Crowd-funding campaign hopes to accelerate clinical trials of new brain-repair discovery

April 1, 2015

Human astrocyte-converted neurons (credit: Gong Chen Lab, from Ziyuan Guo et al./Cell Stem Cell)

Penn State scientists have started their own crowd-funding campaign to bring brain-repair research from the lab into clinical trials.

The research team recently discovered a way to transform a support brain cell — called a glial cell — into healthy, functioning neural cells to replace nerves damaged by Alzheimer’s or Parkinson’s disease, brain or spinal-cord traumas, or stroke.

The campaign’s website features videos about the research, including a video with Penn State Head Basketball Coach Patrick Chambers in which he shares the impact of such medical conditions on his own family.

Gong Chen, a professor of biology and Penn State’s Verne M. Willaman Chair in Life Sciences, directs the research team, which is working on brain and spinal-cord disorders. Their work could lead to treating a wide variety of neurological disorders including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), stroke, traumatic brain injury, spinal-cord injury, epilepsy, autism, and schizophrenia.

“Our technology is completely different from classical stem-cell therapy, where external cells that have been cultured in artificial conditions for a long time are then transplanted into the brain,” he said.

“A big problem with stem-cell therapy is that the patient’s body often rejects the foreign cells. In contrast, our technology transforms a patient’s own glial cells into functioning neurons. Our technology eliminates the possibility that the patient’s immune system will reject the transformed cells.”

This procedure only involves converting dysfunctional reactive glial cells associated with nerve injury and neurodegenerative disorders.

Penn State Eberly College of Science | From Lab Bench to Bedside: Accelerating Clinical Trials for Brain Repair USEED Video #2

Chen’s lab is also developing another revolutionary technique using small molecules to transform human glial cells into functional neurons, instead of using the viruses or other agents typically used in stem-cell therapy. It allows for drugs that can penetrate the blood-brain barrier to get inside the injured brain to help it heal.

“It is exciting to imagine that one day patients can take a daily pill to regenerate new neurons in their brains,” Chen said. “We have made an important step toward that goal, and we are hoping that support from crowd funding will help us reach that goal much more quickly.”

UPDATE April 2, 2015: Added: “This procedure only involves converting dysfunctional reactive glial cells associated with nerve injury and neurodegenerative disorders.”

Abstract of In Vivo Direct Reprogramming of Reactive Glial Cells into Functional Neurons after Brain Injury and in an Alzheimer’s Disease Model

Loss of neurons after brain injury and in neurodegenerative disease is often accompanied by reactive gliosis and scarring, which are difficult to reverse with existing treatment approaches. Here, we show that reactive glial cells in the cortex of stab-injured or Alzheimer’s disease (AD) model mice can be directly reprogrammed into functional neurons in vivo using retroviral expression of a single neural transcription factor, NeuroD1. Following expression of NeuroD1, astrocytes were reprogrammed into glutamatergic neurons, while NG2 cells were reprogrammed into glutamatergic and GABAergic neurons. Cortical slice recordings revealed both spontaneous and evoked synaptic responses in NeuroD1-converted neurons, suggesting that they integrated into local neural circuits. NeuroD1 expression was also able to reprogram cultured human cortical astrocytes into functional neurons. Our studies therefore suggest that direct reprogramming of reactive glial cells into functional neurons in vivo could provide an alternative approach for repair of injured or diseased brain.