Leukemia treatment on the fast track
At the vanguard of stem cell research
A new drug forAlzheimer’s
Leukemiameets its
match.
In this edition of The Burnham Report,you’ll find exciting news of medications
making their way to the clinic, thanks in
part to the contributions of Burnham
scientists. A new drug for Alzheimer’s,
the first that actually prevents the death
of brain cells, is currently in use in
Europe and recently received FDA
approval. A treatment for a common
form of leukemia has been fast-tracked
for FDA approval; this treatment is
showing efficacy in clinical trials against
many other forms of cancer as well.
The Institute recently launched a
program in human embryonic stem cell
research, which we expect will lead to cell
replacement therapies for many currently
incurable diseases. I hope you are as
heartened as I am by these advances.
On behalf of all at The Burnham Institute,
I thank you for your interest and support.
JOHN C. REED, M.D., PH.D.
President and CEO
F R O M R E S E A R C H ,
T H E P O W E R
T O C U R E .
IN THIS ISSUE: > > >
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THE BURNHAM INSTITUTE
FALL 2003 Vol. 1, No. 2
A new treatment should soon be available for a common form of leukemia. Based on the pioneering
work of Professor and CEO John Reed, the new therapy, called Genasense, received “Fast Track”
designation from the FDA in June, 2003.
Genasense works by blocking the
production of a protein called Bcl-2,
which is made in high levels by many
cancer cells. Bcl-2 prevents cell death
and, at high levels, protects cancer cells
from chemotherapeutic drugs. Clinical
trials have shown that Genasense and
traditional chemotherapy, administered
in conjunction, can effectively reduce
the number of cancer cells in patients
with CLL (chronic lymphocytic
leukemia), the most common form
of adult leukemia.
Genasense is displaying efficacy in
clinical trials for other leukemias as well,
and for cancers including myeloma,
melanoma, lymphoma, and prostate,
breast, lung and colon cancers. This
promising treatment had modest
beginnings. As a postdoctoral fellow,
Reed first derived its concept but
encountered difficulty obtaining
support. Genasense is likely to be the
first approved treatment of a class
based on what is known as anti-sense
DNA technology. Conventional drugs
bind to proteins and inactivate them,
but anti-sense DNAs prevent the
production of proteins.
“It was an emerging idea,” recalls
Reed,“and people were skeptical.”But
he persisted and eventually obtained
the $2,000 needed to purchase
reagents that would enable him to
test the idea. After initial experiments
showed promise, Reed was successful
in obtaining a grant from the National
Cancer Institute.
If approved for CLL, Genasense will
likely be used to treat thousands of
patients—approximately 50,000 people
in the U.S. are living with CLL. The
disease affects the white blood cells that
normally produce antibodies. Their
abnormal growth alters the develop-
ment and function of normal blood
cells, compromising patients’ immune
systems, and thereby their ability to
fight off infections. Treatment with
Genasense kills the leukemic cells.
“I’ve been working on the concept
of anti-sense to Bcl-2 for almost 14
years,” said Reed. “It’s highly gratifying
to see this treatment so close to avail-
ability for patients and their families.”
Researchers examine
the effects of anti-
sense DNA agents
on cancer cells.
TheBurnhamReport
G I V I N G W I T H A G L O B A L V I S I O N
M A L I N B UR N H A M
Malin Burnham was first elected a Trustee of
The Burnham Institute in 1982 and served as
Board Chairman from 1983-1986 and 1987-
1994. One of his many important contributions
has been leading the effort to expand the
Institute’s base of support in the greater San
Diego area and beyond. In addition, Malin has
been a strong advocate of amplifying the
Institute’s technology transfer effort, to ensure
that the results of basic research find applica-
tion in the form of new drugs and diagnostics.
Malin is well-known to the San Diego
community as the president and CEO of John
Burnham & Company Insurance and Burnham
Real Estate Services. He has received numer-
ous honors for his civic and philanthropic
leadership, including the 1999 Model Citizen
Award from the Alexis de Tocqueville Society
and the 2000 Philanthropist of the Year
award from the National Society of Fund
Raising Executives.
In 1995, Malin and his family pledged a
lead gift in the Institute’s re-naming campaign.
“It has been especially satisfying for me to
see the enjoyment my children and grand-
children derive from participating in the
significant venture of helping to cure
disease,” he said. “We are involved in many
activities in the San Diego area, but I
like to think that by supporting scientific
research, we are helping to benefit people
throughout the world.”
F R O M R E S E A R C H ,
T H E P O W E R
T O C U R E .
Evan Snyder (right) and
his stem cell team
are making regenerative
medicine a reality.
Working with stem cells, Burnham
Professor Evan Snyder and his team
have restored, to partial but consider-
able degree, the ability of paralyzed rats
to walk. The team is among a group
of scientists, at The Burnham Institute
and elsewhere, who have achieved
impressive successes in animal models
of debilitating conditions. Before the
promise of stem cells can be realized in
people, however, research must be done
using human cells. Snyder and his col-
leagues recently initiated a program of
human embryonic stem cell research
that positions The Burnham Institute as
one of the hubs of a worldwide effort.
