Senator Frist to Back Stem Cell Bill

Top Republican senator, Dr. Frist has backed a bill easing restrictions on embryonic stem cell research, in a move that breaks rank with President George Bush. Bill Frist, Senate Majority leader and surgeon, formally announced his decision in the Senate on Friday. He said he was pro-life but at the same time believed stem cell research "should be encouraged and supported". President Bush has threatened to veto stem cell legislation already passed in the House of Representatives. The new legislation would allow expanded financial support for embryonic stem cell research. Dr. Frist's support for the bill puts him at odds with legislation passed by the Bush administration in 2001 restricting human stem cell research. Speaking in the Senate, Dr. Frist said: "I am pro-life, I believe human life begins at conception. I also believe that embryonic stem cell research should be encouraged and supported." He added that "to me it is not just a matter of faith, it is a matter of science ". Speaking earlier on ABC's Good Morning America program, Dr. Frist said: "This research is promising, embryonic stem cell research as well as adult stem cell research. "Now is the time to expand the president's policies because it's promising research; but it must be done in a way that is ethically considerate." Dr. Frist added that only stem cells from embryos that "would otherwise be discarded" should be used. Ethical boundaries A heart-and-lung transplant surgeon, the senator is seen as a likely presidential candidate when President Bush's second term comes to an end in 2008. His views could put him on a collision course with the White House and the Christian Conservatives whose support he would need if seeking nomination as a presidential candidate. In 2001, Dr. Frist set out his belief in the value of embryonic stem cell research within certain ethical boundaries. The new bill would ease restrictions on state funding for research carried out using stem cells from embryos left over from in-vitro fertilization treatments. Supporters argue that stem cells, which have the unique ability to develop into any kind of cell, offer the prospect of a cure to conditions including cancer and Alzheimer's disease. Those who oppose the research argue that the process of extracting the stem cells destroys the embryo and so takes a life.

Neural Stem Cells for Brain Repair By Gail Schechter, Ph.D. President, BioIntelligence Gail Schechter, Ph.D., is President of BioIntelligence (www.BioIntelligence.com), a consulting company specializing in CNS technology assessment, product development, and grant writing. She started her career at the NIH doing clinical research and subsequently worked in the pharmaceutical industry setting up research collaborations. For the past 10 years, she has helped many companies obtain multi-million dollar grant awards. She can be reached at Brains@BioIntelligence.com. An unlimited source of cells suitable for transplantation into the central nervous system (CNS) can be derived from embryonic stem cells. Of particular importance, embryonic stem cells can differentiate into diverse neuronal and glial cell types. These cells show a remarkable ability to proliferate, differentiate, migrate and integrate in the brain, as well as ameliorate functional deficits when transplanted into animal models of neurological disorders. In spite of recent progress in neural cell transplantation, extensive preclinical investigation is necessary to determine the optimal factors to control the differentiation process, insure safety, and demonstrate long-term effectiveness. Before clinical trials are initiated, there is much to learn about how to direct stem cell proliferation and differentiation into specific phenotypes, induce integration into existing neural and synaptic circuits, and optimize functional recovery in animal models closely resembling the human disease. In addition to embryonic stem cells, there are (slightly older) fetal stem cells and (much older) adult stem cells, each with its own set of benefits and limitations. In honor of Christopher Reeve, this report will highlight research advances in spinal cord injury, stroke and Parkinson’s disease. Other promising therapeutic targets for neural stem cells include amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer’s disease. Taken together, evidence is mounting that neural stem cells are capable of replacing damaged neurons, are suitable for gene therapy, and can serve as a vehicle for drug delivery to the CNS. Stem Cell Transplantation and Other Novel Approaches to Spinal Cord Injury Although Christopher Reeve did not live to walk again, he managed to turn the world’s attention to the need for more research in spinal cord injury and the potential of stem cell treatments. To date, experimental results suggest that stem cell transplantation and other new approaches can be beneficial in promoting recovery from spinal cord injury. Research from the group at Washington University School of Medicine, including John McDonald (now at Johns Hopkins) shows that embryonic stem cells can give rise to neural precursor cells and that transplantation of these cells into the injured spinal cord leads to partial recovery of function. In particular, the focus on optimizing remyelination through transplantation of myelin-producing