Happy New Year to all!!
I thought you might be interested in this article (see email below) about a
low-level chelation trial on children.
Yours Sincerely
Elizabeth O'Brien, Manager, Global Lead Advice & Support Service (GLASS) run
by The LEAD Group Inc.
PO Box 161 Summer Hill NSW 2130 Australia
Ph +61 2 9716 0132
www.lead.org.au


----- Original Message -----
From: <upal@...>
To: <leadnet@...>
Sent: Friday, January 04, 2008 8:50 AM
Subject: [Leadnet] Re: Wall Street Journal Article


This message was also sent by upal@... to: rscott@...

Happy 2008 everyone! The battle continues . . . . .

Pursuing a Cure For an 'Orphan' Ailment --- A Doctor Struggles to Develop A
Drug for Lead Poisoning; Bypassed by Patient Advocates By Amy Dockser
Marcus2092 words18 December 2007The Wall Street JournalD1English(Copyright
(c)
2007, Dow Jones & Company, Inc.)
For more than 20 years, Michael Shannon has used a drug called
d-penicillamine
to treat children with lead poisoning. The problem is that children often
won't take the drug because "it tastes and smells like rotten eggs," says
the
pediatrician at Children's Hospital Boston.
That's why he was thrilled when a company he collaborated with, Tedor Pharma
Inc., came up with a kid-friendly grape-flavored formula. He figured
pharmaceutical companies would be eager to license it and launch a trial to
obtain Food and Drug Administration approval, and parents would embrace it.
He
even expected the FDA to help out, and applied for a grant to help defray
the
costs of a trial.
Instead, "no one was interested," says Jacqueline Armstrong, project leader
in
the hospital's intellectual-property office, which guides development of
drug
discoveries.
Drug companies said the costs were too high to commercialize a drug for a
condition that affects relatively few children. Doctors were divided on the
use of drugs to treat the moderate levels of lead poisoning Dr. Shannon
targets; there was no proof that treatment could reverse cognitive damage.
And
Dr. Shannon says that the FDA, in its rejection of his grant request, said
it
wanted him to focus on higher levels of lead poisoning.
Most surprising was that no patient advocates took up the cause. Parents of
lead-poisoned children were leery of using drugs to treat lead poisoning --
a
process known as chelation that carries side effects of its own. In a
population that is disproportionately poor, urban and minority, many patient
advocates instead prefer to focus on cleaning up homes with high levels of
lead paint, the chief source of lead poisoning.
"I don't believe it is possible to reverse the damage from lead poisoning,
so
I don't want to take the risks of giving my son a medical intervention that
might cause other damage," says Zakia Shabazz, who founded a parent-advocacy
group, United Parents Against Lead National, in 1996 after her son, Zaki,
was
diagnosed with lead poisoning.
Patient-advocacy groups are increasingly powerful. They are raising huge
sums
of money for research, particularly for rare diseases that might otherwise
be
overlooked. Impassioned patients have recently funded their own trials,
hired
scientists and successfully lobbied government agencies. But as Dr. Shannon
discovered, some rare diseases are true orphans, unable to attract
drug-company, philanthropic or even patient-advocate interest.
Dr. Shannon's efforts might have remained stalled if not for a Boston-based
venture capitalist named Roger Kitterman. His suggestion for how to
jump-start
the project -- selling the idea to a group of investors willing to accept
smaller profits in order to fill a critical need -- brought in the vital
initial investment.
Dr. Shannon's push for a clinical trial came at a time that seemed
promising.
Massive recalls this year of millions of toys because of lead paint drew
attention to the serious health hazards posed by lead, which include brain
and
organ damage, learning disabilities and antisocial behavior. Though
lead-based
paint was banned in 1978, the Centers for Disease Control and Prevention
estimate that at least 24 million older housing units in the U.S. pose a
potential threat because of lead paint.
But lead poisoning -- how to treat it, prevent it, even define it -- is a
divisive issue. The CDC says a level of 10 micrograms or more of lead per
deciliter of blood in a child's body is cause for concern. But Dr. Shannon
and
other pediatricians argue that blood-lead concentrations below 10 mg/dl also
cause cognitive damage, and they have urged the CDC to lower the level even
further.
The latter view was supported in a recent study published in the New England
