A gradient is a pathway of increasing concentration of a
specific substance. Overall, our findings suggest that if this
technique could be adapted to treat children with this type of LSD we would
have an effective therapy.,
President and Chief Executive Officer, will speak at the CIBC World
Markets Annual Biotechnology and Specialty Pharmaceuticals Conference
on Tuesday, April 5, 2005, at 1:45 p.

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Therefore, genetically modified BMCs would be able to produce an endless
supply of monocytes carrying the gene for beta -galactosidase, ensuring that
the enzyme would always be available to affected neurons in the brain of
children with GM1 - gangliosidosis.
Lysosomes are the cell's recycling centers, where proteins , fats and other
molecules are broken down into their basic building blocks, which are then
reused to make new molecules.
The other authors of this paper include Alessandra Tessitore (currently at
Telethon Institute of Genetics and Medicine; Naples, Italy) and Angela
Ingrassia (St. Jude is financially supported by ALSAC, its fund-raising organization. The company has
built a diverse portfolio of product candidates targeted to many types
of cancer, including three being tested in multiple ongoing clinical
trials, SGN-30, SGN-15 and SGN-40, and four in preclinical
development , SGN-35, SGN-70, SGN-75 and SGN-17/19.

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"The improvement was clearly linked
to the ability of the corrected neurons to break down excess GM1 with the
enzyme delivered by the monocytes.html).

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After the St.org/media/0,2561,453_5297_12276,00.m. The conference
is being held at the Millennium Broadway Hotel in New York.
More information about Seattle Genetics can be found at
www.com


b genetically

These cells took in the enzyme
released by the monocytes and used it to break down excess GM1, thus
correcting the potentially fatal buildup of this molecule.
"We used the brain's own signaling molecules to guide the genetically
modified monocytes along a concentration gradient to the degenerating brain
cells," d'Azzo said.
d'Azzo previously showed that GM1 - gangliosidosis is an inherited disease
in which one of the enzymes in the lysosomes is defective (Molecular Cell ,
Sept. Jude).
d'Azzo holds the Chair in Genetics and Gene Therapy endowed by the Jewelers
Fund for Children.stjude.

Seattle Genetics to Present at CIBC Biotechnology + Specialty Pharmaceuticals Conference

Seattle Genetics has
developed leading ADC technology comprised of highly potent synthetic
drugs and stable linkers for attaching the drugs to monoclonal
antibodies.

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"We showed that improvement of the disease was directly related to the
amount of genetically modified monocytes reaching the degenerating brain
cells," said Renata Sano, Ph.stjude.D.

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Jude study, the BMCs followed the gradient
toward increasing concentrations of the chemokines until they reached the site
of the degenerating neurons. Founded by late entertainer Danny Thomas and based in
Memphis, Tenn.org. (Nasdaq:SGEN) announced today that Clay B.com,
under the "news and investor information" section.

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A report on this work appears in the
prepublication online issue of Blood. Jude researchers successfully treated a laboratory model of an LSD
called GM1 - gangliosidosis using bone marrow cells (BMCs) into which
scientists inserted the gene for an enzyme that breaks down a fat molecule
called GM1. In the St.D.
St.

modified b

, a member of the St."
Key to the promise of curing LSDs in children using this technique is the
fact that since BMCs are stem cells, they continually give rise to all the
various types of blood cells in the body, including monocytes, d'Azzo said. These diseases, including
GM1 - gangliosidosis, are responsible for most severe cases of
neurodegeneration and mental retardation among children. Jude Children's Research Hospital is internationally recognized for
its pioneering work in finding cures and saving children with cancer and other
catastrophic diseases.

About Seattle Genetics

Seattle Genetics discovers and develops monoclonal antibody-based
therapeutics to treat cancer and other human diseases.

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But in GM1 -
gangliosidosis, brain cells lack this enzyme-beta-galactosidase -and GM1
accumulates to such a high concentration that it disrupts the proper function
of the cell and causes it to self-destruct.
The monocytes homed in on the brain by following a trail of signaling
molecules that were released by cells adjacent to the degenerating neurons,
according to Alessandra d'Azzo, Ph. Under a disease condition, these brain cells, called astrocytes
and microglia, release chemokines in order to trigger a migration of immune
cells to areas of the brain that are damaged . If the BMCs were harvested from the same
child who is treated with them after these cells are genetically modified,
this would eliminate the potential complications arising from transplanting
BMCs from a donor. 10, 2004; http://www. LSDs occur when lysosomes lack the enzymes they
need to perform their recycling tasks, leading to abnormal accumulation of the
molecules the lysosome is supposed to break down.
This work was supported in part by the National Institutes of Health, a
Cancer Center Support Grant, the Assisi Foundation of Memphis and ALSAC. For
more information, please visit http: //www.

Business Editors/Health/Medical Writers
CIBC World Seattle Genetics,
Inc.

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, Physicians might one day be able
to treat a disease that destroys brain cells in children using genetically
modified cells to transport a "drug" to the site of the dying neural cells
(cells that transmit impulses). This discovery occurred based on results of a
laboratory study of the technique published by investigators at St. Such signaling proteins are called
chemokines.seattlegenetics.

modified genetically

Jude team infused the genetically modified BMCs into the
laboratory model, resulting monocytes migrated to the degenerating brain cells
that lacked the gene for beta-galactosidase.D. Jude department of
Genetics and Tumor Cell Biology. Normally, the immune cells recruited to the brain
by chemokines would cause inflammation and worsen the damage. Jude Children's Research Hospital
St. Siegall, Ph.

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Jude researchers

MEMPHIS, Tenn. But in this
case, the genetically modified monocytes restored the beta -galactosidase
activity, which in turn decreased the extent of neuron degeneration and
chemokine levels. Dr.

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Immune system cells find damaged neural cells by following a trail of protein
signals released as part of inflammatory response to lysosomal storage disease
process , according to St.
There is currently no cure for such disorders, which are called lysosomal
storage diseases (LSDs)., a researcher in St.

St. Jude freely shares its discoveries with scientific and
medical communities around the world. No family ever pays for treatments not
covered by insurance , and families without insurance are never asked to pay.

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Genetically Modified Cells Migrate to Brain and Treat Neurodegeneration in St. Jude Model


Siegall will present an overview of key company programs and discuss
recent activities.

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GM1 is a critical component of normal brain cells. Jude Genetics and Tumor
Cell Biology and the paper's first author., St.

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Jude
Children's Research Hospital. d'Azzo is senior author of the
article in Blood.



A webcast of the presentation will be available live and for
replay from the Seattle Genetics website, www. The product
candidates encompass three platform technologies: genetically
engineered monoclonal antibodies, antibody-drug conjugates (ADCs ) and
antibody-directed enzyme prodrug therapy (ADEPT). The company currently has license agreements for its ADC
technology with Genentech, UCB Celltech, Protein Design Labs, CuraGen
and Bayer and for its ADEPT technology with Genencor International.

bovine genetics


The St. BMCs include a population of so -
called pluripotent stem cells-cells that give rise to a variety of different
cell types that have specific functions, such as the immune cells called
monocytes. Eastern Time.seattlegenetics .

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