Drug discovery och regeneration för Parkinsons sjukdom
- Diarienummer
- SRL10-0032
- Start- och slutdatum
- 120101-171231
- Beviljat belopp
- 9 700 000 kr
- Förvaltande organisation
- Karolinska Institutet
- Forskningsområde
- Livsvetenskaperna
Summary
Parkinson’s disease (PD) is a progressive degenerative disorder that affects midbrain dopamine (mDA) neurons resulting in the classical motor symptoms of the disease. Currently available treatments are symptomatic and do not change the course of disease. In this project we propose to develop two novel therapeutic approaches aiming at changing the course of PD: (1) Develop drugs that target proteins mutated in genetic forms of PD, such as LRRK2, or Wnt signaling (recently linked to PD by our lab and others); (2) Develop a novel cell replacement therapy (CRT) approach based on the direct reprogramming astrocytes into mDA neurons. In this project we will thus blend novel and well established techniques, such as cellular reprogramming and chemical biology, with our expertise in stem/regenerative medicine, DA neuron development, Wnt signaling and PD. Project plan: 1)"Identify/develop novel modulators of Wnt signaling to be tested in in vitro models of PD. 2)"Develop an in vitro model of PD by exposing human DA neurons from PD-iPS cells, to abnormal levels of Wnt/b-catenin or small molecules. 3)"Identify compounds and develop drugs to treat PD by performing a small molecule screen and using medicinal chemistry to develop leads into drugs and tested them in animal models of PD. 4)"Develop novel methods for PD CRT by direct reprogramming of astrocytes into mDA neurons both in vitro and in animal models of PD. Our final goal is to develop novel effective therapies for PD.
Populärvetenskaplig beskrivning
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects midbrain dopamine (DA) neurons resulting in the classical motor symptoms of the disease. Currently available treatments are symptomatic and do not change the course of disease. In this project we propose to develop two novel therapeutic approaches aiming at changing the course of PD: (1) Develop drugs that target proteins involved in PD. (2) Develop a novel cell replacement therapy approach by turning astrocytes into DA neurons by direct cell reprogramming. In this project we will thus blend novel and well established techniques, such as cellular reprogramming and chemical biology, with our expertise in stem/regenerative medicine, DA neuron development, signaling and PD. These are the different steps that we will follow: 1)"Identify/develop novel Wnt signaling modulators that will be tested in in vitro models of PD 2)"Develop an in vitro model of PD by taking advantage of human DA neurons obtained from iPS cells derived from PD patients. 3)"Identify compounds and develop drugs to treat PD by a chemical biology approach and test such drugs in animal models of PD. 4)"Develop novel methods for PD cell replacement therapy by directly reprogramming astrocytes into midbrain DA neurons. This will be performed both in a petri dish, in rodent and human cells, and in animal models of PD. Our final goal is to develop novel therapies for PD.