Journal of Medicine. In the study, researchers found that "there is no
evidence of any safe threshold for lead," said Richard L. Canfield of
Cornell
University, one of the investigators.
At the same time, there is little evidence that treating low blood levels of
lead poisoning makes a difference. The only FDA-approved drug for lead
poisoned children, called Chemet, has proved effective only in preventing
life-threatening complications such as seizures in children with very high
blood levels of lead, over 45 mg/dl. Some doctors will still treat levels
under 45, but at that point, the risks of chelating drugs -- which can cause
fevers, rashes, and drops in platelets and white blood cell counts -- are
seen
by many as outweighing the potential benefits. At lower levels of lead
poisoning, these doctors argue, it may be preferable to let levels fall
naturally over time.
To address lower-level poisoning, Dr. Shannon needed something else. Enter
d-penicillamine, a drug for rheumatoid arthritis and adults with a rare
genetic disorder. Dr. Shannon says years of off-label use of the drug in
thousands of children show that it significantly lowers patients' blood-lead
levels and keeps them down even after the drug was stopped. And while
d-penicillamine has potentially serious side effects at adult doses, at the
low doses given to the children, he says, there were milder reported events,
such as rashes and stomach upset.
Though there isn't enough research yet to show that cognitive damage from
lead
poisoning can be reversed, Dr. Shannon and some other doctors argue that
treatment can halt or reverse other serious damage done to organs. "Lead
affects every organ," he says. "The brain is the most important, but we also
have to think about the kidney, liver and bone marrow. The benefits there of
removing the lead are incontrovertible." So he and the hospital were eager
to
work with Tedor to develop a new, better-tasting formula for d-penicillamine
that could be FDA approved for kids and thus gain wider use.
In the months following the setbacks for the new version, Children's
Hospital
brought in business advisers to find a way to get the reformulated drug into
trial. Soon after, Mr. Kitterman, the Boston-based venture capitalist,
pitched
his idea: Eschew philanthropists and patient advocacy groups and focus on
finding investors who want to help the kids and are willing to accept a more
modest profit than they might typically expect. If costs stayed under $2
million, Mr. Kitterman calculated, the early investors could eventually make
at least two to three times what they put in.
With the hospital's OK, Mr. Kitterman formed Bezoloven -- the Bulgarian word
for "lead-free" -- a company with no office, no employees and very little
overhead. By fall 2006, he had raised $100,000 from a group of investors
called Boston Harbor Angels. While small, that initial funding enabled Dr.
Shannon to begin planning a full clinical trial.
The idea was to enroll 50 children over the course of three years,
randomized
into a group that would receive the drug and a group that would receive a
placebo, and see if it was effective in lowering lead levels.
If Bezoloven proves successful, the model could be used to support research
in
other rare diseases, says Donald P. Lombardi, CEO of the Institute for
Pediatric Innovation in Cambridge, Mass., which launched a consortium of
pediatric hospitals to identify and develop promising pediatric therapies.
He
says he knows of at least a dozen compounds that, like d-penicillamine,
could
be reformulated for FDA approval for pediatric use with investments of $2
million to $8 million. "This is the proof of a very important principle,"
Mr.
Lombardi says.
For now, the debate over when to use drugs to treat lead poisoning remains
unresolved. Treatment with chelating drugs is widely understood to be
necessary in cases where high levels of lead threaten the child's life. But
in
a seminal 2002 study of 741 toddlers with moderate lead poisoning (under 45
mg/dl), Chemet didn't significantly reduce lead levels. And after following
the children through ages 5 to 7, the study also found no difference in IQ
between children who had used Chemet, and those whose lead levels fell
naturally over time. Chelation, the study in the journal Pediatrics
concluded,
"is of no proven benefit" to children with moderate lead poisoning.
Walter Rogan, a medical epidemiologist at the National Institutes of Health
and an investigator on that study, says he doesn't believe d-penicillamine
will prove to be any more effective at lowering blood levels or improving
