Zelos Therapeutics (www.zelostherapeutics.com) is developing a novel peptide analog of the parathyroid hormone (PTH) for postmenopausal osteoporosis, called Ostabolin-C (in Phase II trial).

PTH has two important signaling domains, the first domain activates adenylate cyclase, and the second domain stimulates protein kinase C activity. Studies invitro and animal models revealed that the adenylate cyclase signaling component was responsible for the bone-stimulating activity of PTH. We realized that modulating adenylate cyclase had important implications for osteoporosis therapy, says Paul Morley, Ph.D., scientific founder and CSO of Zelos Therapeutics.

Ostabolin-C activates bone-stimulation mechanisms, but does not affect bone resorption activity. Bone resorption leads to the side effects observed with existing injectable PTH drugs. Also, these injectables are more effective at reducing vertebral fractures than fractures of the hip or wrist. We anticipate that our peptide drug will have a lower incidence and severity of side effects and induce the formation of better quality bone at all of these sites, says Dr. Morley. Zelos has partnered with Nektar (www.nektar.com) to develop a pulmonary delivery formulation of Ostabolin-C.

We do not just mean business as profit only; instead we have a personal rapport with all our prospective clients. We believe in long term relationships. In fact it is our lasting relationships with our clients, both at professional as well as personal level that has served as a firm foundation for our company. We work for our clients, and measure our success by their success

Ambryx Biotechnology (www.ambryxbiotech.com) performs systematic screening of naturally derived peptides. It has an anticancer peptide in the preclinical stage with three more in R&D. We assessed secreted protein fractions derived from embryonic cells for apoptotic effects in multiple in vitro cancer cell models. We discovered a native protein that binds to zinc resulting in a conformation change revealing active peptide domains that have anticancer activity. We subsequently isolated the active peptide domain, says Helen Chen, Ph.D., VP of business development at Ambryx.

Ambryx anticancer peptide drug has natural glycosylation, so it has the potential to last longer in vivo and be truly bioavailable. The peptide was 8 to 10 times more active than native protein as it does not require zinc for activity, says Dr. Chen. The company is currently gathering data in animal obesity models.

Peptides play an important role in modulating many physiological processes in our body. Some of the benefits of working with peptides are: they are small, easily optimized, and can be quickly investigated for therapeutic potential. However, the field of peptide drug discovery was hampered by their high manufacturing costs, short half-life, and limited in vivo bioavailability. All that is changing now. Waheed Danho, Ph.D., distinguished research leader at Hoffmann-La Roche (www.roche.com) says, “Advancements in peptide manufacturing and improvements in peptide drug delivery systems have re-energized this field”. It is now easier to screen a large number of targets with peptides and eliminate the unpromising ones early on in the discovery process. Rational drug design, an informed approach to drug discovery, is the preferred route for Roche, which has a fully integrated peptide research program based on rational drug design. The quick-acting nature of peptides is often a disadvantage in many disease conditions. We perform extensive structure-activity-relationship studies to define peptide hot spots and use this information to design more potent, more specific, and more long-acting peptides, explains Dr. Danho.

A new report from PricewaterhouseCoopers (PwC) reveals that the Asia pharmaceutical industry is gearing up to be at the center of the global market and most pharmaceutical companies in the region expect this shift to happen fast. Fifty eight per cent of companies believe that the center of gravity of the global pharmaceutical market will be in Asia rather than North America and Europe in the near future.

The report, Gearing up for a Global Gravity Shift, is based on in-depth interviews with 185 senior pharmaceutical executives across nine different territories in the region; China, India, Malaysia, Philippines, Singapore, South Korea, Taiwan, Thailand and Vietnam.

The rise of Asia pharmaceutical industry :
Growth is top of the agenda for many companies with domestic companies seeking to go global and MNCs extending their presence in the region. Sixty five per cent of domestic companies report that increased global market share is important for their companies. A third of MNCs have immediate 12-month plans to further expand within the region through acquisitions or developing their own Greenfield sites.
?Not surprisingly, China and India head the list of target countries for expansion, with Singapore and South Korea next in the sights of MNCs, said Mr Matthew Wyborn, Asia Pacific Advisory Leader of PricewaterhouseCoopers.

Mr Abhijit Ghosh, Pharmaceutical and Healthcare Leader at PricewaterhouseCoopers Singapore, added, Singapore is poised to become one of the leading countries in the Asian pharmaceutical space. Its growth as a base for pharmaceutical activities is boosted by the country’s Intellectual Property Right (IPR) protection record and pro-active government policy which aims to develop the biomedical science cluster as one of the key pillars of the economy.

