Neuron Transformation In The Brain Opens A New Avenue In Neurobiology
January 21, 2013

Neuron Transformation Technique Could Lead To New ALS Treatments

redOrbit Staff & Wire Reports - Your Universe Online

A pair of Harvard University stem cell biologists have reportedly demonstrated a technique with which they can transform one type of already differentiated neuron into another.

The discovery, reported by the Cambridge, Massachusetts-based Ivy League school in a statement released Sunday, demonstrates it is possible that the human brain “is not as immutable as we always thought, because at least during an early window of time one can reprogram the identity of one neuronal class into another,” said Paola Arlotta, an Associate Professor in Harvard's Department of Stem Cell and Regenerative Biology (SCRB) and one-half of the research team.

Previously, Doug Melton, co-chair of the SCRB and co-director of the Harvard Stem Cell Institute (HSCI), and colleagues demonstrated the principles of direct lineage reprogramming of differentiated cells within the body, the university explained.

Melton´s team managed to take exocrine pancreatic cells and alter them so they became insulin-producing beta cells, and now Arlotta and colleague Caroline Rouaux have applied those findings to neurons in research published online this weekend in the journal Nature Cell Biology.

“In their experiments, Arlotta targeted callosal projection neurons, which connect the two hemispheres of the brain, and turned them into neurons similar to corticospinal motor neurons, one of two populations of neurons destroyed in Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease,” the university explained.

“To achieve such reprogramming of neuronal identity, the researchers used a transcription factor called Fezf2, which long has been known for playing a central role in the development of corticospinal neurons in the embryo,” they added. “What makes the finding even more significant is that the work was done in the brains of living mice, rather than in collections of cells in laboratory dishes.”

However, the mice used in the experiments were young, so to this point Arlotta and Rouaux are not sure whether or not the neuron reprogramming process can be applied to older laboratory animals — or to humans, for that matter. If it proves possible, though, it could ultimately lead to new treatment options for ALS or other neurodegenerative conditions, the researchers report.

"Neurodegenerative diseases typically effect a specific population of neurons, leaving many others untouched. For example, in ALS it is corticospinal motor neurons in the brain and motor neurons in the spinal cord, among the many neurons of the nervous system, that selectively die," Arlotta said.

"What if one could take neurons that are spared in a given disease and turn them directly into the neurons that die off? In ALS, if you could generate even a small percentage of corticospinal motor neurons, it would likely be sufficient to recover basic functioning,” she added. "My hope is that this will facilitate work in a new field of neurobiology that explores the boundaries and power of neuronal reprogramming to re-engineer circuits relevant to disease.”