cells may offer a practical approach to restoring meaningful neurological function. When transplanted into the injured spinal cord of adult rodents, the neural precursor cells are capable of differentiating into oligodendrocytes and myelinating host axons. Using an alternative approach to embryonic stem cells, Mark Tuszynski and his colleagues at UCSD have investigated a combination of therapeutic modalities to treat spinal cord injury. This group focuses on neurotrophic factors, including BDNF, GDNF and others, and reports that these growth factors, administered alone or in combination with cellular therapy, show a positive effect. In one study using an ex vivo gene delivery approach to provide both trophic support and a cellular substrate for axonal growth, they implanted primary fibroblasts genetically modified to secrete GDNF into animal models of spinal cord injury. The GDNF-expressing grafts promoted significant regeneration of several spinal systems compared to the control condition, and also induced Schwann cell migration to the lesion site, leading to remyelination of regenerating axons. In another study, they tested whether a combinatorial approach of stimulating the neuronal cell body with cAMP and the injured axon with the neurotrophic factor NT-3 would extend axonal growth into and beyond sites of spinal cord injury that had been grafted with autologous bone marrow stromal cells. The results demonstrated that significant axonal regeneration could be achieved by these combinatorial approaches. Fetal Stem Cells to Treat Stroke Recently, neurosurgeon Gary Steinberg and his colleagues at Stanford University School of Medicine reported the first success using fetal stem cells to re-populate the damaged region in a rat stroke model. The investigators demonstrated that fetal stem cells injected into the brains of rats could migrate to the correct location and turn into the appropriate types of neurons. Steinberg believes signals from the damaged cells act as a distress call beckoning the transplanted cells. Other signals direct the newly arrived cells to transform into neurons and astrocytes. Steinberg’s is the first paper to show that the fetal stem cells can transform into the appropriate cell types in an animal. The next step is to test whether the implanted neurons can also replace the function of the lost cells in animal models before advancing to human clinical trials. Fetal stem cells are more advantageous than adult human stem cells because they are still able to form many types of brain cells, but they circumvent the federal restrictions and controversy associated with using embryonic stem cells in humans. Stem Cells, Inc., a company founded by study co-author and pathology professor Irving Weissman, initially isolated these cells from human fetal tissue. The company now grows the cells in bulk and distributes them to researchers studying spinal cord injuries as well as Parkinson’s, Alzheimer’s and other brain disorders. Dopaminergic Neurons from Embryonic Stem Cells to Treat Parkinson's Disease Much of the initial promise of stem cell transplantation in the CNS started with Parkinson’s disease. Progress with human fetal tissue transplants in hundreds of patients (although results were mixed) provided a foundation for subsequent testing of embryonic stem cells in animal models. Recent studies in a number of laboratories have now demonstrated the ability of embryonic stem cells to differentiate into dopaminergic neurons. Following transplantation, these cells have been shown to survive, release dopamine, and reverse motor deficits Parkinson’s disease animal models. The ability to induce efficient differentiation of dopaminergic neurons requires sensitive control over growth factors and culture conditions and/or genetic manipulation. Thus, the combination of genetic engineering and appropriate culture conditions are necessary to generate a robust dopaminergic cell source derived from embryonic stem cells for cell replacement therapy of degenerative diseases such as PD. In several studies, scientists have transplanted stem cells into the brains of rats with a Parkinson-like syndrome. The cells differentiated into fully mature neurons that produced dopamine, the missing chemical messenger of Parkinson's disease. The treated animals showed functional improvement as well. While these results are encouraging, more work needs to be done before this technique becomes accepted procedure for humans with Parkinson's disease. Conclusion The unique features of embryonic stem cells are of extraordinary scientific, clinical, and commercial interest. Hopefully, their promise and potential will translate into discoveries in neural repair to treat a wide range of intractable neurological disorders. * Please reference or credit any material, article or figure cited from http://www.medicineandbiotech.com as: Copyright 2004. MedicineandBiotech.com, http://www.medicineandbiotech.com/ Disclaimer: MedicineandBiotech.com is managed by AstraGen LLC. Please re-distribute this e-magazine. AstraGen LLC and MedicineandBiotech.com do not assume, and hereby disclaim, any liability for any loss or damage caused by errors or omissions in any material published at the web-site http://www.medicineandbiotech.com, whether such errors or omissions resulted from negligence, misstatements or other oversights.

