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Staking a claim
Since the advent of stem cell research, Big Pharma has shown an interest in leveraging its power for their research and development efforts—although the world's top pharmas have shown reluctance to take on the inherent risks involved with technology and knowledge that is still relatively young.
According to market research firm Frost & Sullivan, Big Pharma has been cautious in approaching stem cell research, but companies have accelerated their research presence and investment in stem cells since President Barack Obama lifted restrictions on government funding of human embryonic stem cell (hESC) projects. Since that time, there has been an increase in Big Pharma's efforts in this area, primarily in the way of drug screening and toxicity testing, says Frost & Sullivan.
"Big Pharma adopted a cautious role by engaging in strategic alliances to develop and commercialize stem cell-based products," says Frost & Sullivan analyst Sandhya Kamath. "Autologous stem cells, screening drugs with stem cells, induced pluripotent stem cells and stem cell lines are some areas where pharma is concentrating their efforts and submitting several patents."
Corporate venture funds of pharma companies have been supporting stem cell efforts from research institutes and companies, which could be with a strategic interest in using startup companies they fund for research collaboration or future mergers and acquisitions, adds Kamath.
While our coverage of companies involved in the stem cell market is by no means conclusive (and the companies are listed in no particular order), we are shining a light on some of the leaders in this field, as identified by Frost & Sullivan.
Company: Novartis AG
Location: Basel, Switzerland
Focus: Neuromuscular disorders
The Novartis Institutes for BioMedical Research (NIBR), the global pharmaceutical research organization for Novartis, says it is "committed to discovering innovative medicines that treat disease and improve human health." Much of the NIBR's work has focused on "pioneering a scientific approach that focuses on discovering and developing medicines for diseases with significant unmet medical needs for which the underlying mechanism of disease is known."
Much of the NIBR's work with stem cells has focused on the use of hESCs, while acknowledging that "our understanding of these cells is at an early stage; yet, they hold immense potential for combating diseases such as Parkinson's, Alzheimer's and diabetes."
With these concerns in mind, Novartis in 2002 established an ethics committee to assess preclinical research projects involving human embryos and hESCs in order to ensure compliance with the company's internal ethical guidelines. The committee is comprised of external, independent specialists to oversee the company's research efforts in the field of stem cell research and to advise Novartis' executive committee on all bioethical issues of relevance for the company.
"Novartis acknowledges that human embryonic stem cell research is an evolving field and one characterized by ethical complexities," the company says on its website. "The role of our ethics committee is to help us establish criteria and procedures which strike the right balance between freedom of research and the legitimate demands of society."
In November, Novartis announced that it will invest $1 billion over the next five years in its R&D efforts in China, including a "significant expansion" of its NIBR facilities in Shanghai.
The NIBR has ongoing research partnerships with academic centers, such as the Harvard Stem Cell Institute, and is focused on finding small molecules that affect neuromuscular disorders. Additionally, the institute is collaborating with a network of researchers, foundations and clinicians around spinal muscular atrophy (SMA) using SMA patient-derived stem cells.
"Induced pluripotent stem cells and motor neurons derived from those cells provide cellular models to study disease etiology and help to identify and validate new therapies," says Tewis Bouwmeester, executive director of developmental and molecular pathways at the NIBR.
Bouwmeester explains that SMA is caused by a single gene defect in the SMN1 gene, which produces the SMN protein, a lack of which leads to splicing errors. Some patients experience progressive paralysis caused by the loss of motor neurons in the spinal cord.
"Basic research tells us that motor neurons are dying because they lack SMN protein, a target that scientists might be able to drug, making the disease potentially treatable," says Bouwmeester. "There are various distinctive ways to possibly increase SMN levels, including prevention of protein degradation or changing the DNA sequence. Our approach is to search for molecules that increase functional SMN protein.
"Such new research insights could potentially lead to better understanding of other neurodegenerative diseases, such as Alzheimer's disease," Bouwmeester notes.
Location: Basel, Switzerland
Focus: Toxicology and drug development
Although stem cell research represents a small part of Roche's global R&D efforts, the company has several collaborations underway with outside partners involving toxicological and safety tests and screening in various human stem cell lines.
Kyle Kolaja, director and global head of predictive toxicology screens and investigative toxicology screens for Roche in the United States, says Roche's goal is to "improve drug development while reducing animal testing and potential serious adverse events in human trials."
"We provide external partners with compounds from our drug library for testing on hESCs," Kolaja says. "We think it is very meaningful to help identify compounds that will have a better safety profile and a lower-stage attrition. If we can identify and weed out bad-acting compounds and poor patient response, we can screen them out early. "
For example, Roche recently entered into a partnership with Cellular Dynamics International Inc. to test whether potential new drugs damage heart tissue using stem cells.
"We are looking for a better model of cardiotoxicity, " Kolaja says. "If you look at what's available even in a stem cell-derived model of the heart, they are either rodent-based or don't beat. A lot of them will undergo cell division. That doesn't happen in a normal heart. This slows it down to near or no proliferation rate. We can already see that this cell is behaving very differently. If you look at stem cell-derived cardiomyocytes, they beat at about 40 beats per minute and don't proliferate. That's a very high level."
