Reprinted from the Wall Street Journal
By AMY DOCKSER
MeHarry Medical College AIDS Researcher, Dr. James Hildreth, collaborates with a family looking for a drug to save their twin daughters lives
From the moment her twin
daughters, Addison and 
Cassidy, were
diagnosed with a fatal genetic disease in October 2007,Chris Hempel has been searching for a drug that might save their lives.
The 5-year-old girls were diagnosed with a devastating cholesterol
metabolism disorder known as Niemann-Pick Type C, which is ultimately fatal. Soon after, Ms. Hempel
learned that researchers found that a form of a compound called cyclodextrin extended the lives of affected mice.
Ms. Hempel set out to gather as much data as possible. She got a list
of all major cyclodextrin distributors and connected with one in
Florida, who shared scientific studies and other information with her.
She found a short report in the medical literature about a doctor who had treated a child with a different disease using cyclodextrin and
tracked him down.
She became increasingly hopeful that, although cyclodextrin isn't
approved as a drug in the U.S., she might get the Food and Drug
Administration to allow her to give cyclodextrin infusions to her
girls as an experimental treatment.
Her search for information also led her to James Hildreth, 52, a
pre-eminent AIDS researcher who heads the Center for AIDS Health
Disparities Research at Meharry Medical College in Nashville, Tenn. It
turned out that he too was seeking FDA approval to run a trial using
cyclodextrin, in a vaginal cream to help prevent HIV transmission
during heterosexual sex. Ms. Hempel wanted him to combine forces with
the NP-C investigators to push forward cyclodextrin research.
That was only the beginning of Ms. Hempel's long journey through the
health-care research community -- a distributed and labyrinthine
collection of researchers who, for all their expertise, often remain
unaware of advances made elsewhere. The problem is even more acute
among researchers working on different diseases. But for some
serendipity, curiosity -- or, in this case, a willful Ms. Hempel --
some knowledge in one lab may never make its way to another that could
be on the verge of a new therapy.
Drugs approved for one disease often turn out to be effective in others -- frequently when someone has a hunch. Thalidomide, originally
used for morning sickness but taken off the market because it caused
birth defects, is being used in cancer treatment.
Researchers at Pfizer were developing Viagra to treat high blood pressure when they noticed during early tests that it treated
impotence. But that happened within the same company. It is even more difficult when researchers are at different labs.
When Ms. Hempel, who lives in Reno, Nev., became passionate about Dr. Hildreth's work, she was determined to bridge the disparate knowledge. "Right now we have limited data on cyclodextrin. But what if a lot of people started looking at it from different angles and across
different diseases?" Ms. Hempel said. "It could lead to something that
helps save Addi and Cassi's lives."
Ms. Hempel had been researching cyclodextrin for months when she
attended the June 2008 meeting in Tucson, Ariz., of the Ara Parseghian
Medical Research Foundation, set up by the family of the legendary
football coach who lost three grandchildren to NP-C disease. The
foundation was providing some funding for cyclodextrin studies in the
rare disease, and the latest data were presented there. In an email
sent after the meeting, Ms. Hempel wrote to the NP-C researchers that,
based on the data she heard, she and her husband, Hugh, planned to
seek FDA approval to give the girls cyclodextrin infusions. "I feel
very strongly that we must try this to help save Addi and Cassi from
this horrible disease," she wrote.
She had already put together a three-inch binder of research studies
about cyclodextrin. Working with three other families whose children
have NP-C disease, they hired a scientist who began writing a request
to the FDA for the Hempel children to receive cyclodextrin infusions.
But Ms. Hempel knew that she needed more human data if she was going to persuade the FDA that the drug was safe enough to use in her children.
While searching for safety data on cyclodextrin, she spoke with Charles E. Strattan, a cyclodextrin expert and CEO of CTD Holdings Inc., who was helping Ms. Hempel do research. He told her Dr. Hildreth was interested in the same compound for his work in HIV and suggested that
the two of them talk.
During a long phone conversation in October 2008, Dr. Hildreth told Ms.
Hempel that he believed the protein responsible for NP-C disease also
plays an important role in HIV. And in previously published work, he
showed that cyclodextrin appeared to inactivate the HIV virus and
prevent it from replicating.
The talk galvanized Ms. Hempel. Dr. Hildreth offered to share what he
knew about cyclodextrin's safety with the FDA in support of the Hempels' request. Ms. Hempel proposed that the two of them go to Johnson & Johnson, which had studied cyclodextrin, to see if the company would
be interested in sponsoring a clinical trial. "I knew our stories would be even more powerful if we told them together," she said.
As is typical in the field, Dr. Hildreth was reluctant to share
unpublished data, and he rarely went to scientific meetings that
weren't related to HIV. He was moved by Ms. Hempel's efforts to help
her children, but also surprised by her embrace of his work. "Some of
the things we as scientists take for granted about how work will be
done and the fact there are silos, with her there is none of that at all," he said.
When Ms. Hempel called a top National Institutes of Health AIDS
researcher to tell him about Dr. Hildreth's findings and propose joint
work in HIV and NP-C disease, Dr. Hildreth told her that a scientist
never would have made such a call. In recent months, Ms. Hempel has
introduced Dr. Hildreth to NP-C researchers who were also studying
cyclodextrin. She also arranged for him to discuss his HIV findings
with two Nobel Prize-winning scientists interested in Niemann-Pick
proteins. "Our paths would not have crossed otherwise," he said.
He and Ms. Hempel recently had a conversation with senior officials at
Johnson & Johnson. The FDA at first turned down the Hempels' request
to do cyclodextrin infusions in the girls, concerned there wasn't
enough human safety data. But after Ms. Hempel contacted them about
her plight, the company wrote a letter to the FDA giving the agency
permission to look at all of the safety data it had submitted related
to cyclodextrin. The FDA subsequently gave permission for the Hempels
to proceed. The girls will start cyclodextrin infusions this month.
That might have been the end of the story except for Ms. Hempel's
insistence that more was at stake, says Steven A. Silber, a vice
president at Johnson & Johnson. After listening to Ms. Hempel and Dr.
Hildreth's presentation, Dr. Silber set up a meeting so Dr. Hildreth
can present his data to the head of one of its companies that makes
anti-viral medications. Dr. Hildreth says that Ms. Hempel's
involvement got his research "the attention of individuals higher up
in the organization than I might have been able to get on my own."
This May, the Parseghian Foundation will host its annual scientific
meeting. The group plans to hold a special session dedicated to the
work on cyclodextrin. Cindy Parseghian, president of the foundation,
says she hopes researchers working with cyclodextrin in other diseases
will also attend. "We think there should be more cross-fertilization," she said. Dr.
Hildreth says he plans to share his findings at the meeting.
Dr. Hildreth recognizes that his unusual partnership with Ms. Hempel
also has some risks for the HIV trial he is planning. "It is a remote
possibility, but is a possibility, that if her beautiful girls are
done some harm by the infusions, that would clearly do harm to our
efforts," he said. Still, he adds, "I spent a lot of time thinking
about what I would do if I were in her position. My answer is I would
do exactly the same thing."
Late last month, the Hempel girls underwent surgery at a California
hospital to get a small medical device implanted under their skin to
make it easier to receive regular cyclodextrin infusions. Dr. Hildreth
visited them in the hospital.
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