CAHB Newsletter June 2005 Volume 2 Number 3

CAHB Newsletter
June 2005
Volume 2 Number 3
differences in his results and that of the paper’s, he felt the
urge to challenge the professor and took the trip to Stanford
to talk to him in person. He ended up staying and working
under him as a research fellow.
Table of contents
- Announcement
- Lecture Report
- Bio News Top Picks (June 2005)
- Acknowledgment
Dr. Nakai explained how his experiments have shown that
the non-integrated parts of AAV are the most important for
the generation of the high transduction efficiency. Generally
it was thought that to maintain the stable proliferation of the
introduced genes, it was essential for the introduced gene to
integrate with the host cell’s original DNA. But in reality,
his experiments show that the non-integrated parts of AAV
are the crucial parts to the transduction process.
Announcement
We, Center for the Advancement of Health and Biosciences
(CAHB), is working hard, day and night, to prepare new
activities. We will announce the detail of the activities in the
coming issues of CAHB Newsletter, as well as at our web
site (http://www.cahb.org/). Please stay tuned.
The high efficiencies that the virus vector produces ensure a
promising future for the AAVs roles in gene therapy. But to
be used in gene therapy, Dr. Nakai says, AAV still poses
problems, such as the probability that the introduced DNA
integrates to a cancer related gene. The triggering of cancer
by gene introduction have actually happened before when a
retrovirus was used for gene therapy of ten patients with XSCID in France and treated patients started developing
leukemia. Dr. Nakai and other researchers are continuing
research to figure that out.
Hiroaki Masuda: hmasuda@cahb.org
Lecture Report
Adeno-Associated Virus Vectors:
Amazing vehicles for gene delivery in vivo
Hiroyuki Nakai M.D., Ph.D.
Stanford University Senior Research Fellow
Held at Stanford University on June 6, 2005
The lecture was a great success thanks to the Science and
Medical Associates Program (SMAP).
Keitaro Nakamoto: knakamoto@wesleyan.edu
This was sadly the last lecture at Stanford by Dr. Nakai who
is leaving Stanford for the University of Pittsburg at the end
of the week of June 6, 2005. Dr. Nakai talked about the
benefits of using the Adeno-Associated Virus (AAV) as a
vector for DNA introduction into animals. In a short time
span of an hour, he summarized the basics of what he has
been working on in his past eight years.
Bio News Top Picks (June 2005)
1. Breast Cancer Uses Growth Factors to Lure Stem Cells
Growing cancer tumors cannot stand alone. They need a
supporting framework of blood vessels and fibroblasts to
grow and reach metastasis. These are provided by stem
cells. Without the stem cells to build the “nest” for the
tumor, the tumor only grows to a certain size and is not
life threatening.
The AAV, with a single stranded DNA, is a non-pathogenic
virus that is very effective as a vector for gene delivery
because of its non-toxicity and its high transduction
efficiencies. It is very small at about 20nm in diameter and
can only reproduce when in contact with the adenovirus. Its
long-term stable transduction capabilities make it a very
good vector. Experiments have shown that serotypes 8 and 9
of the AAV have yielded results of close to a 100% in
transduction efficiencies in skeletal muscle, cardiac muscle,
smooth muscle, the pancreas, and the brain. Slides presented
at the lecture showed liver tissue crowded with blue dye
showing the amount of transgenes introduced into the cells.
It was easily recognizable that most of the cells contained
the blue-stained transgenic DNA in them.
Scientists found that fibroblasts growth factor 2 (FGF2) and
vascular endothelial growth factor (VEGF) are secreted by
breast cancer cells which bind to and attract stem cells.
Why stem cells migrate has not been answered.
Different cancers use different growth factors to lure
stem cells. For example, melanoma cancer cells use
VEGF but not FGF2.
Knowing specifically what factors play roles in each
type of cancer is valuable because chemotherapy has
moved from concentrating on stopping cell division to
blocking its communication pathways instead. For
example, making use of antibodies or other small
molecules to block growth factor receptors.
Dr. Nakai’s recent experiments were initially spurred when
he read a paper written by Stanford professor Mark A. Kay
back when he was researching AAV on his own, while
working at Avigne, Inc. in Alameda, CA. Noticing the
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Scientist feels a need to look at cancer at the cellular
level for alternative methods to chemotherapy, radiation
therapy, or surgery.
