NUCLEAR ENVELOPE-LINKED RARE HUMAN DISEASES: FROM MOLECULAR PATHOPHYSIOLOGY TOWARDS CLINICAL APPLICATIONS


ACRONYM

EURO-Laminopathies

PROJECT SUMMARY

Laminopathies are rare human diseases linked to mutations in genes encoding nuclear envelope proteins, such as A-type lamins (LMNA) and lamin-binding proteins (EMD, LBR, LAP2). Laminopathies are clinically manifested after birth, progressively developed during childhood or adolescence, and some laminopathies lead to early death. Efficient therapies have been hampered by the lack of understanding the molecular disease mechanisms.

Using a variety of clinical and basic research approaches the EURO-Laminopathies team meets the challenge to find out how disease-causing mutations in A-type lamins or in one of their prominent binding partners LAP2alpha affect atomic structure, interactions, and assembly properties of lamins. By means of patient cells and animal models the consortium will test how mutations or loss of LMNA, EMD, LBR or LAP2 affect chromatin organization, gene expression, and differentiation of adult muscle- and adipose stem cells. Data obtained in these systems as well as chemical compound screening using the zebrafish model system will identify potential drug targets and drugs for testing in animal disease models and for potential therapeutic intervention. Furthermore, the consortium will extend and evaluate clinical trials on the treatment of lipodystrophy-type laminopathy patients with drugs that target the adipocyte differentiation pathway, and develop theranostic tests for the validation of therapies.

FURTHER DETAILS

Applicant Medizinische Universität Wien, Austria
Coordinator Prof. Roland Foisner, Department of Medical Biochemistry
Number of partners 11 institutions with 16 partners from Austria, France, Germany, Israel, Italy, Spain, Switzerland and United Kingdom
PUNKT's responsibilities Creation of the proposal's concept, composition of the expository, organisational, administrative and financial considerations of the project, project-coordination, -organisation and -communication with all participating institutions and partners.
Status Funded and completed in 2009; LSHG-CT-2005-018690
Website www.projects.mfpl.ac.at/euro-laminopathies