In a major breakthrough, NOMIS Awardee Don W. Cleveland and colleagues have identified a potentially powerful and chemically feasible approach to treating Parkinson’s disease by replacing lost neurons. Their findings were published in Nature.
June 24, 2020
Xiang-Dong Fu, PhD, has never been more excited about something in his entire career. He has long studied the basic biology of RNA, a genetic cousin of DNA, and the proteins that bind it. But a single discovery has launched Fu into a completely new field: neuroscience.
Several years ago, a postdoctoral researcher working in Fu’s lab was taking that approach, using a technique called siRNA to silence the PTB gene in connective tissue cells known as fibroblasts. But it’s a tedious process that needs to be performed over and over. He got tired of it and convinced Fu they should use a different technique to create a stable cell line that’s permanently lacking PTB. At first, the postdoc complained about that too, because it made the cells grow so slowly.
But then he noticed something odd after a couple of weeks — there were very few fibroblasts left. Almost the whole dish was instead filled with neurons.
In this serendipitous way, the team discovered that inhibiting or deleting just a single gene, the gene that encodes PTB, transforms several types of mouse cells directly into neurons.
More recently, Fu and Hao Qian, PhD, another postdoctoral researcher in his lab, took the finding a big step forward, applying it in what could one day be a new therapeutic approach for Parkinson’s disease and other neurodegenerative diseases. Just a single treatment to inhibit PTB in mice converted native astrocytes, star-shaped support cells of the brain, into neurons that produce the neurotransmitter dopamine. As a result, the mice’s Parkinson’s disease symptoms disappeared.
Continue reading this UC San Diego release
Read the Nature article: “Reversing a model of Parkinson’s disease with in situ converted nigral neurons”
Read the Financial Times’ report on the findings: “Neuron breakthrough raises hopes for possible Parkinson’s treatment”
Don W. Cleveland
Head of the Laboratory for Cell Biology at the Ludwig Institute for Cancer Research in San Diego.
Ludwig Cancer Research
Mechanisms of Gene Silencing and Liquid-Liquid De-mixing in the Nervous System
NOMIS RESEARCH PROJECT