By Emily Leclerc | Waisman Science Writer
After more than two decades at the Waisman Center, University of Wisconsin and several first-in-the-world stem cell scientific breakthroughs, Su-Chun Zhang, MD, PhD, professor of neuroscience and neurology, is retiring. He came to the Waisman Center in 2001 as part of the Translational Research-Neurodegenerative Diseases Cluster. Zhang anchored Waisman’s stem cell research program and has been an innovative pioneer in the field ever since.
While Zhang is leaving UW-Madison, he will continue to work with his company BrainXell (pronounced brain cell) on developing a potential treatment for Parkinson’s disease, a degenerative neurological condition, which is based in his many years of research at Waisman.
Before coming to Waisman and UW-Madison, Zhang was a physician, but he had always been interested in research pursuits with more direct translation to patients. Stem cells proved to be an excellent avenue. “My research has always been associated with potential application,” Zhang says. “The research projects I pick up for my own lab have always been related to patients or possible future applications.” And it was an interaction with a patient that would lead to his first momentous discovery and become the impetus for his career over the last two decades.
In 2001, Zhang published a paper on his lab’s generation of neuronal stem cells from human embryonic stem cells. Then got a phone call. When he picked up the call, he could barely understand the man speaking on the other line. “I could not hear his voice clearly,” says Zhang. It turns out that the man, who was calling from Texas, was on a ventilator which was garbling his voice. “He had ALS,” Zhang recalls. Amyotrophic lateral sclerosis (ALS), is a devastating and progressive neurodegenerative disease that causes the degeneration of motor neurons, a specific type of nerve cell in the brain and spinal cord, leading to eventual paralysis and death.
The Texan implored Zhang to focus his work more specifically on motor neurons. “I said I had never worked on motor neurons. He said you need to work on it. You need to do this,” Zhang says. But he decided to give it a shot. In 2001, Zhang became the first in the world to generate neurons from human embryonic stem cells. This ground-breaking discovery opened countless doors, including the path toward differentiating stem cells into all different kinds of neurons. By 2005, his lab succeeded in generating motor neurons from human stem cells, another first in the world.
Since then, he has generated many different types of neurons that are associated with several different neurodegenerative conditions. The theory was that if these human stem cell derived neurons could be transplanted into a patient to replace the faulty neurons driving a condition, that the patient could at the least have milder symptoms and at the most be cured of the disease. Once it was discovered how to produce induced pluripotent stem cells (iPSC) in 2006, Zhang moved away from embryonic cells. iPSCs are cells that are taken from an individual and forced back into a stem cell like state. From there they can be coaxed into a variety of different forms.
With this moonshot in mind, Zhang began looking at the possibility of developing stem cell therapies that could replace damaged or deteriorating neurons with healthy ones as a potential treatment for conditions like Parkinson’s and ALS.
The foundation of this stem cell treatment for Parkinson’s has proven possible in animal models. Zhang successfully transplanted healthy iPSC stem cell-derived dopaminergic neurons into the brains of mice and primates with Parkinson’s, with both species seeing remarkable improvement in symptoms. Studies led by Zhang have also continued to show that the new neurons integrate well into the brain and help to restore damaged circuitry.
This year, Zhang’s BrainXell moved closer to human clinical trials for the transplanted stem cell therapy. The studies in animal models have shown that the transplanted cells find their way in the brain and connect to the right targets. The cells were found to be safe and effective over a long period of time and showed consistent recovery of disease symptoms. The next step is to procure Food and Drug Administration (FDA) approval to begin a human clinical trial. Already in the midst of that process, Zhang is hopeful they will receive approval in the next several years.
“This is probably one of the most exciting events in my career because, out of medical school, I wanted my research to be related to clinical application,” Zhang says. “I told myself a long time ago that my goal is to at least try and get one thing to patients, ideally before I fully retire.”
This potential trial isn’t Zhang’s only exciting news in 2024. Earlier this year, Zhang and his lab became the first in the world to 3-D print functional brain tissue that is capable of growing and functioning like typical brain tissue. This advancement has the potential to revolutionize the field of neuroscience because of its ability to make studying brain functionality and development more easily accessible.
As Zhang wraps up his time at the Waisman Center, he will be sorely missed as not only an exceptional scientist but as a kind and compassionate person. The Waisman Center wishes Zhang all of the best in his future endeavors. His legacy and contributions to the field of neurodegenerative diseases will impact and inspire the researchers here for decades to come.
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