BioWorld International Correspondent
LONDON - A newly identified growth factor found in the brains of mammals has the capacity to protect the type of neurons that degenerate and die in Parkinson's disease.
The growth factor may be able to restore the function of damaged neurons, tests using an animal model of Parkinson's disease suggested, indicating that the factor may lead to new treatments for this disease.
From a purely scientific point of view, the discovery of the growth factor, which is called conserved dopamine neurotrophic factor (CDNF), also is of great interest. It is the first neurotrophic factor that has been shown to be specific for brain neurons, and that has a homologous form in invertebrate animals.
Mart Saarma, director of the Institute of Biotechnology at the University of Helsinki in Finland, told BioWorld International: "What we have discovered is a completely new group of neurotrophic factors that have been conserved in evolution. Furthermore, CDNF is the first neurotrophic growth factor that has no effect on the peripheral neurons and is specific for brain neurons."
He added, "Perhaps most importantly, the results of studies in animal models of Parkinson's disease strongly suggest that CDNF has a great potential as a therapeutic protein, and could form a new basis for the development of drugs for the treatment of Parkinson's disease."
Saarma said CDNF's ability to protect and restore the function of neurons may be helpful to brain nerve cells that degenerate and die in other diseases, too, such as Alzheimer's disease and amyotrophic lateral sclerosis. "We want to investigate this possibility," he said, "but we have not done these studies yet."
The group has patented CDNF and its use in treatment of neurodegenerative diseases. Saarma and his colleagues currently are seeking partners to help them develop their work.
A report of their study appears in the July 5 issue of Nature, titled, "Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo."
Saarma has had a long-standing interest in finding proteins that can nurture brain neurons, in the hope of developing new therapies to treat diseases in which brain neurons degenerate, such as Parkinson's disease and Alzheimer's disease.
Although neurotrophic factors that keep neurons of the peripheral nervous system alive had been characterized, researchers had identified few such factors for the central nervous system. Scientists also were surprised that no one had managed to find any neurotrophic growth factors in invertebrate animals.
More recently, other researchers had identified a neurotrophic growth factor that also acts on brain neurons, called glial cell-line-derived neurotrophic factor (GDNF). Although that appeared to be a promising potential treatment for Parkinson's disease, early clinical trials were stopped because of low efficacy and unwanted side effects.
Saarma and his colleagues set out to find new growth factors that were as effective as GDNF, but which would be better tolerated.
Having identified CDNF, they went on to examine its effect in a rat model of Parkinson's disease, in which the animals showed a movement disorder following injection of a toxin into the brain. The toxin damages the dopamine-producing nerve cells that originate in the substantia nigra of the brain and project into the striatum.
Saarma said: "We found that 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 movement disorder was normalized. When administered four weeks after the toxin, a situation mimicking a progression of the nerve degeneration in patients, injection of CDNF into the striatum was able to prevent the degeneration of dopaminergic neurons and cure the movement disorder."
Those results suggested, he added, that CDNF is a very promising new neurotrophic factor with a significant neuroprotective and neurorestorative effects on dopamine nerves in the brain.
The team is planning to carry out additional experiments using other animal models of Parkinson's disease, and to assess the toxicity of CDNF at high concentrations. "We also want to understand how the protein works, and identify its receptor," Saarma said.
Ultimately, they hope to begin clinical trials of CDNF in human patients with Parkinson's disease. Saarma suggested that it may be possible to deliver CDNF into the brain either by using a small pump to inject it straight into the brain, or by using a delivery vector such as adeno-associated virus.