I copied this from tets post on yahoo thanks tet...
Making Headway Against Sickle-Cell
Causes Treatable for 1st Time
By Justin Gillis
Washington Post Staff Writer
Saturday, August 15, 1998; Page A01
Gregory McNair was draining motor oil at a Jiffy Lube in Jacksonville,
Fla., when he felt a familiar dull ache start in his ankles and creep up his
legs. His spirits fell. By the next day he was lying in a hospital bed, suffering
another bout of the excruciating pain that has defined his life.
This time, though, he signed some papers, and a mysterious fluid began
flowing into his veins. Within a couple of days he was feeling much better.
It was the fastest recovery from a pain attack he's ever had.
"Normally it would take two or three weeks to get better," he said. "With
the drug it takes three or four days, at least for me. I think it helps a lot."
McNair suffers from sickle-cell disease, a debilitating ailment that slowly
destroys the bodies of many of its victims, sometimes slicing 20 years or
more off their lives.
The treatment he received is one of several new drugs for the ailment. They
are not miracle cures, but they nevertheless herald a dramatic change. It
has taken science half a century to get this far, but the era has finally
dawned when the causes of sickle-cell disease can be treated. Victims can
now hope to claim back some of the years of life the disease steals from
them.
About 72,000 people in the United States suffer from sickle-cell disease.
Most are black. A few famous people, such as jazz trumpeter Miles Davis,
have suffered from the ailment, and black universities such as Howard
University have felt a special obligation to conduct research into it.
Over the years, some of the victims have wondered if treatments would
have been so slow to arrive had the patient population been mostly white.
Researchers say the relatively small number of patients tended to reduce
the funds devoted to sickle-cell studies. What is changing now, in part, is
rising interest among biotechnology companies in tackling what they see as
a neglected problem.
Biotechnology is still a small field, but research in it has exploded over the
past few years as companies use advancing knowledge of the body to find
new treatments for old afflictions. Sickle-cell disease is an inherited genetic
disorder, and finding treatments for it plays to the biotech industry's
strength in understanding the genetic components of disease. Down the
road, researchers hope that biotechnology might allow them to correct the
genetic trait that causes the illness.
Researchers also credit the National Institutes of Health in Bethesda with
decades of important work on sickle-cell disease. Earlier this year, in a
milestone, the Food and Drug Administration approved the use of a drug
called hydroxyurea that was tested partly at NIH. Taken every day as a
preventive, it lessens the frequency and severity of sickle-cell attacks in
many patients.
Ted Nicolas, a financial analyst from Columbia, heard about hydroxyurea
before it was approved. He was wary of being a guinea pig but weary of
checking himself into the hospital 20 or 25 times a year. He decided to try
it and enrolled in NIH studies that helped to prove the drug works.
The hydroxyurea pills are a boon, giving him more time to spend with his
wife and baby boy. "I've gone maybe five months, half a year without any
serious crises," he said. "It's a big change."
Soon there may be more choices for people like him. Biotech companies in
Georgia and California have entered advanced human testing with two
more drugs -- including the one McNair, the Jiffy Lube worker, has taken
-- that seem to help alleviate sickle-cell attacks once they start.
McNair was so thrilled the first time he got the drug last summer that he
asked for it again during his next pain attack in December, even though the
original study was over and the drug hadn't been approved for general use
yet. With special permission from the FDA, the company gave him the
drug, again with happy results.
Doctors at Harvard University are leading a study that uses a gas called
nitric oxide to try to alleviate acute attacks. They caution that their
evidence is sketchy -- the studies are still at an early stage -- but they have
seem some "dramatic" turnarounds in patients who were at death's door.
Early human studies have begun on other drugs, and yet more are being
scrutinized in the laboratory. Biotech firm MedImmune Inc. of
Gaithersburg is working on a vaccine that might prevent one of the worst
complications of sickle-cell disease.
With the new drugs has come a sharp change of mood among doctors
who treat the ailment. "For a long time there was nothing. It was dismal,"
said Kenneth R. Bridges, director of the sickle-cell center at Harvard's
Brigham and Women's Hospital. "I think we're entering a new frontier.
There's a lot of potential to help people."
Sickle-cell disease is a genetic affliction most common among people
whose ancestors lived in tropical countries. Perhaps 10 percent of black
Americans and a handful of white Americans carry a gene for the disease,
but most do not have the diease.
Having a single copy of the gene is an advantage in tropical countries: It
makes the carrier more resistant to malaria. But inheriting two copies, one
from each parent, gives a child sickle-cell disease. About 1 in 400 black
babies born in the United States has the ailment.
In many people the disease is mild, but in others it is agonizing, causing
lifelong pain and gradually destroying major organs.
People with the disease suffer a minute change in the structure of
hemoglobin, the component of blood that carries oxygen throughout the
body. Red blood cells, which contain hemoglobin, need to be flexible so
they can squeeze through tiny blood vessels. But in people with sickle-cell
disease the hemoglobin molecules often clump together into long chains,
deforming the cell into an elongated shape often compared to a half-moon
or a sickle.
These rigid, sickle-shaped cells tend to clog tiny blood vessels, interrupting
blood flow and starving nearby cells of oxygen and energy. During acute
attacks, the pain can be severe, and organs such as the kidneys or spleen
can suffer irreparable damage. Victims are prone to many complications,
including life-threatening infections.
