Telomerase

From: Zeb Haradon (zharadon@inconnect.com)
Date: Fri Feb 18 2000 - 01:23:30 MST


This makes me drool with telomerase lust:
http://biz.yahoo.com/bw/000217/ca_geron_2.html

Telomerase Prevents Onset of Liver
Cirrhosis in Mice

MENLO PARK, Calif.--(BW HealthWire)--Feb. 17, 2000--Geron Corporation
(Nasdaq: GERN
- news) reported the publication of independent scientific research that
supports the potential role of
telomerase as a therapeutic agent in liver cirrhosis. The research,
performed by scientists at the
Dana-Farber Cancer Institute of Harvard Medical School and Albert Einstein
College of Medicine
and published in the February 18 issue of Science, provides evidence of the
efficacy of telomerase
therapy in a mouse model of cirrhosis, a chronic liver disease.

Geron provided funding for development of the original telomerase knock-out
mouse which led to
this study, and has exclusive intellectual property rights to key human
telomerase assays, proteins
and genes, as well as therapeutic applications of these molecules.

Telomerase is an enzyme that synthesizes telomeric DNA at the ends of
chromosomes and thereby
confers extended replicative capacity to cells. In the absence of
telomerase, telomeres gradually
shorten until a critical limit is reached and cells stop dividing and either
die or senesce. Numerous in
vitro and in vivo studies have established a strong correlation between
telomere erosion and cellular
aging and disease, but this report is the first published evidence that
introduction of telomerase by
gene therapy in an animal model prevents the onset of a serious chronic
disease. Liver cirrhosis in
humans is typically caused by hepatitis or chronic exposure to alcohol, and
is the seventh leading
cause of death by disease. There is currently no adequate treatment.

In previous work led by the senior author of this study, Dr. Ron DePinho, it
was shown that although
mice normally have very long telomeres, short telomeres could be achieved by
eliminating the gene
for one of the components of mouse telomerase. Eventually, critically short
telomeres are reached
and the mice display several age-related disorders similar to those seen in
elderly humans, including:
an increase in hair graying and loss, ulcerative skin lesions, chromosomal
fusions and cancer; and a
decrease in body weight and lifespan. The mice also showed a decreased
ability to recover from
stress which resulted in a decreased regenerative capacity of hematopoietic
(blood) and
gastrointestinal systems, including the liver, as well as a decreased wound
healing capability.

In previous experiments, in three separate disease models of chronic stress
to the liver, mice with
short telomeres were shown to have impaired capacity to recover from such
stress compared to
mice with long telomeres. DePinho's team has now demonstrated that when DNA
for the telomerase
gene is delivered by gene therapy to the telomerase knock-out mice, the mice
become equally
capable of recovery following liver stress as are normal young mice with
long telomeres.

``This study is important for two fundamental reasons,'' noted Calvin B.
Harley, Ph.D., Geron's chief
scientific officer and a pioneer in telomere and telomerase biology.
``First, it shows telomere loss can
be the key factor in chronic age-related diseases. In this in vivo model,
the only difference between
the experimental mice and the control mice is the lack of telomerase which
results in significant
telomere loss. This difference generates disease conditions similar to that
seen in humans. Second, by
showing that telomerase gene therapy can prevent cirrhosis in these mice, it
provides a model system
to test the safety and efficacy of telomerase therapy in humans, not just
for liver disease, but for
multiple other disorders in which telomere loss is implicated.''

In DePinho's studies, the gene for the RNA component of mouse telomerase
(mTR) was first
genetically deleted, and then, later, delivered by gene therapy just before
telomeres became critically
short. In humans, the natural repression of telomerase activity in cells is
largely controlled by turning
off the gene for the catalytic protein component of telomerase (hTERT).
Geron scientists cloned the
hTERT gene in 1997 in collaboration with researchers at the University of
Colorado, Boulder.
Subsequently, in collaboration with investigators at the University of Texas
Southwestern Medical
School at Dallas, Geron scientists showed that hTERT alone was sufficient to
extend the healthy
lifespan of numerous cell types, without inducing cancerous changes in the
cells (Bodnar, et al 1998,
Science 279:349-352; Jiang, et al 1999, Nature Genetics 21:111-114). These
discoveries have
opened the door for the development of therapeutics to treat numerous
degenerative diseases of
aging by cell, gene, protein, or small molecule (drug-like) therapies that
result in telomerase
activation.

Geron has an extensive intellectual property portfolio of more than 40
issued patents and numerous
pending patent applications covering telomerase, including the mouse model
used in these recent
studies. Geron's patent portfolio includes patents and applications covering
both the RNA and
protein components of human telomerase, the genes encoding these human
molecules, and methods
of modulating cell function by administering these molecules to cells.

Geron Corporation is a biopharmaceutical company focusing on discovering,
developing and
commercializing therapeutic and diagnostic products to treat cancer and
other age-related chronic
degenerative diseases. Geron's technology platform includes the discovery of
small molecule
inhibitors of telomerase for cancer therapy; telomere and telomerase-based
research and diagnostic
tools; telomerase activation to extend the replicative lifespan of normal
cells; and complementary
stem cell, gene therapy and nuclear transfer approaches to restore the
function of degenerating
organs.

Statements in this press release regarding product development and future
applications of Geron's
technology constitute forward-looking statements that are subject to certain
risks and uncertainties.
Actual results may differ materially from the results anticipated in these
forward-looking statements.
Additional information on potential factors that could affect the company's
results is included in the
company's quarterly report on Form 10-Q for the quarter ended September 30,
1999.

To receive an index and copies of recent press releases, call Geron's News
On Demand toll-free fax
service, 1-800-782-3279. Additional information about Geron Corporation can
be obtained at
http://www.geron.com.

Contact:

     Geron Corporation
     Nancy Robinson, 650/473-7700
          or
     Burns McClellan
     Dennis Schwartz, 212-213-0006

Also see (more anti-aging):
http://dailynews.yahoo.com/h/nm/20000216/sc/science_aging_1.html

--------------------------------------------------------------------------
Zeb Haradon
My personal website:
http://www.inconnect.com/~zharadon/ubunix/
A movie I'm directing:
http://www.elevatormovie.com



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