An Experiment That Blinded Three Women Unearths The Murky World Of Stem Cell Clinics


The story began, like so many in biotechnology, with an
upbeat
press release: Up to 100 patients with a progressive form
of blindness would be treated with cells extracted from their
own body fat, in a clinical research trial.

“We are excited to determine whether cellular therapy can offer
new hope to this patient population,” the lead researcher on
the trial, Shareen
Greenbaum of the Hollywood Eye Institute in Cooper City,
Florida, said in the release.

The trial also seemed to have an impressive ethical stamp of
approval. “The study has been reviewed and approved by the
Institutional Review Board (IRB) of the International Cellular
Medicine Society (ICMS),” the press release, issued in December
2013, noted.

But by June 2015, the story had turned into a tragedy. As
BuzzFeed News
reported last week, three elderly women whose eyesight was
still reasonably good became legally blind after cells from
their body fat were injected into their eyeballs. One, a
retired college professor from Missouri called Elizabeth Noble,
can no longer tell night from day.

The Florida company behind the study, formerly known as

Bioheart and now called US Stem Cell, now
denies that the trial ever started. But a 2016
court filing in a suit brought by another of the women who
was blinded, a Florida retiree called Patsy Bade, suggests
otherwise.

The ethical review board, meanwhile, has distanced itself from
the trial,
saying that it only approved plans to treat patients who
were already legally blind — and then only in one eye at a
time.

Inquiries by BuzzFeed News reveal that the original ethical
approval raised troubling questions from the start. The ICMS
lobbies for doctors’ right to practice stem cell medicine free
from federal oversight. “No other group has done more to
protect a physician’s right to practice stem cell and
regenerative medicine,” its website
claims. ICMS council members and advisers must
affirm that stem cells are “exempt from any US Food and
Drug Administration regulations” — as long as the cells are
injected back into the same patient they came from, and have
not been grown in laboratory cultures.

What’s more, the ICMS ethical board that approved the trial
included one doctor whose medical license had been
placed on probation for failing to meet the “applicable
standard of care” in his own medical practice, plus another who
had earlier been
convicted of violating federal law by breaching a patient’s
medical privacy.

Those doctors refused to comment on the trial’s approval and
their own qualifications to serve as ethical reviewers. After
inquiries from BuzzFeed News, the ICMS
posted a statement on its website, stating that did not
approve the specific treatment that led to the three women
losing their sight. But its executive director, Reed Davis,
refused to answer questions.

“The statement posted on the ICMS website is the extent of our
comment on this matter,” Davis told BuzzFeed News by email.
“Furthermore, I am respectfully requesting that you cease
contacting and harassing members of the IRB.”

The FDA maintains that stem cells should be treated as
experimental drugs, requiring extensive scientific testing
before they can be approved for regular clinical use, if they
have been subjected to anything more than “minimal
manipulation.” In
draft guidance published in December 2014, the agency
suggested that cells extracted from a patient’s own body fat,
like those used to treat the three women who were blinded in
Florida, would fall into the more-than-minimally-manipulated
category.

But for years, rebel doctors have fought against the FDA’s
authority. The battle lines were drawn in 2008, after the FDA
told
a Colorado doctor called Christopher Centeno to stop marketing
a stem cell therapy called Regenexx, used to treat arthritis
and joint injuries. It took until 2012 before the agency
prevailed, when a federal court
ruled that the treatment was a drug, requiring FDA
approval.

The ICMS was forged in the heat of that legal dispute. Centeno
was also the
medical director of a nonprofit called the Spinal Injury
Foundation, which by 2010 had been
reconstituted as the ICMS. It lobbied for stem cell
therapies to be treated as the “practice of medicine,” rather
than drugs, and established an
Institutional Review Board to approve clinical studies.

But the ICMS IRB
was chastised by the FDA in June 2012 for approving a stem
cell clinical trial that the agency had shut down three years
before. That letter documented a series of problems with the
IRB’s procedures, including granting approval without the
required quorum of members being present.

View this image ›

The retina of a patient with
macular degeneration, in which fatty deposits (center
right) form in the region used for detailed vision.
National
Eye Institute, NIH

ID: 10742613

In late 2013, the ICMS IRB reviewed the Florida trial, intended
to test the ability of stem cells from fat to treat an eye
disease called Age-Related
Macular Degeneration, which slowly robs people of the sharp
central vision they rely on to read and drive. By then, Centeno
had parted ways with the organization. “I have not been
involved with the ICMS in many years and have no part in the
approval of this protocol, nor would I have approved it had I
been part of the organization,” he told BuzzFeed News by email.

The ICMS IRB
that reviewed the Florida clinical trial consisted mostly
of doctors who themselves practice unproven stem cell
therapies. Its chair was David Harshfield, who works at the
Arkansas Institute of Regenerative Medicine in Little Rock, and
who has trained other doctors to set up their own stem cell
practices. A 2015
press release about a workshop in Puerto Rico says that he
would “teach doctors how to use and successfully market” stem
cell therapies.

