NY Times
Jan 23, 2008


                       F.D.A. Approves a Stem Cell Trial



   By [8]ANDREW POLLACK



   In a research milestone, the federal government will allow the 
world's

   first test in people of a therapy derived from human embryonic 
[9]stem

   cells.



   Federal drug regulators said that political considerations had 
no role

   in the decision. Nevertheless, the move coincided with the

   [10]inauguration of [11]President Obama, who has pledged to 
remove some

   of the financing restrictions placed on the field by President

   [12]George W. Bush.



   The clearance of the clinical trial -- of a treatment for 
[13]spinal

   cord injury -- is to be announced Friday by Geron, the 
biotechnology

   company that first applied to the [14]Food and Drug 
Administration to

   conduct the trial last March. The F.D.A. had first said no, 
asking for

   more data.



   Thomas B. Okarma, Geron's chief executive, said Thursday that 
he did

   not think that the Bush administration's objections to 
embryonic stem

   cell research played a role in the F.D.A.'s delaying approval.



   "We really have no evidence," Dr. Okarma said, "that there was 
any

   political overhang."



   But others said they suspected it was more than a coincidence 
that

   approval was granted right after the new administration took 
office.



   "I think this approval is directly tied to the change in

   administration," said Robert N. Klein, the chairman of 
California's $3

   billion stem cell research program. He said he thought the 
Bush

   administration had pressured the F.D.A. to delay the trial.



   Mr. Klein called the approval of the first human trial of this 
sort "an

   extraordinary benchmark."



   Stem cells derived from adults and fetuses are already being 
used in

   some clinical trials, but they generally have less versatility 
than

   embryonic stem cells in terms of what tissue types they can 
form.



   The F.D.A. approval comes a little more than 10 years after 
the first

   human embryonic stem cells were isolated at the [15]University 
of

   Wisconsin, in work financed by Geron.



   Because the cells can turn into any type of cell in the body, 
the

   theory is they may one day be able to provide tissues to 
replace

   worn-out organs or nonfunctioning cells to treat [16]diabetes, 
heart

   attacks and other diseases. The field is known as regenerative

   medicine.



   The Bush administration restricted federal financing for 
research on

   embryonic stem cells because creation of the cells entails the

   destruction of human embryos.



   Geron's trial will involve 8 to 10 people with severe spinal 
cord

   injuries. The cells will be injected into the spinal cord at 
the injury

   site 7 to 14 days after the injury occurs, because there is 
evidence

   the therapy will not work for much older injuries.



   The study is a so-called Phase I trial, aimed mainly at 
testing the

   safety of the therapy. There would still be years of testing 
and many

   hurdles to overcome before the treatment would become 
routinely

   available to patients.



   Geron, which is based in Menlo Park, Calif., said that it had

   identified up to seven medical centers for the trial but that 
those

   sites must first get permission from their own internal review 
boards

   to participate.



   Even as some researchers hailed the onset of clinical trials, 
others

   expressed trepidation that if the therapy proves unsafe -- or 
even if

   it is safe but does not work -- it could cause a backlash that 
would

   set the field back for years.



   "It would be a disaster, a nightmare, if we ran into these 
kinds of

   problems in this very first trial," said Dr. John A. Kessler, 
the

   chairman of neurology and director of the stem cell institute 
at

   [17]Northwestern University.



   Dr. Kessler, whose own daughter was paralyzed from the waist 
down in a

   skiing accident, said he thought Geron's therapy was not the 
ideal

   candidate for the first trial. He said results showing the 
therapy

   worked in moderately injured animals might not apply to more 
seriously

   injured people.



   "We really want the best trial to be done for this first 
trial, and

   this might not be it," he said.



   Dr. Okarma of Geron emphasized that the purpose of the first 
trial was

   safety, so that lack of efficacy should not be a problem. 
While

   researchers will also look for signs the treatment works, he 
said, the

   best that could be hoped for would be some slight restoration 
of

   function that could then be enhanced through [18]physical 
therapy.



   "We don't expect to take someone who is completely paralyzed 
from the

   waist down and have them dance six months later," he said. If 
the first

   trial shows safety, the company would then hope to test higher 
doses of

   cells and treat patients with less severe injuries, he said.



   Geron's therapy involves using various growth factors to turn 
embryonic

   stem cells into precursors of neural support cells called

   oligodendrocytes, which are then injected into the spinal cord 
at the

   site of the injury.



   The hope is that the injected cells will help repair the 
insulation,

   known as myelin, around nerve cells, restoring the ability of 
some

   nerve cells to carry signals. There is also some hope that 
growth

   factors produced by the injected cells will spur damaged nerve 
cells to

   regenerate.



   The therapy was developed in collaboration with Hans Keirstead 
of the

   University of California, Irvine. He has shown videos of 
paralyzed rats

   that were able to walk again, albeit imperfectly, after 
receiving the

   therapy. Those videos helped persuade California voters to 
approve the

   $3 billion stem cell research program in 2004.



   The main safety concern is that if raw embryonic cells are put 
into the

   body, they can form [19]tumors. Even though most such tumors 
do not

   spread like other cancers, any unwanted growth in the spinal 
cord can

   further damage nerves.



   "It's not ready for prime time, at least not in my mind, until 
we can

   be assured that the transplanted stem cells have completely 
lost the

   capacity for tumorogenicity," said Dr. Steven Goldman, 
chairman of

   neurology at the [20]University of Rochester. He was a member 
a

   committee convened by the F.D.A. last April to examine the 
safety

   aspects of trials using therapies from embryonic stem cells.



   Dr. Okarma said Geron had done numerous studies showing that 
its cells

   did not contain residual embryonic cells and did not form 
tumors in

   animals even after a year. It submitted 22,000 pages of data 
to the

   F.D.A., perhaps the largest application ever for permission to 
begin a

   clinical trial.



   The embryonic stem cell line used by Geron is one of the 
oldest ones

   and was therefore eligible for federal financing under the 
Bush

   administration's policy, Dr. Okarma said.



   Nevertheless, Geron paid for its own work, spending $45 
million to

   prepare its F.D.A. application.



   Geron, which was formed in 1990 as an antiaging company, is 
still in

   the development stage and is not yet profitable, having lost 
about $500

   million since its inception. Besides working on stem cells, it 
is

   testing drugs for [21]cancer that influence telomeres, the 
caps on the

   ends of chromosomes that help control the aging of cells. 
Geron's

   market value is about $400 million.



   While the Bush administration's policy did not impede the 
company's

   application at the F.D.A., Dr. Okarma said, it did slow 
progress for

   the field in general by making it hard for academics to do 
research.



   "It is the private sector that has kept the technology alive 
so that it

   can see the light of day in a clinical trial," he said.



   Mr. Klein of the California stem cell program said he thought 
the next

   trial might be of a treatment for [22]macular degeneration, an 
eye

   disease, that is being developed in Britain.



   In the last couple of years, some attention has turned away 
from

   embryonic stem cells to a newer technique that allows a 
patient's own

   skin cells to be turned into a cell resembling such embryonic 
cells.



   That might do away with the need for embryos. And the 
resulting tissue

   made from those cells would match the patient, doing away with 
the need

   for immune suppression to prevent rejection of the transplant. 
Geron

   said its trial would require only temporary use of low doses 
of

   immune-suppressing drugs.



   But the newer technique involves putting genes into the skin 
cells

   using viruses, which also raises a risk of cancer.

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