PA) - It appears that a little foreign culture is safe
for the mind, particularly if it is a culture of cloned
neurons. 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. It is hoped that the
grafted neurons will 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
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 of a million in the United
States each year and, while less than a third 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
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.
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