Harshfield did not respond to phone calls and emails from
BuzzFeed News.

The IRB also included another Arkansas doctor, Jay Holland, who
in 2009
pled guilty to violating federal law on medical privacy.
Then at the St. Vincent Infirmary Medical Center in Little
Rock, Holland watched a report about a local TV news reporter
who had been found beaten and bloody in her bed. (She later
died from her injuries.) Filled with curiosity, Holland
illegally accessed the reporter’s medical records from his home
computer. He was
sentenced to one year’s probation, and fined $5,000.

In a promotional video, Jay
Holland describes using blood plasma, stem cells, and lasers
to treat chronic wounds. His collaborator, Carl Keller, is a
“community member” of the ICMS IRB. youtube.com

ID: 10742040

Another member of the ICMS IRB was Dean Reeves, a doctor in
Roeland Park, Kansas. In April 2012, his medical license was

put on probation by the Kansas State Board of Healing Arts,
which regulates doctors in the state, because of problems with
his use of “prolotherapy” — an alternative medical practice in
which doctors inject patients’ joints with fluid, which is
supposed to promote healing. The board faulted him for issues
including failing to properly use medical imaging to guide his
injections, failing to combine the treatment with physical
therapy, and failing to document important aspects of the
procedures, including his use of sedation.

Both Holland and Reeves hung up when BuzzFeed News asked them
about their troubled disciplinary histories. “We won’t continue
this conversation. We need to say goodbye,” said Reeves — whose
disciplinary difficulties continue to this day. In September
2016, Reeves
wrote to the Kansas board, requesting that his probation be
terminated. But in November, the board
initiated fresh proceedings against him, alleging further
departures from appropriate care in Reeve’s treatment of 15
patients.

“It’s very easy to find physicians who do not have a troubled
disciplinary history,” Leigh Turner, a bioethicist at the
University of Minnesota who last year
published a survey of clinics offering unproven stem-cell
therapies, told BuzzFeed News. “These are individuals that
undercut the integrity and credibility of the IRB.”

Turner also argued that the ICMS has “obvious conflicts of
interest” when acting as an independent ethical reviewer for
stem-cell studies that have not been submitted to the FDA for
approval, given its opposition to the agency’s regulatory role.

The ICMS and Kristin Comella, chief science officer for US Stem
Cell, once had a professional relationship. In 2012, before her
company submitted the macular degeneration trial for approval
to the society’s IRB, she was a prominent speaker and one of
the “conference
faculty” at a scientific
meeting in Florida organized by the ICMS.

Today, things are rather different. Comella and Becker Public
Relations, which represents US Stem Cell, did not respond to
emails and phone calls from BuzzFeed News. But last week,
Comella
told the New York Times that an independent review
board approved the plan to treat patients in both eyes at once.

That was flatly contradicted by the statement posted online by
the ICMS, which stated: “Throughout the protocol, the treated
eye is consistently referred to in the singular and the
protocol does not contemplate, much less condone, bilateral
treatment. If the protocol had mentioned bilateral treatments,
it would not have received approval from the ICMS IRB.”

On one point, however, the ICMS and US Stem Cell are still on
the same page: The trial, they both claim, never enrolled any
patients.

Yet in repeated filings to the Securities and Exchange
Commission, most recently in its
annual report for the year ending December 31, 2015 — more
than two years after the original press release announcing the
clinical trial — US Stem Cell wrote: “We have also initiated
several Institutional Review Board studies in 2013 using
adipose derived stem cells for various indications including
dry macular degeneration.”

A July 2016
court filing by Patsy Bade, after she had settled with US
Stem Cell but before her settlement with Greenbaum, alleges
that the trial did start enrolling patients. It indicates that
Greenbaum was convinced by Comella — they met at the gym where
Comella was an aerobics instructor, according to the court
document — to become the trial’s lead researcher. Greenbaum was
allegedly trained by Comella in how to harvest and use stem
cells from fat, with the $7,500 cost being deferred in exchange
for Greenbaum agreeing to work on the clinical trial.

The court filing indicates that Greenbaum treated “approximately
six” patients as part of the clinical trial, before she
started to have misgivings about its legitimacy.

In Spring 2015, according to the court filing, Greenbaum told
Comella that she could no longer participate. But she allegedly
still conducted an initial examination of the three women who
were subsequently blinded, before Comella and a registered
nurse conducted the procedure.

Greenbaum has since settled with Bade, in an agreement that
prevents all of the parties from discussing the case. She did
not respond to calls and emails from BuzzFeed News.

Whether or not the trial actually enrolled any patients, Turner
argues that there is a serious problem.

“The company seems to have made the determination that this was
clinical research,” he said. “Why were the patients being
treated if they weren’t being giving cells as part of study?”



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