Mr Matthew Wyborn continued, MNCs are increasingly interested in setting up more research and development (R&D) facilities and conducting more clinical trials in certain Asia territories. At the same time, region-based pharmaceutical companies are seeking to expand their geographical footprint and become pan-regional or global players.

Over a third (34 percent) of domestic companies is looking to acquire pharmaceutical companies. More than half (52 percent) of these companies are seeking to acquire international market share. At present, fewer than half (45 percent) of the domestic companies surveyed had an international presence but international growth is high on their agenda.

A thirst for funding  :
Capital constraints can be a significant brake on growth for domestic pharmaceutical companies. Around half of all the domestic pharmaceutical companies surveyed in the region might be looking for deals if funding obstacles could be overcome. There are few specialized venture capital funds to support start-up biopharmaceutical companies in Asia. These companies do not have access to a supportive stock market environment, such as in a junior market like London’s Alternative Investment Market (AIM). While domestic pharmaceutical companies in the region are hungry for investment, particularly for R&D, just over a third (36 percent) of them would consider selling all or part of their company to foreign investors to raise funds. Many are also looking towards IPOs as a fundraising route; with 36 percent having plans to raise capital from foreign capital markets.

Risk reduction :
Both MNCs and domestic companies report progress towards risk reduction in the region. Three quarters (74 percent) of MNCs and 79 percent of domestic companies say they have seen improvement in IPR protection in the past five years, primarily as a result of the introduction of new IP laws underpinned by a stronger government emphasis on IPR protection and more rigorous applications of existing laws.

A changing pharmaceutical business model :
Competition from generics and pricing pressures in the healthcare market continue to create pressures for reduction in costs in all parts of the pharmaceutical value chain. Outsourcing to lower cost but highly effective companies in Asia has become a common response to these pressures. A majority of companies thought that most of the industry still does not see outsourcing in a sufficiently dynamic way and is missing opportunities for shared development, learning and improvement. So far, much of the focus has been on outsourcing drug manufacturing but increasingly, companies are turning their attention to R&D and clinical trials.

Mr Abhijit Ghosh said, As the industry moves to this future model, strategic partnerships or long-term partnerships are the preferred route, favored by 82 percent of the multinational pharmaceutical companies we surveyed who outsource.

Looking ahead, the pharmaceutical landscape for both MNCs and domestic companies alike in Asia will look radically different in the medium term, the report said. Companies that are outsourcing in the right way, at the right pace look set to get ahead of the game.

It’s amazing to us. We thought the cell was so simple, said Shu Chien, the senior author of the BBRC paper and a professor of bioengineering at UCSD’s Jacobs School of Engineering. But it’s really very complex and I’m not sure we’re covering much as yet. We certainly don’t know all the interactions among these molecules that bring the cell into action.

Examining living cells through a microscope, Chien and the paper’s co-author, associate project scientist Ying-Li Hu, filmed red-fluorescence-tagged paxillin molecules traveling from cell’s outer membrane along green-fluorescence-labeled traces of cytoskeleton. Even without video evidence, scientists have confirmed over the past 10 years that higher organisms use paxillin as a transmitter of locomotion and gene-expression signals from several classes of growth-factor receptors to the nucleus.

Cancer researchers are eager to understand paxillin’s many interactions because their malfunctions have been linked to a variety of cancers, tumor metastasis, and other disease processes. Tumor-causing versions of signaling molecules may attach to paxillin and disturb the normal adhesion and growth factor signaling steps required for controlled proliferation and cell growth. For example, human papilloma virus, which can cause cervical cancer, makes a protein that binds to paxillin and that interaction may contribute to the carcinogenic potential of the sexually transmitted virus.

Chien and Hu obtained cells for their most recent study from the inner membranous lining of a cow aorta. They added genetically engineered proteins tagged with red and green fluorescence markers to the bovine aortic endothelial cells, grew them in tissue culture, and filmed them while they passed fluid across the cell’s surface in a simulation of flowing blood. With that physical stimulus, paxillin consistently moved in the same direction as the fluid flow.

Paxillin is found primarily at focal adhesions, busy intersections of activity scattered around the cell’s cytoplasmic membrane. Focal adhesions are regions rich with receptors for growth factors and they are also structural attachment points that link the extracellular world to the protein filaments and tubes that comprise a cell’s internal cytoskeleton.

While researchers showed that paxillin serves as a docking station for a variety of signaling and structural proteins, they have been limited to visualizing paxillin with dyes that stain cells rigidly attached to microscope slides. Those snapshots of fixed cells can’t reveal paxillin movement.

