Funded Studies
Objective/Rationale:
A characteristic feature of Parkinson’s disease is the loss of axons, the long processes of neuronal cells. This loss of axons seems to occur early in the course of the disease and very likely precedes the death of neurons. In our earlier studies we have identified a molecule, ROCK, which is important for axonal regeneration and neuronal survival. Blocking of ROCK by viral vectors or pharmacological substances increased axonal regeneration and neuronal survival in cell culture models.
Project Description:
In our experiments we will use two common pre-clinical models of PD: the MPTP- and the 6-OHDA model. These models result in axonal degeneration and neuronal cell death, which is similar to what is seen in PD patients. Models will be treated with viral vectors or pharmacological substances in order to inhibit ROCK and we will quantify motoric behaviour, levels of neurotransmitters and numbers of surviving neurons after treatment. In addition, we will test these substances in cell culture models of PD. We will also evaluate the distribution of ROCK in PD brains.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Inhibition of axonal degeneration and promotion of axonal regeneration may be a future therapeutic target, especially for the early stages of Parkinson’s disease. Many experimental therapies so far have targeted neuronal cell death, which is probably too late to reverse the disease. Targeting ROCK may address the course of the disease at an earlier point in time and may thus be more promising.
Anticipated Outcome:
At the end of this project we would like to answer the question whether inhibition of ROCK is a promising pharmacological target for the treatment of Parkinson’s disease. Since some ROCK inhibitors are already in clinical use for other applications, a positive outcome may warrant the testing of these substances in a pilot study with PD patients.
Progress Report
The protein Rho Kinase (ROCK) negatively influences the course of various traumatic diseases of the central nervous system by inhibiting the outgrowth of lesioned nerve cells. We have studied its contribution to disease development in Parkinson’s disease (PD). Examinations of human brain tissue suggest that ROCK protein is increasedly expressed in brain regions which are known to degenerate in human PD. Furthermore, we have studied the possible use of substances, which inhibit the function of ROCK in cell culture and in pre-clinical models. Nerve cells in culture grow and survive better when ROCK inhibitors were applied. Interestingly, we have also found that application of a ROCK inhibitor can protect nerve cell bodies and their fibers from neurodegeneration in pre-clinical models of PD. Thus, a more detailed analysis of the therapeutic potential of these substances may provide a basis for later therapy development for human PD.
May 2012