2.
Pfizer prides itself in undertaking a six-year project for
PAH treatment that is commercially insignificant
because of the disease’s rarity. Revation demonstrates its
commitment to developing treatments for unmet medical
needs regardless of commercial potential.
Pollution-eating bacteria produce electricity
Scientists studying microbes that could be used to
eliminate pollution from waterways surprisingly found
that some pollution-eating bacteria can generate electricity.
They presented their findings at the 105th general meeting
of the American Society for Microbiology.
The FDA based their approval on a large randomized
placebo controlled study involving 277 patients of PAH.
After twelve weeks of treatment, the treated groups showed
highly significant improvements in the six minutes walk
distance, the standard measure of efficacy in PAH trials.
There were no differences in the different dosage groups.
The bacteria continuously generate electricity at levels
that “could be used to operate small electronic devices”
as long as they are fed.
Patients also showed improvements in mean pulmonary
artery pressure and other measures of cardiac function.
The unique part about this discovery by Charles Milliken
and Harold May of the Medical University of South
Carolina is the bacterium. The Desulfitobacterium was
never known to produce electricity and was commonly
known for its ability to breakdown some of the most
problematic pollutants such as PCB. They eat a large
number of different foods which means that they can be
used to clean waste and use it to generate electricity.
It is the first oral treatment for PAH to be approved for
patients with an early stage of the disease.
Keitaro Nakamoto: knakamoto@wesleyan.edu
Acknowledgment
Publication of CAHB Newsletter is made possible by CLEA
International, Inc., a subsidiary of CLEA Japan, Inc. Central
Institute for Experimental Animals (CIEA), a not-for-profit
incorporated foundation in Japan, also greatly supports
CAHB activity.
3. Doctor stored organs in cellar
Professor Dick van Velzen was accused of carrying out post
mortem examinations unreported and keeping children’s
organs without their parents’ consent. He worked for six
years at Liverpool’s Alder Hey Childrens’s Hospital
between 1988 and 1994. He has refused to appear in a
hearing before a General Medical Council (GMC) panel.
This
picture
shows
SDT/Jcl Type 2 Diabetic
Model rat. In 1988,
twelve-month-old
male
rats,
which
exhibited
polydipsia,
polyphagia,
polyuria, and glucosuria,
were found in SpragueDawley rats by Shinohara at the Research Laboratories of
Torii Pharmaceutical Co., Ltd., Japan. CLEA Japan obtained
the strain at F24 from Torii Pharmaceutical Research
Laboratories in 1998 and started distributing the animals as
SDT/Jcl rats from 2005.
A former lab officer at Alder Hey, Paul Dearlove, gave
evidence of professional misconduct at a hearing on
Wednesday. According to Dearlove, Prof. van Velzen
told him “Nothing was to be thrown away when he had
finished with a post mortem”. Which started a collection
of pots in the cellar of the lab on Myrtle Street.
Mr. Dearlove told the GMC that most of the jars
contained organs from about 1000 patients and fetuses
collected from a local women’s hospital. “It was damp
down there so the labels came off on a few of them. The
cellar was filthy and there was so much material in some
of the pots that it was in quite a bad condition.”
Dearlove said. He also said that only around 10% of his
post mortems were actually reported. If found guilty,
Prof. van Velzen could face a ban from practice.
CLEA Japan, Inc.
CIEA
http://www.clea-japan.com/
http://www.rash2.com/CIEA.htm
Center for the Advancement of Health and Biosciences
525 Middlefield Road, Suite 100
Menlo Park, CA 94025, USA
Phone: +1-650-321-2165
Fax: 650-321-2297
Email: info@cahb.org
URL: http://www.cahb.org/
4. FDA Approves Pfizer Inc.'s Revatio As Treatment
For Pulmonary Arterial Hypertension
FDA approved Pfizer’s new drug, Revation, as a
treatment for pulmonary arterial hypertenstion (PAH).
PAH affects 100,000 people worldwide causing
difficulty in breathing, dizziness and fatigue, due to
insufficient oxygen exchange in capillaries in lungs. Left
untreated, patient survival time is less than three years.
Editor in Chief: Hiroaki Masuda
masuda@cahb.org
©2005 Center for the Advancement of Health and Biosciences
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