Assessment of safety and efficacy of human embryonic stem cell therapy
Study suggests hESCs could serve as a safe source of cells to treat diseases of the eye
Worcester,
MA June 11, 2009 (EurekAlert)--Advanced Cell Technology, Inc.
(OTC:ACTC.PK) and its collaborators at OHSU reported today the
long-term safety and efficacy of human embryonic stem cell
(hESC)-derived retinal pigment epithelium (RPE) produced under
manufacturing conditions suitable for human clinical trials. Two
important early potential hESC applications are the use of RPE for the
treatment of age-related macular degeneration and Stargardt disease, an
untreatable form of eye disease that leads to early-onset blindness.
The research, which appears online ahead of print in the journal Stem Cells,
shows long-term functional rescue using hESC-derived cells in both the
RCS rat and Elov14 mouse, animal models of retinal degeneration and
Stargardt, respectively. The cells survived transplantation for
prolonged periods (>220 days) and sustained visual function without
tumor formation or untoward pathological reactions. Near-normal
functional rescue was also achieved in the 'Stargardt' mouse. To
further address safety concerns, a study was carried out in the NIH III
immune deficient mouse model. Long-term data (spanning the life of the
animals) revealed no evidence of tumor formation after transplantation.
"We're delighted with these results," said Robert Lanza, Chief
Scientific Officer at ACT, and co-senior author of the study.
"Everything looks great so far. Based on these and other studies, we're
on schedule to file an IND with the FDA to begin human clinical trials
sometime in the next 3 or 4 months. Barring any surprises, Stargardt
disease and macular degeneration are likely to be the next two clinical
applications of ES technology.
Since their discovery over a
decade ago, hESCs have been considered a promising source of
replacement cells for clinical studies. However, problems continue to
plague clinical translation, including the risk of teratoma formation
and the need for powerful drugs to overcome the problem of immune
rejection. Until induced pluripotent stem (iPS) cell technology is
further developed, hESC-derived therapies are likely to be limited to
immunoprivileged sites such as the central nervous system and the eye.
In the retina, compromised RPE function can lead to deteriorated vision
and photoreceptor loss in both age-related macular degeneration and
other forms of degenerative eye disease. In this study, the cell
manufacturing and documentation process complied with the guidelines
set forth by the FDA, collectively referred to as Good Manufacturing
(GMP) and Good Tissue Practices.
The cells were prepared for
clinical application and tested for safety and efficacy in several
different in vitro and animal models in collaboration with researchers
at the Casey Eye Institute at Oregon Health and Science University
(OHSU) headed by Dr. Raymond Lund. Dr. Lund, co-senior author of the
paper, is widely considered one of the world's foremost experts in
retinal cell physiology and vision restoration. RPE from different hESC
lines were tested in the RCS rat, an animal in which vision
deteriorates over several months due to an RPE functional defect. The
studies focused on longevity of effect, dosing effect, and evidence of
untoward pathology. After three months, the treated retina had 5-6
layers of photoreceptors, whereas the untreated animals only had a
single layer of cells remaining (they were essentially blind). Based on
these data, a cell batch was chosen for a GLP safety study using the
NIH III mouse model, an immune deficient animal model. Importantly, we
also showed that vision can be rescued in a mouse model of Stargardt's
disease, which is a form of early-onset macular dystrophy that leads to
blindness despite an intact Bruch's membrane (critical for RPE cell
attachment and potential clinical efficacy).
"We have worked
with Dr. Lund and his team for over three years investigating the
safety and efficacy of our RPE cell therapy," stated William M.
Caldwell IV, Chairman and CEO of ACTC. "We are now completing the
finishing touches to seek FDA approval to conduct human clinical trials
with a cell therapy that may be able to address many of the 200 plus
known retinal diseases."
###
The
researchers of the paper from Advanced Cell Technology, collaborated
with scientists from Casey Eye Institute at the Oregon Health &
Science University, Portland, Oregon. The paper's other authors are Bin
Lu (co-equal first author), Shaomei Wang (co-equal first author),
Sergej Girman, and Peter Francis at OHSU; and Christopher Malcuit
(co-equal first author) and Linda Lemieux of ACT.
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