Researchers at the University of Pennsylvania School of Medicine performed the first postmortem examination of a brain implanted with cloned human neurons to treat damage due to stroke.
They hoped that the grafted neurons would re-establish brain circuitry damaged by stroke in order to restore lost motor and cognitive function.
Their findings, presented in the April issue of the American Journal of Pathology, give further evidence that adult human neurons, cloned and grown in culture, can make a safe and effective therapy to reverse the neurological effects of stroke.
"Our findings show that these implanted neurons survived for more than two years without causing any harm to the patient whatsoever," said John Q. Trojanowski, MD, PhD, professor in the department of Pathology and Laboratory Medicine and co-director of Penn's Center for Neurodegenerative Disease Research (CNDR).
In the Phase I clinical trial, six of the twelve participants showed marked improvements after implant surgery. The patient in this study, however, did not show improvement.
The patient, a 71-year-old man, died from a heart attack 27 months after implant. The grafted cells were human NT2N neurons (hNT) developed by Trojanowski and his colleagues at Penn from the well-studied Ntera2 (NT2) teratocarcinoma cell line.
"Since these cells were cloned and grown in culture, there is a concern that they may continue to reproduce like cancer cells," said lead author Peter Nelson, MD, a Penn neuropathology fellow. "However, none of the cells near the implantation site appeared cancerous."
Stroke affects more than half a million people in the United States each year and, while less than a third of strokes are fatal, about 60% of victims are affected by a decline in muscle control and cognitive function. As yet, there is no proven therapy for treating lasting damage from stroke.
"As the population ages, strokes and neurodegenerative diseases, such as Alzheimer's and Parkinson's, will become more prevalent," said Trojanowski. "Grafted hNT cells show remarkable promise in their ability to restore stroke damage."
Unlike cells derived from embryonic stem cells, the use of cloned adult cells does not pose any ethical or legal problems. In addition, they do not harbor known human pathogens or potentially infectious agents as might be found in transplants from other species.
The safety of hNT cells is well documented and has been used previously in normal rodents as well as animal models of stroke, Huntington's disease, Parkinson's Disease and trauma, with encouraging results. The cells have been extensively characterized in vitro, and are amenable to genetic engineering.
"What is potentially most important is that NT2 neurons can be grown in unlimited quantities," said Trojanowski. "These cells represent a relatively inexpensive and limitless source for therapy."
The Phase I clinical trial was conducted at the University of Pittsburgh Medical Center. The trial leaders there sent the brain to Penn's CNDR for study and comparison to other brains in their extensive brain bank.
Trojanowski's group was unable to find a tumor anywhere in the brain and, furthermore, the researchers were unable to find evidence of complications due to implant surgery.
The clinical use of hNT cells is currently undergoing a Phase II trial at the University of Pittsburgh Medical Center.
This study, and the clinical trial, was supported by Layton Bioscience, Inc. Trojanowski and Virginia M.-Y. Lee, PhD, are the founders of -- and consultants for -- Layton Bioscience, and hold equity in the company. The University of Pennsylvania is also a part owner of the company.
[Contact: Greg Lester]