Monday October 06, 2014
A Small Number of Patients With Fetal-Cell Transplants Are
Thriving Two Decades Later
Shirley S. Wang
Wall Street Journal - Several patients with Parkinson’s
disease who received brain-tissue transplants from fetuses in the early 1990s
have needed little or no medicine to treat the disease ever since—an outcome
virtually unheard of in the course of the disease, researchers have found.
The
results are particularly striking because the treatment is controversial and
has been questioned by some researchers in the field.
Bolstered
by these promising cases, 14 European hospitals, research institutions and
companies have launched a new, controversial trial on fetal-cell transplants,
known as Transeuro. Funded with a $15 million grant by the European Union,
surgeons in Cambridge, England, are expected to perform their first transplant
on a trial participant by year’s end. It would be the first since the 1990s.
WHERE FETAL CELLS MIGHT HELP
A
fetal-cell transplant is an experimental technique in which healthy cells from
fetuses are implanted into people with disease. The treatment has been
considered for potential use in the following conditions:
• Parkinson’s
disease
• Alzheimer’s
disease
• Huntington’s
disease
• Multiple
sclerosis
The
debate primarily stems from two U.S. government-funded clinical trials that
found such transplants didn’t significantly benefit the overall group of
participants. There are also risks: Some patients developed involuntary
movements that could be severe.
But
some European researchers have challenged aspects of the U.S. trials for years.
They argue that the scientific community prematurely dismissed the idea of
fetal-cell transplants for Parkinson’s. The disease is a condition in which
certain brain cells are damaged and die off, causing movement problems, tremors
and other symptoms. It affects 6.3 million people world-wide, according to the
European Parkinson's Disease Association.
The
use of human fetuses in research has been a hotly debated topic, with
moratoriums issued in the U.S. for federal funding of fetal tissue and
stem-cell research at times over the past 40 years. Critics suggest that a
demand for fetal tissue might encourage abortion. The U.S. federal government
is now allowed to fund embryonic stem-cell research.
The
idea of replenishing damaged cells with fresh, healthy ones to treat or even
cure disease has been a scientific dream. But progress has been slow. The
Transeuro trial will test whether cell therapy—in this case transplanted
dopamine cells—may help Parkinson’s patients above and beyond current
medications and brain-stimulation techniques.
In
the trial, doctors take brain cells that make dopamine, a neurotransmitter depleted
in Parkinson’s, and implant them into different areas of an adult brain through
a small hole in the skull. The goal is for the cells to grow normally. The
brain tissue—an amount smaller than the size of a walnut—is taken from fetuses
that were aborted and would be otherwise discarded.
Scientists
hope that as cell-therapy science continues to advance, the treatment will
shift to using stem cells rather than fetal tissue. Stem cells provide a
renewable source of cells and are more versatile, able to differentiate into
any type of cell. Some types can exist in adults, but they need to be coaxed or
programmed into nerve cells that produce dopamine.
If
the Transeuro trial shows that patients gain improvements after the transplant
with reduced side effects, “there’s a future for stem cells” with the disease,
says Stanley Fahn, a neurology professor at Columbia University in New York who
was the co-primary investigator on one of the two National Institutes of
Health-funded transplant trials in the 1990s.
The
current mainstay of treatment is a medication called levodopa, which boosts
dopamine in the brain. Long-term, however, levodopa use tends to induce
uncontrollable involuntary movements known as L-dopa-induced dyskinesia. It
also only tends to work for part of the day.
Deep-brain
stimulation, or DBS, which sends a small amount of electric current into a
strategic nerve center that controls movement, appears to be a better option.
Not all people, however, can or want to undergo DBS, and its effects can be modest.
Some
experts have serious concerns about how useful the Transeuro results will be
because it lacks a control group, which is typically a requirement in a
high-quality clinical trial. That means participants and the researchers could
be affected by bias, perhaps unconsciously, says C. Warren Olanow, a
neuroscience professor at New York’s Icahn School of Medicine at Mount Sinai
who led the other U.S. trial.
In
addition, Parkinson’s research in the last decade or more has found that other
cells, not just dopamine neurons, are involved in the disease. The transplant
presumably wouldn’t improve symptoms caused by those other cells.
University
of Cambridge neuroscience professor Roger Barker is coordinator of
Transeuro. UNIVERSITY OF CAMBRIDGE
Roger
Barker, the coordinator of Transeuro and a clinical neuroscience professor at
University of Cambridge , acknowledges the concerns. Instead of having a
control group, all participants will be matched with patients of similar disease
severity and age and videotaped while wearing caps to hide any signs of the
cell transplants. The videos will be assessed for changes in symptoms and
behavior by independent raters who won’t know who received the transplant.
The
transplant would likely only benefit a subset of people with Parkinson’s and
wouldn’t necessarily improve all the symptoms associated with the disease, Dr.
Barker says. He adds that the coming transplants will improve on the previous
ones by implanting more dopamine cells relative to other types of cells,
hopefully reducing side effects. This study also involves younger patients with
less advanced disease who are likely to respond.
Doctors
must use great caution with cell therapy. Once fetal tissue cells are
implanted, they can’t be controlled or easily removed. In the past, some
patients experienced involuntary movements that developed from the transplant,
known as graft-induced dyskinesia. Further treatment can make it more mild but
it can’t be easily reversed, and there are other potential secondary risks.
In
the two U.S. trials, which consisted of 34 and 40 patients each, brain scans
showed that the transplanted dopamine cells did survive. But it wasn’t clear
whether the cells integrated into the brain circuits normally, Dr. Olanow says.
The
transplant didn’t have any substantial effect in any patients over age 60, Dr.
Fahn says of his study with Curt Freed, a medicine professor at the University
of Colorado, Denver. In contrast, several of the younger cases did benefit and
were able to come off or reduce their medication eventually.
Dr.
Fahn still sees one participant in his clinical practice who continues to do
well while taking a lowered dose of the medication, he says. The patient
declined to comment.
Thomas
Foltynie, a neurologist at University College London, also cares for two
patients who received transplants as part of an 18-person trial in Sweden in
the mid-1990s when they were at a moderate stage of disease and in their 40s.
He and colleagues published a case report on them in January in the
journal JAMA Neurology.
Before
their transplants, both patients still responded to levodopa for periods and
could function more or less normally when the drug was “on”. But during the
“off” periods, they were disabled, experiencing tremors, slowness and even
freezing in place, Dr. Foltynie says.
They
responded so well to the transplants that months afterward, doctors took them
off the drug. Both patients experienced the side effect of graft-induced
dyskinesia, Dr. Foltynie says. (Researchers determined the side effects were
due to the transplant, not the drugs.)
Now
15 and 18 years post-transplantation, both patients have non-motor symptoms of
the disease, like cognitive impairment. Recently one was diagnosed with cancer,
though Dr. Foltynie says this was thought to be unrelated to the transplant and
Parkinson’s. Both declined to speak for health reasons, according to Dr.
Foltynie.
There
are many unanswered questions about cell therapy but for these two patients,
“it’s hard to ignore the longevity of the benefit of the transplant,” Dr.
Foltynie says.
http://online.wsj.com/articles/second-thoughts-on-out-of-favor-parkinsons-disease-treatment-1412615382
