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: > > >

TheBurnhamReport

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