Can brain cells be reprogrammed to make dopamine?
By Ilene Schneider
Almost one million people in the U.S. suffer from Parkinson’s disease, a chronic and progressive movement disorder that has no cure. It involves the malfunction and death of neurons in an area of the brain called the substantia nigra, according to the Parkinson’s Disease Foundation.
Sometimes, the dying neurons make dopamine, which sends messages to the part of the brain that controls movement and coordination. As the disease gets worse, the dopamine production decreases, and the person is unable to control his or her movements normally.
Help may be on the way. Scientists at the Karolinska Institute in Stockholm, Sweden, have reprogrammed brain cells in mice to make dopamine, thus correcting some of the movement disorders involved in Parkinson’s disease.
According to the study, “Induction of functional dopamine neurons from human astrocytes and mouse astrocytes in a Parkinson’s disease model,” published Monday in Nature Biotechnology, the procedure changed brain cells called astrocytes into cells that produce dopamine, a neurotransmitter responsible for movement. Parkinson’s disease destroys neurons that produce dopamine. If the neurons can be replaced, the researchers believe that the symptoms of the disease can be alleviated.
As the abstract explained, “Cell replacement therapies for neurodegenerative disease have focused on transplantation of the cell types affected by the pathological process. Here we describe an alternative strategy for Parkinson’s disease in which dopamine neurons are generated by direct conversion of astrocytes.”
The researchers, with Ernest Arenas as senior author and Pia Rivettidi Val Cervo as first author, used mice that had had their dopamine-producing neurons destroyed. Using a viral delivery system, they transferred three genes to the astrocytes to reprogram into cells that would produce dopamine. With three transcription factors – NEROD1, ASCL1 and LMX1A – and the micro RNA miR218, they could reprogram the human astrocytes in vitro and the mouse astrocytes in vivo, to induce dopamine neurons.
The study concluded, “The next steps to be taken toward achieving this goal include improving reprogramming efficiency, demonstrating the approach on human adult striatal astrocytes, developing systems to selectively target human striatal astrocytes in vivo and ensuring safety and efficacy in humans. With further optimization, this approach may enable clinical therapies for Parkinson’s disease by delivery of genes rather than cells.”
While Parkinson’s disease researcher Andres Bratt-Leal, director of research at the Summit for Stem Cell Foundation in San Diego, believes the approach is worth investigating, the thinks that much more needs to happen before considering it for patients. His organization’s project of reprogramming skin cells from Parkinson’s patients into pluripotent stem cells, maturing them into dopamine-producing neurons and implanting them into the brains of patients is closer to clinical testing, he said in an article in the San Diego Tribune.
“Gene therapy is promising, but there remain a lot of questions before it is ready for clinical trials,” Bratt-Leal concluded.