In June, Roche announced an agreement to provide the latest- generation microarray systems, high-throughput screening instruments, genetic expression profilers and exome sequencing technologies to cancer researchers at UCLA. Roche also serves on the steering body of the U.K. consortium Stem Cells for Safer Medicines (SC4SM), and has ongoing collaborations with Harvard University, Massachusetts General Hospital and the Institute for Stem cell Therapy and Exploration of Monogenic Diseases (I-STEM) in Paris.
In addition to these external partnerships, Roche has commenced stem cell research in-house, including use of hESCs both as a discovery tool and as a potential therapeutic modality, with the goal to develop treatment strategies for incurable or inadequately treated severe disease such as central nervous system disorders. Roche has already started research and preclinical feasibility projects on the use of adult stem cells in other devastating diseases like lung fibrosis, and evaluates similar indications with high unmet medical need like renal failure or type 1 diabetes.
All of these efforts will lead Roche down a path to realizing the promise of personalized medicine—which has become a buzzword in the pharma realm in recent years, says Kolaja.
"To me, personalized medicine means getting the right dose of the right drug to the right patient at the right time," he says. "In doing so, this will link all of the arms of the Roche group together, from our diagnostic arm, to our applied science arm and to our pharma division."
Company: GlaxoSmithKline PLC (GSK)
Focus: Therapeutic agents; regenerative medicine
For U.K.-based GSK, stem cells are viewed as complementary to many of the pharma's drug discovery platforms. This means the industry could be able to test compounds in human cells instead of non-human cells, thereby improving the prediction of preclinical screens for efficacy and safety, a spokesman tells ddn.
"They have the notable advantage that potentially they can be used to produce multiple mature human cell types that previously were either impossible or difficult to obtain, such as neurons or cardiomyocytes," GSK says. "We are also excited about the manipulation of the naturally occurring stem cells within the body to increase their abilities to repair tissues, although this is a longer-term project."
Prioritization of this research depends on the goals of the R&D organization, GSK says.
"Stem cells provide novel opportunities that didn't previously exist—they could ultimately be beneficial to drug discovery in many ways, including as tools and targets for drug discovery and as new therapeutic agents," GSK 's spokesman says. "In the generation of tools, stem cells can be induced to generate specific human cell types for research and compound screening. It may also become possible to generate human cells of relevance to diseases, thereby improving the relevance of cell models to human diseases. As therapeutic targets, adult stem cells residing in multiple organs of the body could be modulated by therapeutic reagents to induce regeneration. For instance, in Alzheimer's disease, if a drug could be found that is able to induce the production of new neurons from neural stem cells, there is the potential of returning lost function. Finally, stem cells have the potential to be used as therapeutic agents. Stem cells and their progenies grown and manipulated outside the body might be introduced into the body for therapeutic purposes."
One of the pharma's most advanced clinical development programs, one being developed by GSK's Rare Diseases unit, is a stem cell gene therapy for severe combined immune deficiency (ADA-SCID), a rare and life-threatening immune deficiency disorder. Results from these clinical studies were published in 2009 in the New England Journal of Medicine.
GSK has allied with the Harvard Stem Cell Institute to develop new medicines, and with the Fondazione Telethon and Fondazione San Raffaele to research and develop novel treatments to address rare genetic disorders, using gene therapy carried out on stem cells taken from the patient's bone marrow. GSK is also a founding member of the Stem Cells for Safer Medicine (SC4SM) initiative in the United Kingdom, which brings together pharmaceutical companies and public-sector organizations.
Company: Pfizer Inc.
Location: New York
Focus: Drug screening
When people think of human embryonic stem cells, they don't often imagine the power of these cells in drug discovery, but Pfizer says it has been using animal or adult stem cells in its laboratories for more than a decade to help screen new compounds and identify safer and more effective medicines.
In 2009, Pfizer announced that it will invest $100 million into its international stem cell development program.
"Pfizer has begun to explore accessing drug development technology from leading academic, biotechnology or pharmaceutical partners around the world, who also have experience with currently available, human embryonic stem cell lines that meet the highest ethical standards set by leading scientific authorities," the company says on its website.
In April, Pfizer established a new biotech unit in Cambridge, the United Kingdom, that will combine research in pain, sensory disorders and regenerative medicine. Taking Pfizer's expertise in the field of sodium ion channels, Neusentis scientists will apply this knowledge to deliver new medicines across all forms of pain influenced by this mechanism, as well as a regenerative medicine portfolio. Neusentis is developing a cell-based therapy for age-related macular degeneration constituted by retinal-pigmented epithelium made in vitro from a continuously growing human pluripotent stem cell line. Pfizer and Neusentis initiated their first stem cell clinical study for patients with ulcerative colitis this year.
Some of Pfizer's external partners include the University College of London and the University of Wisconsin's Alumni Research Foundation.
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