CDNF (Cerebral Dopamine Neurotrophic Factor) for Therapy of Parkinson's Disease
Neurotrophic Factor Therapies for Parkinson's Disease, 2010
CDNF protein is expressed in human brain, acts differently from known neurotrophic factors and can protect and repair dopamine neurons in two pre-clinical models of Parkinson’s disease (PD). Another neurotrophic factor, GDNF, that acts via classical neurotrophic mechanism, has been effective in several pre-clinical models of PD and had some efficacy in parkinsonian patients. Now we want to compare the effects of CDNF and GDNF in the treatment of experimental PD in two different pre-clinical models.
The effects of CDNF and GDNF will be compared in two pre-clinical models of Parkinson’s disease. In the first pre-clinical we induce degeneration of dopamine neurons by injecting the neurotoxin 6-OHDA. In the second, we use MPTP to cause damage to dopamine neurons. After 6-OHDA or MPTP injections we wait four weeks in order to let the damage of dopamine neurons to reach similar severity as is found in parkinsonian patients. Then we infuse placebo, CDNF and GDNF into both models. Our aim is to compare the effects of CDNF and GDNF on behavior, functional activity of dopamine neurons in vivo, and number of dopamine neurons.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Presently the treatments of Parkinson’s disease are focused on alleviating the motor symptoms of the disease. The effect of these drugs, e.g. levodopa, is good as long as there are sufficient number of dopamine neurons in the brain. However, the dopamine neuron damage is progressive in time and the effect of levodopa is diminished. CDNF treatment could possibly halt the destruction and improve the functional activity of dopamine neurons thereby potentiating levodopa treatment.
We are enthusiastic to see whether CDNF that acts by different mechanism than GDNF, is as effective as GDNF in the pre-clinical models we use. If this is the case, or if CDNF is even better than GDNF, we will start the toxicity studies to evaluate safety of CDNF. If the safety profile of CDNF is favorable, we will go on to start with first human administration of CDNF to parkinsonian patients.
Academy Professor at University of Helsinki
Location: Helsinki, Finland