JOINT SWEDISH/CALIFORNIA SYMPOSIUM ON STEM CELLS RESEARCH: April 26th-27th, 2005, San Francisco

Bridging Forefront Scientific Achievements with Biotechnology Business Opportunities Date: April 26 - 27, 2005, CA Location: The Hyatt Regency San Francisco Airport Hotel,San Francisco, California For more information, please email: symposium@medicineandbiotech.org Website Registration: www.medicineandbiotech.org *Early Registration Discount Ends March 27th, 2005 San Francisco, CA - This April, the world’s leading stem cells researchers from Sweden and California will join pioneers from the fields of life sciences, finance and the legal community to map out the future of stem cells research and development in California. The 2005 Stem Cells Symposium, on April 26-27 th , is organized by the Consulate General of Sweden in San Francisco, the Swedish-American Chamber of Commerce in San Francisco/Silicon Valley, the Swedish Office of Science and Technology in Los Angeles and Astragen LLC and will bring together the scientific and business expertise required to build bilateral world-class research programs that foster entrepreneurship. The Symposium will feature six keynote addresses from world-renowned researchers and leading experts in the stem cells field, and over 12 other researchers and business representatives will address cutting-edge issues in a series of panel discussions. The Symposium will also arrange meetings of researchers, companies and potential financiers to spark international research and business ventures, both in the context of California's "Proposition 71" funding and beyond. "Sweden has one of the most advanced Stem Cells research programs in the world today," says Dr. Kent Persson, member of the Board of Directors at Astragen LLC and the Chair of the Symposium’s Advisory Committee. "The Symposium will attract top level stem cells researchers and bring together both Swedish and Californian businesses with Stem Cells Research for world class entrepreneurial ventures," says Dr. Neerja Sethi, member of the Board of Directors at Astragen LLC and the Symposium’s Advisory Committee. "This is a unique opportunity for Swedish and American stem cells researchers and entrepreneurs to exchange knowledge for continued expansive stem cells research," says Mr. Nils Welin, Executive Director Swedish American Chamber of Commerce. "We look forward to bringing together researchers, companies, policy makers and others from Sweden and the US in this very important area. Due to California’s Proposition 71 stem cells funding initiative, there is a great potential to form joint ventures between Swedish and US concerns. Progress in the stem cells area will most likely lead to major health benefits and economic growth in our countries," says Helena Jonsson-Franchi, Swedish Attaché of Science and Technology, at the Swedish Office of Science and Technology in Los Angeles. This will be a "continuing symposium," with follow-up meetings in future years to map progress and continue to steer the course for future international cooperation in this important area of scientific, business and governmental cooperation The two day symposium will be held in the San Francisco Bay Area and is scheduled to take place in mid-late April 2005. To learn more about the Stem Cell Symposium, please visit the following link: www.medicineandbiotech.org Consulate General of Sweden in San Francisco The Consulate General of Sweden in San Francisco provides services to Swedish citizens and conducts extensive information and culture activities, arranging and supporting Swedish events in the San Francisco Bay Area. Swedish-American Chamber of Commerce San Francisco/Silicon Valley The main objective of the Swedish-American Chamber of Commerce in San Francisco/Silicon Valley is to foster trade between Sweden and the US and to enhance the business interests of its members. By providing a broad spectrum of services and new business opportunities through networking, the Chamber contributes to the development and improvement of goodwill between the business communities in the San Francisco Bay Area and Sweden. Swedish Office of Science and Technology, Los Angeles The Swedish Office of Science and Technology, a Swedish Governmental Agency, is represented in strategic regions with significant development within science, technology and economic growth. The Swedish Office of Science and Technology monitors and conducts analysis in areas important to economic growth. It also initiates and supports collaboration between the Swedish and US government, academia and industry. Astragen LLC ASTRAGEN provides the scientific training and technological expertise to early- and mid-stage Biotech companies to efficiently and effectively transition from Preclinical development platforms to Clinical Trials/Clinical Research platforms. Our expertise is in the fields of ONCOLOGY, INFECTIOUS DISEASES, STEM CELL RESEARCH and GENOMICS. ASTRAGEN facilitates efficient integration of Preclinical Research with Clinical Research by organizing well-designed Clinical Trials Study Design, GCP training and streamlining the process of managing complex Clinical Trials during Phases I, II, III and IV. Source: Swedish-American Chamber of Commerce, San Francisco/Silicon Valley Press Release