cognition. "There is no evidence that you can reverse the damage," Dr. Rogan
says. "It appears to be permanent."
The patient-advocacy community is similarly skeptical. In Richmond, Va., Ms.
Shabazz of United Parents Against Lead National says that lead levels in her
son, who is now 13, have fallen to below 3 mg/dl, but he still struggles in
school with short-term memory problems.
Ms. Shabazz's group works mainly with lower-income families "struggling to
make a living," she says. "Lead poisoning is invisible, so it's not at the
top
of the list of their priorities because the child is not broken or
bleeding."
Her group helps families remove lead hazards in their homes. The group is
setting up a lead safe house registry for two cities in Virginia that allows
residents to see which houses have passed muster.
Dr. Shannon, though, says he has anecdotal evidence to suggest that
cognitive
problems can improve. In his office at Children's Hospital Boston recently,
Dr. Shannon points to the table where he sits with parents after a child has
completed the d-penicillamine regimen. "They ask me the $1 million question:
'Has my child been irreversibly harmed?'" he says. Most children are 2 to 2
1/2 years old when treatment ends, too soon to tell, he says. Only after the
children start school do attention-deficit disorder, speech delays,
antisocial
behavior, learning disabilities and other damage associated with lead
poisoning emerge.
Among parents who have used d-penicillamine, no one questions the need for a
palatable recipe. Connie Orcutt of Brookline, Mass., says that getting her
7-year-old daughter to take the medicine was a constant battle. The little
girl, who was adopted from China, had a lead level of 58 mg/dl when she
arrived here. After hospitalization lowered her levels, Dr. Shannon
prescribed
d-penicillamine to try to get the lead down even further. "It is really
noxious smelling and it doesn't taste much better," says Dr. Orcutt, a
veterinarian.
She tried to mix it in food -- jam, chocolate sauce, pudding -- to mask the
smell. Every few days, her daughter would reject the latest concoction. "She
had to take it every morning and every night. She was always upset," says
Dr.
Orcutt. She notes that while her daughter did experience some rashes and
diarrhea, it was never clear if it was connected to the drug, and her
daughter's lead levels did improve.
Dr. Shannon's trial of the kid-friendly version will enroll only children
whose blood lead levels are between 15 and 25 mg/dl. If the experiment is
successful, a follow-up study could be conducted to see if the drug is
effective at treating even lower levels. Dr. Shannon estimates that up to
80%
of lead-poisoning cases fall in these low and moderate ranges. "If we show
that this drug works," he says, "it will address the majority of childhood
lead-poisoning cases in the country."
As progress on the trial moved forward, Mr. Kitterman, the financier, went
back to the Boston Harbor Angels in September to give them an update. He
reported that Dr. Shannon had applied again for an FDA grant. This time, the
application explained why he chose to study children with lower levels of
lead. And the $100,000 in seed money allowed him to lower his budget. Dr.
Shannon got his grant: $573,893 over three years to defray the costs of the
trial, which is set to begin in the spring. (An FDA spokeswoman says the
agency can't comment on specific cases.)
Mr. Kitterman added that he had also been in touch with a Paris-based
pharmaceutical company that was interested in selling the reformulated drug
in
Russia and China, where lead poisoning is an even larger problem than it is
in
the U.S. "The lead-poisoning problem," Mr. Kitterman concluded, "is not
going
away."
License this article from Dow Jones Reprint
Service[http://www.djreprints.com/link/DJRFactiva.html?FACTIVA=wjco2007121800
0048]


A CHILD IS A TERRIBLE THING TO WASTE!
Zakia Rafiqa Shabazz, Director
UPAL National, Inc.
P.O. Box 24773, Richmond, VA 23224
804-308-1518 ~ www.upal.org

-- "Ralph Scott" <rscott@...> wrote:
A Jan. 2, 2008, article on Web MD describes a new study suggesting lead
exposure as a factor in the development of Alzheimer's:
www.webmd.com/alzheimers/news/20080102/lead-link-to-alzheimers-disease

The Journal of Neuroscience article abstract about this study is available
at:
www.jneurosci.org/cgi/content/abstract/28/1/3

Ralph Scott
Acting Executive Director
Alliance for Healthy Homes
P.O. Box 75941
Washington, DC 20013
202-739-0881; rscott@...; www.afhh.org

Working for affordable healthy housing for all.

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