Getting to the stem of a chronic problem
Findings by leading European scientists, published in the latest issue of Cell, reveal critical factors determining the onset of Parkinson's disease. The results, researchers say, could prove very useful in developing stem cell therapies aimed at beating this debilitating brain disease.
Researchers at the Karolinska Institute in Sweden discovered something called a “master determinant” in the transformation of mouse embryonic stem cells into bona fide dopamine neurons, brain cells that degenerate in patients with Parkinson's disease. The findings show promise in future cell replacement therapy for this incurable condition sometimes described as ‘shaking palsy', say the study's senior authors, Johan Ericson and Thomas Perlmann.
“The use of cell replacement therapy in the treatment of Parkinson's disease is fraught with … problems,” Perlmann said in a statement. “However, clinical trials have provided important proof of principle that transplantation of dopamine neurons might work in patients.”
“Ethical and practical issues associated with transplantation of foetal dopamine neurons to patients with Parkinson's disease have triggered intense interest in the [possible] use of in vitro-engineered stem cells as an unlimited cellular source for transplantation,” Ericson says. So, the scientists set out to establish whether dopamine neurons could be generated artificially from stem cells. For this, they studied the genes expressed by the dopamine progenitor cells in the developing midbrains of embryonic mice.
The scientists are confident that these are authentic dopamine neurons. This, they stress, is critical to treating Parkinson's patients with stem cells. “[It] is of utmost importance to make the correct cell type,” says Perlmann. Complicating matters for the team, there are at least 1 000 different types of neurons in the brain, only one of which is clinically relevant to Parkinson's disease.
“Our data establish Lmx1a and Msx1 as critical intrinsic dopamine-neuron determinants, in vivo, and suggest that they may be essential tools in cell replacement strategies in Parkinson's disease,” the researchers conclude.
Further study will show whether stem cell-derived neurons will work in treating rats with Parkinson's disease. And follow-up tests will establish whether these findings in animals will hold for humans as well. The authors of the Cell paper acknowledge their contributors and funding organisations, which include the Swedish National Research Council, the Michael J Fox Foundation – set up by the American actor who suffers from Parkinson's – and the European Community through network funding and a Fifth Framework Programme (FP5) project grant.
The recently concluded three-year EU research project, called Brainstem Genetics, investigated the genetic component in brainstem development and function. Consortium scientists from Norway, Sweden, France and the UK, including those from the Karolinska Institute's department of cell and molecular biology, looked into how the brain stem regulates vital functions involved in major chronic health problems, from sleep and mood disorders through to serious conditions, such as neurodegenerative conditions and tumours.Cell, Karolinska Institute
Cell (Elsevier Inc.)
Brainstem Genetics (FP5 on CORDIS)
Johan Ericson and Thomas Perlmann (Karolinska Institute's Department of Cell and Molecular Biology)