Is the treatment of Parkinson's disease possible with a new neurotrophic factor in the future?

July 04, 2007

Parkinson's disease is a degenerative brain disease characterized by the loss of dopamine neurons in the midbrain-area called Substantia Nigra. The research group led by professor Mart Saarma, Director of the Institute of Biotechnology, University of Helsinki, has discovered a novel neurotrophic factor CDNF (Conserved Dopamine Neurotrophic Factor). CDNF was shown to protect and even rescue damaged dopamine neurons in an experimental model of Parkinson's disease in studies performed by the research group of professor Raimo K. Tuominen, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. More importantly, also the function of the neurons was recovered after an experimental lesion of the dopamine neurons in Substantia Nigra.

The findings of this research may be of great importance for the development of new treatment strategies for Parkinson's disease. The results of this study will be published in "Nature" on July 5th, 2007.

Approximately one percent of people aged over 60 get Parkinson's disease all over the World. The demographic change with increasing number of elderly people will lead in doubling of the number of Parkinsonian patients also in Finland during 2005 - 2030. Typical symptoms in Parkinson's disease are those of muscle rigidity, tremor, and slowness of movement. They are a consequence of the degeneration of dopamine nerves projecting from Substantia Nigra to Caudate Putamen (also called Striatum). The clinical symptoms manifest when approximately 70 % of the dopamine nerves have been destroyed. Degeneration of the dopamine nerves progresses slowly, and in time the difficulties in movement becomes a major factor reducing the quality of life of these patients.

Current drug treatment of Parkinson's disease aims at increasing dopamine concentration and / or activation of dopamine receptors in the brain. Due to the progression of the nerve degeneration the drug therapy gradually becomes less effective. Neurotrophic factors which could slow down or even halt the progression of the degeneration of dopamine nerves have been in the focus as a possible new treatment for Parkinson's disease. Glial cell- line derived neurotrophic fctor (GDNF) is one example of such a promising growth factor. Indeed, it was shown to have beneficial effects in a clinical trial in Parkinsonian patients suffering from severe symptoms. However, due to adverse effects the clinical trials have been stopped, even though some of the patients would have continued the therapy. Even so, the clinical trials on GDNF gave the proof of concept for the use of neurotrophic factorstreatment of neurodegenerative diseases. Therefore it is very important to search for new growth factors with similar efficacy as GDNF, but with better tolerability.

Conserved dopamine neurotrophic (CDNF) factor discovered and characterized in this study is well conserved in the evolution. It belongs to a CDNF/MANF family of proteins, which is the first evolutionarily conserved family of neurotrophic factors having a representative also in invertebrate animals (MANF = mesencephalic astrocyte derived neurotrophic factor).

In an experimental model of Parkinson's disease, a neurotoxin 6-OHDA was injected on one side of the brain into the striatum of rats. This toxin causes a progressive degeneration of dopamine nerves similar to that observed in Parkinsons disease. Upon activation of dopamine nerves of the brain by drugs, these animals show a movement disorder, a circling behaviour, which reflects an imbalance of dopamine activity of the brain hemispheres.

A single injection of CDNF six hours before the toxin delivery into the striatum significantly prevented the degeneration of dopamine nerves in the brain and also the turning behavior was normalized. When administered four weeks after the toxin, situation mimicking a progression of the nerve degeneration in patients, injection of CDNF into Striatum was able to prevent the degeneration of dopaminergic neurons and cure the behavioral imbalance.

The results of the present study show that CDNF is a very promising new neurotrophic factor with a significant neuroprotective and neurorestorative effects on dopamine nerves in the brain. It may have significant potential in the treatment of Parkinson's disease in the future as a neuro protective or even neurorestorative therapy.
Title of the article in "Nature": Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo

Authors: Päivi Lindholm1, Merja H. Voutilainen2, Juha Laurén1†, Johan Peränen1, Veli-Matti Leppänen1, Jaan-Olle Andressoo1, Maria Lindahl1, Sanna Janhunen2#, Nisse Kalkkinen1, Tõnis Timmusk1,3, Raimo K. Tuominen2 & Mart Saarma1

Ms. Päivi Lindholm, M.Sc., had a central role in the discovery of CDNF and Mrs. Merja H. Vuotilainen (born Kauppinen), M.Sc. performed the studies on experimental model of Parkinson's disease.

For further information, please contact:

Prof. Mart Saarma (050 5002726)
Prof. Raimo K. Tuominen 050 5548005)
M.Sc. Päivi Lindholm (040 5239884)
M.Sc. Merja H. Voutilainen (050 4002191)

University of Helsinki

Related Neurons Articles from Brightsurf:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.

Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.

A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.

Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.

Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.

Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.

The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.

Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.

How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.

Read More: Neurons News and Neurons Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to