We can now see the dynamics of how paxillin and other proteins move inside the cell with new fluorescent labels and live-cell video microscopy, said Chien, director of the Whitaker Institute of Biomedical Engineering at the Jacobs School.

The two-color labeling technique of Chien and Hu revealed that red-labeled paxillin is linked to green-labeled actin filaments, the thinnest of three types of protein filaments that make up the cytoskeleton of cells of higher organisms. Paxillin either slides along the actin filaments or is pulled by them. In a surprise, Chien and Hu also showed that paxillin itself forms long, fibrous structures in the cell cytoplasm. When actin is chemically removed, paxillin no longer moves and its fibrous structures disappear.

As least by showing that paxillin and actin filaments move together we have some insight into the possibility of how paxillin can transmit information from one region of the cell, such as the periphery, to another region of the cell, such as the nucleus, said Chien. The whole situation is much more complex than we have been able to show.

Chien, Hu, and their colleagues at UCSD had previously reported that paxillin can be rapidly assembled and disassembled, and they hypothesize that this process enables cell migration by assembling new focal adhesion sites in the direction of cell movement and disassembling them on the trailing side of the cell. Researchers are applying the fluorescence-labeling technique to the many other signaling and structural proteins found predominantly at focal adhesions.

When we piece all of these things together we can get a more complete understanding of how the cell functions, both in migration and signal transduction, said Chien. If we can understand the details of these processes, we can not only understand how normal cells function, but we can also look at diseased cells to see why they sometimes don’t move properly or why they don’t transmit information properly.

Video available at http://video-jsoe.ucsd.edu/asx/Paxillin.paper.wmv.asx.

An industry is considered to have arrived when allied businesses begin picking up steam. At the biotech capital of India, Bangalore, the country premier biotech show is on and among the announcements made is the low-key launch of BioPortEurope.

BioPortEurope is a one-stop-shop solution to facilitate Indian life sciences companies’ entry into the European market. Considering that India’s biotech industry has touched the $2 billion mark and is slated to grow at a fast pace, the service is timely and much needed, what with a number of Indian companies aspiring to enter the global markets.

BioPortEurope provides access to a mature network of experienced life sciences professionals in The Netherlands and in the EU member states including France, Switzerland, Germany, Spain, UK, Italy, Austria and Spain via its headquarters in Amsterdam. The service is available across the areas of pharmaceuticals, generics, vaccines, diagnostics, OTC & natural products, fine chemicals and technologies.

We are business catalysts for the industry, providing services that range from market assessments to distribution, said Dr Maarten Van Dongen. He represents InnoTact Consulting, the company that has launched the concept of BioPortEurope in India. Dr Maarten is currently in the process of scouting for an office space in India. InnoTact Consulting is likely to open office in Bangalore.

]]> http://www.bioconceptlabs.com/2010/03/09/bangalore-bio-bioporteurope-makes-access-to-eu-markets-easy/feed/ 0 http://www.bioconceptlabs.com/2010/03/09/loss-of-stem-cells-correlates-with-premature-aging-in-animal/ http://www.bioconceptlabs.com/2010/03/09/loss-of-stem-cells-correlates-with-premature-aging-in-animal/#comments Tue, 09 Mar 2010 10:52:50 +0000 admin http://www.bioconceptlabs.com/?p=97 Loss of Stem Cells Correlates with Premature Aging in Animal Study, Penn Researchers Find

Researchers at the Abramson Family Cancer Research Institute of the University of Pennsylvania have found that deleting a gene important in embryo development leads to premature aging and loss of stem cell reservoirs in adult mice. This gene, ATR, is essential for the body’s response to damaged DNA, and mutations in proteins in the DNA damage response underlie certain types of cancer and other disorders in humans. This work appears in the inaugural issue of Cell Stem Cell.

The reason these mice age prematurely is that we’re exhausting their ability to renew tissues, says Eric J. Brown, PhD, Assistant Professor of Cancer Biology. These findings may be helpful to the aging and oncology fields since premature aging syndromes and many cancers involve the loss of DNA repair genes.

When the researchers deleted ATR in the tissues of adult mice, they noticed that the mice showed signs of premature aging, such as hair graying, hair loss, and osteoporosis, within three to four months.

To be able to renew itself, most tissues have a reservoir of specific adult stem cells. These stem cells don’t divide as frequently as other cell types since they need to maintain the integrity of their DNA, and multiple divisions lead to natural breaks in DNA. But when these stem cells are needed, their progeny can rapidly divide and are able to replenish the tissue with new cells.