Nicolas, the Columbia man, has lived with severe bouts of sickle-cell pain
for his entire life. "I'm in pain right now," he said in an interview at his
kitchen table. Tugging at his leg was Matteo, his cherubic son, too young at
19 months to understand his father's travails. (The baby has the sickle-cell
trait but not the disease.) Across the table sat Marie, his wife, a nurse who
decided long ago that Nicolas's ailment wouldn't stop her from marrying
him.
The pain cropped up when Nicolas was a boy, then got worse during
college. He is 28 now, and for years he had a hard time going a week or
two without a pain attack severe enough to send him to the hospital. Once,
he spent a month there when doctors discovered part of a leg bone had
died. "It scared the hell out of me," he said.
Through all this he finished college and built a career in finance -- he helps
a nursing-home company manage its bank accounts. He has a good
doctor, but for most of his life doctors haven't had much to offer except
pain killers.
But that has started to change. In 1995, learning of some promising new
work, Nicolas's doctor urged him to visit the NIH.
Scientists had long known that people with sickle-cell disease do better if,
through a genetic quirk, they retain high levels of the kind of hemoglobin
they had as newborn babies. This "fetal hemoglobin" is structurally different
from adult hemoglobin, but it seems to work perfectly well in grown-ups.
And unlike adult hemoglobin, it doesn't clump together and force cells into
a sickle shape.
In the mid-1980s, scientists at institutions such as NIH, Harvard and Johns
Hopkins University realized they might be able to use drugs to force the
body to produce high levels of fetal hemoglobin, even in people without a
genetic tendency to do so. They eventually settled on hydroxyurea, an old,
relatively mild cancer chemotherapy drug that appeared to have the
desired effect.
Griffin Rodgers, a top NIH researcher, led a pilot study that resulted in an
important paper in 1990 in the New England Journal of Medicine. This
study proved that hydroxyurea could indeed raise fetal hemoglobin levels in
some people.
A larger trial was mounted to discover whether the drug would actually
make patients better. This work culminated, in 1995, in a dramatic
announcement. The drug showed such a clear benefit that it became
unethical to continue withholding it from patients, and the test was stopped
early. The drug cut the number of sickle-cell attacks nearly in half and
lessened other complications. And its side effects seemed manageable.
Hydroxyurea was already on the market for other purposes, so a
nationwide alert advised doctors that at last, a treatment had been proven
to work.
Though it doesn't help as many as a quarter of those who take it, the drug
has revolutionized some people's lives. "Many of them are able to go back
to work," Rodgers said. "These patients clearly have a substantial
reduction in their number of crises."
Now, the news is coming fast. CytRx Corp. of Norcross, Ga., has
announced positive initial results with a treatment that it calls Flocor. The
treatment is a purified form of a soapy substance widely used in industry.
Given intravenously during sickle-cell attacks, the compound seems to
work as a lubricant, allowing blood with sickle-shaped cells to flow more
easily. There is some concern about possible kidney damage, but the
company has refined its drug to try to combat that problem. In March,
CytRx announced it would enroll patients in a large, definitive study of the
treatment.
A California company, Cypros Pharmaceutical Corp., has also entered
advanced human testing with a sickle-cell treatment, a sugary compound
that it calls Cordox. This substance may allow cells to survive longer even
when clogged blood vessels are starving them of oxygen and glucose. It
was this treatment that seemed to offer such striking benefits to Gregory
McNair, the Jiffy Lube worker in Jacksonville.
Other laboratories are looking at drugs that might be better than
hydroxyurea at raising fetal hemoglobin levels. And at Harvard and other
labs, work has begun on nitric oxide, a gas that might be given during acute
attacks to lessen the tendency of hemoglobin molecules to clump together.
Bone-marrow transplants, a radical treatment in which a patient's marrow
is destroyed and replaced to produce immune and blood cells, can cure
sickle-cell disease. But the risk of death from the treatment itself is fairly
high, and other problems also limit its usefulness. Some companies,
including MedImmune Inc. of Gaithersburg, are looking for ways to cut the
risk.
Finally, some scientists are trying to correct the genetic anomaly that leads
to sickle-cell disease. The prevailing view is that this strategy will take a
while to pay off, but if it ever does, it could cure the ailment with little risk.
For people like Nicolas, that day can't arrive too soon.
His battle with the ailment has been so dreadful, he said, that many people
in his family did not think he would be alive in 1998. He is doing better
than he has in years, but as he tussles with his son, he wonders aloud what
the future holds. The statistics about shortened life expectancy unnerve
him.
"This is me they're talking about," he said. "With each crisis, I'm losing a
part of my body. How much do I have left?"
FOR MORE INFORMATION
People wanting more information about experimental treatments for
sickle-cell disease can contact the following sources.
For studies at the National Institutes of Health in Bethesda, phone
301-496-4891 or 1-800-411-1222 or send e-mail to prrc@cc.nih.gov.
For information about other studies around the country, call the National
Heart, Lung and Blood Institute at 301-435-0055.
For information about the advanced human tests of the drug Flocor by
CytRx Corp. of Norcross, Ga., call the company at 770-368-9500. For
information about the advanced tests of Cordox by Cypros Pharmaceutical
Corp. of Carlsbad, Calif., call the company at 1-888-297-7671.
c Copyright 1998 The Washington Post Company |
