We propose to characterize different motorneuron cell lines obtained from the induction of pluripotent stem cells as well as the validation of a unique cell model for ALS based on the use of lymphoblasts from patients who are well characterized genetically.

In these models, we shall study the recuperation of the proteostatic equilibrium upon treatment with specially designed small molecule modulators. We will place special emphasis on the determination of the levels of autophagy, mitophagy, oxidative stress, and neuroinflammation as well as the phosphorylation and (mis)localization of TDP43, whose aggregates are a hallmark of this pathology.

The evaluation of different innovative drugs prepared during this project; namely, inhibitors of various protein kinases, activators of Nfr2 antioxidants, modulators of mitophagy, etc. in the different genetically characterized cellular models, will allow us to design a personalized treatment strategy for each group of ALS patients in order to optimize the therapeutic benefit.

The best drug candidates found in human cell models will be evaluated in vivo using transgenic models overexpressing TPD43, in order to increase their success in the final translation to patients. This program also contemplates the study of the efficacy of Tideglusib, a protein kinase inhibitor from our laboratories which is currently in clinical development, both in these cellular models as well as in a small number of patients for a possible repositioning for the treatment of ALS.

 
  • To provide and characterize cell models based on human samples from patients for the study of ALS

 

  • Design and development of therapeutic agents able to modulate TDP43 homeostasis

 

 

  • Validation of the efficacy of drug candidates for ALS

 

 

  • Tideglusib repurpoising for ALS

     

 

 

CONTACTO:


 


 

 Coordinadora:

Ana Martínez (This email address is being protected from spambots. You need JavaScript enabled to view it.)

Gestora del Proyecto:

Nuria Mª Rivas (This email address is being protected from spambots. You need JavaScript enabled to view it.)

Centro de Investigaciones Biológicas (CIB-CSIC)

C/Ramiro de Maeztu, 9

28006 MADRID

 

 

 

 

 

 

             Proyecto ELA-MADRID.B2017/BMD-3813

 

 Proyecto financiado por la Comunidad de Madrid y la Unión Europea