Swiss voters back stem cell research under strict conditions

By Dr. Krishan Maggon, Pharma Biotech R&D Advisor, email: kmaggon@yahoo.com ICC- 20 route de Pre Bois, 1215 Geneva 15, Geneva, Switzerland Volume 5, December 2004-January 2005. In November 2004, voters in Switzerland by 66% majority, have strongly backed stem cell research under strict conditions. The Swiss parliament had passed the original law in 2003 but its application was challenged by a coalition of right wing religious conservatives (Catholic Church and Catholic Doctors, Evangelic, Medical Ethics, Pro-Life) and left wing greens, ecologists and socialists opposed to genetic engineering, globalization and big pharma. In French-speaking Switzerland the percentage was even higher. Geneva recorded the highest level of support at 84.5 per cent. Voter turnout was low at 35% (2 million votes cast) due to the complexity of the subject and 20% of the citizens stated in a poll that the subject was difficult to understand. The Swiss Government, parliament, research institutes and universities and pharmaceutical and biotechnology industry had urged support for stem cell research. The debate in Switzerland closely matched the heated exchanges in USA, California, Germany, Austria, UK and Sweden. Switzerland is a small landlocked country in the heart of Europe with a population of 7.2 million and has a system of direct democracy and frequent votation. The country is a leader in high technology, science and medical research and is home to major companies like Novartis, Roche, Serono, Nestle and international organizations like World Health Organization, International Red Cross, Center European Nuclear Research and International Olympic Committee. Swiss voters have backed research in science and medicine and have rejected outright bans in previous national votes. In the year 2000, 72% voters rejected a proposal banning in vitro fertilization and although the first voting on the first "delay for abortion" was rejected by 52% of voters in 1977, the law passed in 2002 where strict conditions were imposed for on demand abortions. Swiss voters have rejected outright ban on animal experimentation, first in 1985 by 70%, second in 1992 by 56% and once again in 1993 by 72%. The shift in voting percentage is reflective of masked language of the proposal. In 1998, a proposal to ban genetic engineering and manipulation was refused by 66% of voters. The present law dealing with stem cells was initially voted in 1992 by 74% of voters. Next year, a new law dealing with clinical research, tissue banks for donors and a proposal to ban all genetic modifications of living organisms for five years will be voted in a national poll. About 170,000 Swiss patients participate in global clinical trials of new medicines each year. The new legislation will permit research on stem cells from surplus human embryos under strict conditions. The production of stem cells will be limited to embryos not older than seven days. Therapeutic cloning and the trade in embryos will remain banned along with research on the embryos themselves. Informed consent of the couple using in vitro fertilization will be required for initiating any project; otherwise such embryos will be destroyed. Commercialization of the stem cells is not allowed and donors do not have any right to receive free products coming out of research. All projects using stem cells must provide scientific, ethical and medical rationale for research, advance our understanding of a serious medical condition/disease, exhaust all alternatives like using animal or adult cells, obtain the approval of the Institutional Ethical Review Committee, National Fund for Research and Federal Office for Public Health. The investigator will use the minimum number of stem cells and provide regular updates and progress report and any termination or final study reports to authorities and publish the results. For all exports or import of stem cells, the other country legal framework for stem cells should be similar to Switzerland. The Swiss stem-cell law falls between the liberal regulations in Britain, Sweden and Austria’s restrictive legislation. Three years ago Switzerland’s National Science Foundation gave its approval for research on stem cells imported from abroad. The present vote will allow about ten research groups to initiate stem cell research for therapeutic use. The interest in human stem cells is based on the fact that these cells offer the potential into development into any critical tissue or organ thereby providing novel therapy options. Stem cells offer a precious source of undifferentiated material for the study of cell maturation and specialization and are a potential source of material for the cure and replacement of damaged or declining organs and tissues. Stem cell lines with built in