Human embryonic stem cells are
derived from fertilized eggs produced
during IVF (in vitro fertilization)
that are not implanted in a woman’s
womb. Couples who have undergone
IVF and decided they have completed
their families routinely have embryos
remaining in frozen storage. A recent
study estimated that more than
400,000 embryos are currently stored
in the United States.
Embryos at this early stage—called
blastocysts—are roughly spherical
clusters of between 16 and 64 cells.
Some of these cells can be cultured in
laboratory dishes, and have the ability
to give rise to many of the different
cell types that exist in the body. Thus,
new heart, brain, muscle and skin
tissue can be derived from stem cells,
and used, it is hoped, to replace tissue
lost to disease or injury.
Adult stem cells are found in vari-
ous locations in the adult body, and
some studies have suggested that stem
cells from one organ can “transform”
under certain conditions to cells of
a different type. Other studies have
called these results into question.
“At this point in time, we believe
stem cells obtained from an embryo
or a fetus are the most plastic, with the
potential to be used for the widest range
of diseases,”said Professor Evan Snyder,
director of the Institute’s Stem Cells
and Regeneration research program.
Since the National Institutes of
Health can only fund work with
human lines derived before August 9,
2001, most of the human embryonic
stem cell work at Burnham will be
privately funded. To date, five human
stem cell lines have been procured.
In their initial projects, Burnham
investigators are exploring methods of
directing the cells to develop along
specific paths, including neural, cardiac
and pancreatic. The hope is to develop
cells that could be used to treat neu-
rodegenerative diseases, heart failure,
and diabetes, respectively.
Before any line of stem cells is used
to treat patients, however, they must
be shown to be free of contaminants.
All of the currently federally approved
lines have been grown using mouse
cells as “feeder” or support layers, and
these cells could release dangerous
viruses and other pathogens. Therefore
the Burnham stem cell team is devel-
oping protocols to grow embryonic
stem cells using human feeder layers.
Other important steps before clinical
translation is possible include showing
that the stem cells do not become
the wrong cell type in a given organ
(for example, heart cells in the brain),
and that they do not make tumors.
The Burnham Institute has provided
an infrastructure for some of the region’s
most talented researchers in stem cell,
developmental, and regenerative biology
in order to collaborate as the Southern
California Stem Cell Consortium. The
consortium meets monthly to exchange
ideas and foster joint projects. For
example, The Burnham Institute will
host one such collaborative effort—in
this case, between The Burnham
Institute and the Children’s Hospital
of Orange County—which is one of
only five NIH-funded courses on
human stem cells (intended for the
international community).
T H E D E L E . W E B B C E N T E R F O R N E U R O S C I E N C E A N D A G I N G
At the hubof international
research.
> > >
R E S E A R C H H I G H L I G H T S
The Burnham Institute has received a five-
year $500,000 grant for cancer research
from the Bristol-Myers Squibb Foundation.
The award will provide seed funding for the
cancer drug discovery initiative, which
seeks to accelerate the translation of basic
cancer biology research into new clinical
therapies. “Our cancer drug discovery effort
brings together the talents of biologists,
chemists, biophysicists, and computational
biologists, to discover new ways of treating
cancer,” said President and CEO John C.
Reed. “With this grant, Burnham scientists
will have the resources to move more of our
discoveries into pre-clinical testing.”
Professor Manuel Perucho was named
recipient of the Cancer Research
Professorship in Basic Cancer Research for
2003.The $50,000 award, conferred jointly
by the American Association for Cancer
Research and the National Foundation for
Cancer Research, is given annually through
peer nomination. Dr. Perucho was recog-
nized for his pioneering contributions to the
field of cancer genetics, and the award will
further his research on mechanisms underly-
ing gastrointestinal cancer.
A team of Burnham scientists has secured
a multi-million dollar grant to develop
new potential treatments for anthrax.The
$3.3 million, from the National Institute of
Allergy and Infectious Disease, will enable
the investigators to screen more than a
million drug candidates during three and
a half years.The effort is led by Professor
Alex Strongin (shown below); he is joined
by Professor Robert Liddington, Associate
Professor Maurizio Pellechia and collabora-
tors at The Scripps Research Institute.
Professor Barbara Ranscht has been
awarded a grant from the Christopher
Reeve Paralysis Foundation.The grant of
$75,000 will support work in Ranscht’s
laboratory aimed at deciphering the
molecular codes that govern how nerves
can grow and form functional connections
after spinal cord injury.
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F R O M R E S E A R C H ,
T H E P O W E R
T O C U R E.
>
T H E B U R N H A M R E P O R T
JOHN C. REED, M.D., PH.D.
President and CEO
CHERYL A. MOORE
Senior Vice President and COO
TERRY GACH
Vice PresidentResource Programs
SUZANNE CLANCY, PH.D
EditorThe Burnham Report
LIPMAN HEARNE, INC.
Graphic Design
BOB ROSS
Photography
www.burnham.org