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 1 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 2