genetic diseases like diabetes, Parkinson’s and Alzheimer’s and with selective RNA interference for switching off genes can help us understand how genes trigger diseases. Before any medical or therapeutic use, knowledge about their growth and differentiation into tissues and organs is required. Application areas in cell replacement therapy and bone and tissue engineering for incurable and degenerative diseases (Alzheimer), osteoporosis, for cardiovascular diseases, for diseases of the nervous system (e.g. Parkinson, multiple sclerosis) and cancer (e.g. leukemia) get a major share of research efforts. Only one research group in University of Geneva is active with imported human embryonic stem cells for study of aging process since 2001. Swiss research groups at the Universities of Geneva, Basel and Zurich have published papers and were successful in growing and transforming animal stem cells into myocardium and neurons. It will take about a year for any research group to grow a stable stem cell line and the project cost estimate is about $100,000. The current worldwide market for stem cells is estimated to reach $12 billion in 2005 and $52 billion in 2010. * Please reference or credit any material, article or figure cited from http://www.medicineandbiotech.com as: Copyright 2004. MedicineandBiotech.com, http://www.medicineandbiotech.com/ Disclaimer: MedicineandBiotech.com is managed by AstraGen LLC. Please re-distribute this e-magazine. AstraGen LLC and MedicineandBiotech.com do not assume, and hereby disclaim, any liability for any loss or damage caused by errors or omissions in any material published at the web-site http://www.medicineandbiotech.com, whether such errors or omissions resulted from negligence, misstatements or other oversights.

Stem Cell Research in UK

August 11, 2004. For the first time, British scientists have been given permission to perform therapeutic cloning using human embryos. The Human Fertilisation and Embryology Authority granted the license to experts at the University of Newcastle. They are investigating new treatments for diabetes, Parkinson's and Alzheimer's disease. This decision could open a new era of research by scientists looking for remedies for diseases. The research will involve experts from the Institute of Human Genetics at Newcastle University, and the Newcastle Fertility Center. This is possibly the first time such a license has been granted in Europe, as well as in the UK. Therapeutic cloning has been legal in Britain since 2001. This license will be for at least five years - if not many more - before patients could receive stem cell treatments based on their work. Stem cell treatments are carried out for medical reasons. Even though the science is similar, this technique is different to reproductive cloning, which aims to create a human being. Cell nuclear replacement (CNR) or the cloning technique involves removing the nucleus of a human egg cell and replacing it with the nucleus from a human body cell, such as a skin cell. The egg is then artificially stimulated. This causes the egg to divide and behave in a similar way to a standard embryo fertilized by sperm. The eggs used in such studies are left over from IVF treatment. They are donated by couples, and would otherwise have been destroyed. Scientists from the Newcastle NHS Fertility Center say that since they submitted their application, they have had overwhelming support from senior scientists and clinicians from all over the world and many letters from patients who may benefit from the research. But Professor Murdoch at Newcastle NHS Fertility Center said: "Realistically, we have at least five years of further laboratory-based work to do before we move to clinical trials but this could be reduced if we receive additional funding which would allow us to increase the size of our team." "This research should give valuable insight into the development of many diseases." Suzi Leather, chair of the Human Fertilisation and Embryology Authority, said an initial one-year research license had been granted after "careful consideration of all the scientific, ethical, legal and medical aspects of the project". She said: "This is an important area of research and a responsible use of technology. "The HFEA is there to make sure any research involving human embryos is scrutinized and properly regulated." A spokeswoman for the British Medical Association said: "We support strong regulation so that therapeutic cloning to extract embryonic stem cells for life-saving treatment, which most of the public supports, can go ahead while human reproductive cloning, which most of the public opposes, cannot." But Julia Millington of the ProLife Party, said it planned to take advice over whether it could mount a legal challenge to the HFEA decision. Cloning human embryos for therapeutic purposes was made legal by an amendment to the Human Embryology Act in January 2001 in UK. But cloning humans for reproductive purposes remains illegal and is punishable by a 10-year prison sentence and unlimited fines in UK.

