Global Registry and Trial Readiness

In the previous funding periods, GENOMIT formed a global registry initiative including the nationwide clinical networks of Germany/Austria/Switzerland (mitoNET), Italy (Mitocon), UK and USA,as well as the national center in Paris for the recruitment and standardized phenotyping of mitochondrial patients. The registry allows for both cross-sectional and longitudinal (by virtue of regular follow-up visits) data collection and analysis. Thus, it provides key groundwork to improve the number and quality of outcome measures and to design future clinical studies which will be feasible by increased trial readiness of patients. In the third funding period, the global registry will be joined by new countries, e.g. by the mitochondrial center of Japan (CCB) covering a very large population.

The primary aim of this work package is to use the global registry to define natural history and outcome measures for mitochondrial disorders and to enable the design of clinical trials.

This work package is coordinated by Friedrich-Baur-Institute, Dept. of Neurology, LMU Hospital Munich in cooperation with partners Klinikum rechts der Isar (IHG TUM-MED, Munich), Salzburger Landeskliniken (SALK), Institute Imagine (INSERM, Paris), Foundation IRCCS Neurological Institute C. Besta (Milan), University of Pisa, Newcastle University (WCMR) and Chiba Children´s Hospital (CCH, Chiban, Japan).

Pathomechanisms and Treatment

This work package aims to improve understanding of key molecular and biochemical mechanisms responsible for mitochondrial disease as a prerequisite for the identification of new drug targets and the development of novel treatments. Disease validation, pathophysiologic investigations, and analysis of new treatment strategies are consecutive steps to achieve this goal.

Existing cellular models will be used to evaluate the functional significance of rare gene variants. For a significant proportion of identified gene defects, no functional test is readily available. Therefore, we will develop new functional assays, which are needed to determine the function of novel disease associated genes. Such assays will permit confident determination that a rare variant in a (novel) gene is the cause of a given patient’s mitochondrial dysfunction and provide insight into new molecular pathways or the extension of known pathways.

The subproject is coordinated by Salzburger Landeskliniken (SALK), in cooperation with partners Klinikum rechts der Isar (IHG TUM-MED, Munich), Institute Imagine (INSERM, Paris), Foundation IRCCS Neurological Institute C. Besta (Milan), Newcastle University (WCMR) and Chiba Children´s Hospital (CCH, Chiban, Japan).

Global Registry and Patients

The success of the project is substantially influenced by the availability of medical data and outcome measures, which are referred by the patients themselves. Information on quality of life, experience of health care and other aspects of the patients live is important to complement the medical data but hardly to recognized in a treatment context at the clinic. Currently, there are already some national patient registries established. There is the question if the national patient registries should run in parallel or may be integrated into a global patient registry and how patient registries and clinical registries could benefit from each other. In this respect, GENOMIT will provide a platform to foster international cooperation of patient advocacy organizations (PAOs).

The focus of this work package will be on the integration of patient-reported outcomes measures (PROMs) into the global registry.

This work package is coordinated by IMP in cooperation with partners Mitocon, DGM, Lily, AMMi and supported by all other GENOMIT partners.