular basis of the disease, results remain limited due to the absence of a suitable in vivo model.
The worldwide incidence suggests that around 100,000 patients develop MD every year. But MD is complex and difficult to diagnose. Currently treatment is confined to treating symptoms. Lack of understanding of basic aetiology impairs rational progress in diagnosis and treatment.
MD is considered a debilitating disease that interferes with the activities of daily living and imposes substantial costs to national health systems due to the lack of effective treatment. Overall, the use of animal models of MD will enable understand of cells, pathways and trigger involve in MD and could open several lines of translational research including a novel research field focus on discovering of new target and more accurate drugs to beneficial the patient health.
The goal of FLYMEN is to create a new animal model for MD, with the fruit fly (Drosophila), and thereby identify pathways involved in the MD-associated decline of auditory and vestibular function and to probe the interactions between genetic and environmental factors. To this end, I will pursue three major aims: 1) Does the deletion of key genes in Drosophila produce hearing loss and/or vestibular phenotypes with similarities with human MD? 2) What is the basis of MD-related degeneration? This will be assessed by expression and morphological analyses of mutants. 3) Do environmental factors trigger or enhance MD-related degeneration?
Conclusions of the action
The FLYMEN project has investigated the role of several MD candidate genes inside the Drosophila ear, biased towards pathway or molecular discovery and consequently a treatment. The exploration of these genes in Drosophila resulted in first animal model with MD-like phenotype without any drug conditioning knocking out the Dyb gene. In addition we are generated a Dyb-GFP enhancer transgenic reporter line that has allow the identification of cells involved.
