Research team
Identification of molecular players and drug targets for DICMTC neuropathy.
Abstract
Charcot-Marie-Tooth disease (CMT) is the most common inherited neuromuscular disorder, affecting 1/2500 individuals worldwide. The main symptoms are progressive distal muscle weakness and wasting, sensory loss, reduced tendon reflexes, and foot and hand deformities. More than 500 mutations in over 40 genes have been implicated with this type of pathology providing more accurate CMT diagnosis. However, no effective therapies are available to treat CMT patients. Dominant intermediate CMT type C (DI-CMTC) is a recently defined CMT entity, characterized by axonal degeneration and demyelination of peripheral neurons. We were the first to describe DI-CMTC and demonstrated that it is caused by specific mutations in the gene encoding for tyrosyltRNA syntethase (YARS). This application is focused on the identification of molecular players and potential drug targets for this particular subtype of CMT. We will perform a screen for genetic modifiers of neurodegenerative phenotypes present in our recently generated Drosophila DI-CMTC model. The targeted genes will be selected based on their predicted abilities to interact with drug-like compounds. In this way, we will be able to gain original knowledge on DI-CMTC pathomechanisms and to translate it into a rational and reliable drug discovery program for this and possibly other inherited and acquired neuropathies.Researcher(s)
- Promoter: Jordanova Albena
- Co-promoter: Timmerman Vincent
- Fellow: Ermanoska Biljana
Research team(s)
Project type(s)
- Research Project
Identification of molecular players and drug targets for DI-CMTC neuropathy.
Abstract
Charcot-Marie-Tooth disease (CMT) is the most common inherited neuromuscular disorder, affecting 1/2500 individuals worldwide. The main symptoms are progressive distal muscle weakness and wasting, sensory loss, reduced tendon reflexes, and foot and hand deformities. More than 500 mutations in over 40 genes have been implicated with this type of pathology providing more accurate CMT diagnosis. However, no effective therapies are available to treat CMT patients. Dominant intermediate CMT type C (DI-CMTC) is a recently defined CMT entity, characterized by axonal degeneration and demyelination of peripheral neurons. We were the first to describe DI-CMTC and demonstrated that it is caused by specific mutations in the gene encoding for tyrosyltRNA syntethase (YARS). This application is focused on the identification of molecular players and potential drug targets for this particular subtype of CMT. We will perform a screen for genetic modifiers of neurodegenerative phenotypes present in our recently generated Drosophila DI-CMTC model. The targeted genes will be selected based on their predicted abilities to interact with drug-like compounds. In this way, we will be able to gain original knowledge on DI-CMTC pathomechanisms and to translate it into a rational and reliable drug discovery program for this and possibly other inherited and acquired neuropathies.Researcher(s)
- Promoter: Jordanova Albena
- Fellow: Ermanoska Biljana
Research team(s)
Project type(s)
- Research Project