Intro to Stem Cell Research Stem cells provide an excellent model system to understand the differentiation, development and functioning of gonads, and further use of these cells in transplantation or cell-based therapies. Stem cells comprise a special kind of cell that has a unique capacity to renew itself and to give rise to specialized cell types. Stem cells may be able to replace cells & tissues that are damaged & diseased. Embryonic germ cells present a better source of pluripotent stem cells. The germ cells are specialized cells, which differentiate into sperm or oocytes. Spermatogonial stem cells are the only stem cells in the adult mammalian body that can be recognized and studied at cellular level with respect to proliferation and differentiation. Research on oogonial stem cells has recently been encouraged throughout the world due to the demand for oocytes for various research purposes. Mechanism of regulation of follicle formation, oocyte attrition and follicle development and atresia are only partially understood. Hence, the stages of development, its interaction with the neighboring somatic cells during each developmental stage and the molecular regulation underlying is under study. These studies may have numerous benefits and will also result in establishment of treatment of ovarian disorders, and in identifying cure for infertility that occurs due to ovarian pathophysiology. Research using stem cells has several applications in basic biology and clinical medicine. Recent advances in the establishment of male germ line stem cells provided researchers with the ability to identify, isolate, maintain, expand and differentiate the spermatogonia, the primitive male germ cells, as cell lines under in vitro conditions. The ability to culture and manipulate stem cell lines from male germ cells has allowed for research into spermatogenesis and male infertility, in a more advance manner than that facilitated by the use of somatic stem cells. After the introduction of exogenous genes, the spermatogonial cells can be transplanted into the seminiferous tubules of recipients, where the transplanted cells can contribute to the offspring. Currently, research is in progress to study the origin, life cycle and establishment of stem cell lines from male germ cells, as well as the current status of transplantation techniques and the application of spermatogonial stem cell lines. Stem cell technology is rapidly being developed and implemented in efforts to generate new organs that may be used to replace damaged or diseased organs, or to "rebuild" a partially damaged organ. Several laboratories have performed studies aimed at determining whether neural stem cell transplantation can result in functional recovery in experimental models of traumatic CNS injury and neurodegenerative disorders. For example, transplantation of embryonic stem cells into injured spinal cord promoted functional recovery (McDonald et al.), and transplantation of mesencephalic neural progenitor cells into hemiparkinsonian rats results in improved motor function (Studer et al). Another approach is to stimulate existing neural stem cells to proliferate and differentiate into neurons. It is now established that the adult human brain does contain pluripotent neural stem cells (Eriksson et al and Johansson et al). In the case of Alzheimer's disease, such neural stem cell-based approaches would most likely be applied to patients in the early stages of Alzheimer’s with the hope of replacing damaged neuronal circuits and thereby restoring learning and memory abilities. J.W. McDonald, X.Z. Liu, Y. Qu, S. Liu, S.K. Mickey, D. Turetsky, D.I. Gottlieb and D.W. Choi, Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nature Med. 5 (1999), pp. 1410–1412. L. Studer, V. Tabar and R.D. McKay, Transplantation of expanded mesencephalic precursors leads to recovery in Parkinsonian rats. Nat. Neurosci. 1 (1998), pp. 290–295. P.S. Eriksson, E. Perfilieva, T. Bjork-Eriksson, A.M. Alborn, C. Nordborg, D.A. Peterson and F.H. Gage, Neurogenesis in the adult human hippocampus. Nature Med. 4 (1998), pp. 1313–1317. Nora Carson, Ph.D.; Contributing Writer