Brown explains that in the current study the mouse cells without ATR had an overwhelming amount of DNA damage and could not contribute to tissue renewal; nevertheless, the 10 to 20 percent of cells that escaped ATR deletion were able to reconstitute tissues in the engineered mice, at least initially. However, it appears that in the long run, even these cells were insufficient to maintain tissue integrity.

Think of aging as a slow loss of stem cells, a deterioration of pools of cells that reside in each tissue type, says Brown. We accelerated the aging process by wiping out a large fraction of these cells prematurely, in one fell swoop. Essentially, ATR-deleted mice start their young adulthood with two strikes against them in terms of long-term tissue maintenance, and so, they subsequently age before their time.

With this new knowledge of how DNA repair, stem cells, and the aging process interconnect, Brown, first author Yaroslava Ruzankina, and Amma Asare are currently using this mouse model to discover compounds that preserve stem cells and may, consequentially, suppress aging.

This work was funded in part by the National Institute on Aging, the Abramson Family Cancer Research Institute, and the General Motors Cancer Research Scholars Program. Co-authors in addition to Brown are Ruzankina, Asare, Carolina Pinzon-Guzman, Tony Ong, Laura Pontano, George Cotsarelis, Valerie Zediak, Marielena Velez, and Avinash Bhandoola, all from Penn.

The Department of Biotechnology (DBT), Ministry of Science & Technology, Government of India and the International AIDS Vaccine Initiative (IAVI) have signed an agreement to address a major obstacle in AIDS vaccine development: the design of candidate vaccines to elicit neutralizing antibodies against HIV.

A new Indian Medicinal Chemistry Program, co-sponsored and co-funded by IAVI and the Department of Biotechnology, will comprise top Indian and US scientists tasked with accelerating the pace of AIDS vaccine discovery and developing creative concepts for the next generation of AIDS vaccines.

IAVI Board Member and Union Minister for Science & Technology and Earth Sciences, Mr Kapil Sibal said, Vaccine research is so critical that the Health Ministry and the Science and Technology Ministry have joined hands to provide the effort the support it needs.?

The first component of the DBT IAVI Program will consist of a collaboration of principal investigators from different academic research laboratories to design novel HIV antigens. The investigators include Professor Virander S Chauhan of the International Centre for Genetic Engineering and Biotechnology, New Delhi; Professor Raghavan Varadarajan of the Indian Institute of Science, Bangalore; Dr Stephen Kaminsky of IAVI’s AIDS Vaccine Development Laboratory, New York; and Dr Philip Dawson of The Scripps Research Institute, California. IAVI and DBT may select additional principal investigators, contract researchers, or partners in India to participate in the Program, and will discuss ways to build infrastructure for subsequent HIV/AIDS vaccine candidate evaluation.

At a later stage, based on their initial research and vaccine design concepts, both partners expect to work with an Indian manufacturer to assist with high throughput synthesis, antigen chemical characterization and potency evaluation of proposed AIDS vaccine candidates.

This new partnership will broaden ongoing efforts in India to find an AIDS vaccine, said Mr Seth Berkley, CEO and President of IAVI. ?With our long-term Indian collaborators, the Ministry of Health and Family Welfare through the National AIDS Control Organization and the Indian Council of Medical Research, IAVI has successfully conducted two phase I clinical trials in the country. Through this new agreement, we will continue to tap some of the best minds in biotechnology to create new paradigms for AIDS vaccine design.

India’s Department of Biotechnology is delighted to be a part of the global search for an efficacious AIDS vaccine, stated Professor Maharaj K Bhan, Secretary, DBT. Only through these kinds of biotechnology ventures, involving international collaborations and the sharing of scientific knowledge, can we hope to solve the complex biomedical problems of our times.

The Indian Program will complement the work of IAVI’s Neutralizing Antibody Consortium (NAC), a team of internationally recognized scientists working on the neutralizing antibody challenge. Researchers believe an ideal AIDS vaccine must evoke an antibody response that can block HIV from entering healthy cells, as well as reduce the amount of viral dissemination through a cell-mediated immune response to HIV-infected cells. However, today, virtually all the current vaccine candidates in the pipeline are based on cell-mediated immune responses alone, failing to target the second critical arm of the human immune system.

“DBT brings enormous strengths in peptide and protein design to this collaboration with IAVI,” said Dr Dennis Burton, Scientific Director of the NAC. “We believe these strengths are crucial to the rational HIV vaccine design strategy being pursued by the Neutralizing Antibody Consortium.”