Pharmacy News: Purdue University Researcher’s Technology “Listens” to Cancer Cells, Shows Effects of Drug Therapies

Purdue University Researcher’s Technology “Listens” to Cancer Cells, Shows Effects of Drug Therapies

A Purdue physicist has created technology to detect motion inside three-dimensional tumor spheroids, which may enhance the pharmaceutical industry’s early drug discovery capabilities.

David Nolte has developed Holographic Tissue Dynamics Spectroscopy, a technology that allows researchers to look inside cells using holography and lasers. The technology was highlighted in a letter in the peer-reviewed Journal of Biomedical Optics. The work is done in collaboration with John Turek, professor of basic medical sciences at Purdue.

“This technique measures living motion inside a cell,” Nolte said. “We’re picking up all the activity and seeing how the cell modifies its activities in response to applied drugs.”

The first process used by Nolte’s technology is holography, which shows tumor tissue in three dimensions.

“We make digital holograms of thetumor, which can grow up to one millimeter,” Nolte said. “This holographic technique using lasers lets us see all the way through the tumor, not just the surface.”

The tissue dynamics spectroscopy used in Nolte’s technology creates an image that shows changes taking place inside cells.

“After making the hologram, we use spectroscopy to measure the time-dependent changes in the hologram,” Nolte said. “Fluctuation spectroscopy breaks down the changes into different frequencies, and we can tell how a cell’s membranes, mitochondria, nucleus and even cell division respond to drugs. We measure the frequency of light fluctuations as a function of time after a drug is applied.”

The resulting colorful frequency-versus-time spectrogram represents a unique voice-print of the drug used on the cells.

“Individual drugs have different spectrograms, but with similarities within specific classes,” Nolte said. “By looking at how cell motion responds to drugs, we can differentiate very fine mechanistic points between them.”

Drug researchers and manufacturers may benefit from the technology by being able to more quickly determine which drug candidates are most effective in battling tumors and other tissue diseases.

“This technology, with its high-throughput aspect, allows manufacturers to place a different tumor into 384 plates, test 384 different drug compounds and create 384 spectrograms in six hours,” Nolte said.

The State of Life Science Research

R&D Magazine asked research leaders from three life science industry sectors—big pharma, medical devices, and independent research organizations—to discuss the present and the future of life science.

Q: Tell us about some of the recent important research/developments at your organization.

Ven Manda, vice president MDT Ventures and New Therapies at Medtronic, Inc.: We are at a moment of convergence in medicine and technology with immense opportunities. At Medtronic, we specialize in an array of high-tech solutions—examples include resynchronization therapy for specific heart failure patients, neurostimulation for specific Parkinson’s patients; devices and therapies for spinal procedures; continuous glucose monitoring for diabetic patients; novel therapies for atrial fibrillation and valvular heart disease; and many others. These core technologies, combined with several emerging and innovative new therapies, including integrated biologic/drug delivery technologies for these and other chronic conditions, position us well for the future. Coupled with expanding infrastructure of enabling technologies, such as wireless systems, electronic medical records and our own strong history of developing sensors and diagnostic technologies to improve care, we envision a unique place for Medtronic at the epicenter of this ongoing change in health care delivery and meeting the needs of patients, doctors, and health care providers globally.

Dr. Marc Bonnefoi, deputy head, U.S. Research & Development for sanofi-aventis, Bridgewater, N.J.: Transforming R&D and fostering increased innovation is the first pillar of our group’s strategy and core to our commitment to provide hope and solutions to the potential 6.8 billion people in need. A new R&D model has been implemented to strengthen creativity and innovation while being centered on patients’ needs. It focuses on openness of our research teams towards large public research institutes, biotechs, and other external partners and on the creation of more flexible entrepreneurial units that foster the emergence of innovation. Through these partnerships, our goal is to advance scientific knowledge in areas that will have direct impact on providing patients with healthcare solutions that address unmet medical needs. By creating entrepreneurial units such as Aging, for example, we take the perspective of the patients to design our strategy. Our new Business Divisions in diabetes, oncology, and ophthalmology represent our strong and sustainable commitment in this area.

Kristina Vuori, President, Sanford-Burnham Medical Research Institute, and Director of Sanford-Burnham’s National Cancer Institute-designated Cancer Center One of our primary missions is to come up with scientific discoveries, and we probably do that on an almost daily basis. Out of all of these highlights for 2010, one major discovery that a Sanford-Burnham scientist, Erkki Ruoslahti, has made is that he has found a peptide, which is a small chain of amino acids or a protein, that can recognize and penetrate tumor tissues, and deliver therapeutics deep inside the tumor without affecting normal tissues.

One of the major breakthroughs for us as a scientific organization is that at the end of 2010 we announced two major partnering deals with pharmaceutical companies: Takeda and Johnson & Johnson. These are truly collaborative efforts where our scientists with the help of our chemical genomics center will team up with pharmaceutical companies and work together in moving our scientific laboratory discoveries forward for human benefit. This represents a big milestone in how we would like to do business in the future.

Q2) What impact has the poor economy had on the medical device market?

Manda: Clearly, 2010 was a challenging year for the entire medical device sector, and, in fact, the overall healthcare sector. However, we have seen sequential momentum in out key businesses, especially in emerging markets and in new business segments. Our diverse therapeutic and geographic portfolio serves us well at a time where the global economy is not yet on stable footing. Because our technology solutions primarily serve patients with moderate-to-advanced chronic disease (as in heart failure, CV disease, diabetes, etc.), the demand for our therapies worldwide far outstrips current penetration levels.

Q2) How has your research investment strategy been affected by recent economic changes?

Bonnefoi: Sanofi-aventis continues to focus on delivering therapies to patients that provide value to patients as well as payers and providers. As a percent of sale, our investment in R&D has not changed significantly.

Vuori: About 80% of our budget in La Jolla (Calif.) comes from the National Institutes of Health (NIH). Institute-wide, about 67% to 70% of our budget is from government sources. In Florida, we have a significant state funding component, so in Florida we are a little less dependent on government funding, but it’s very fair to say we live and die based on where the NIH’s budget is.

There are two things we have looked at with the reality that the government’s funding is very unlikely to increase in near future. One of them, of course, is how we can be more competitive for government grants and contracts. We continue to invest in high-end technologies that move our science forward within our organization. We provide seed funding and catalyze collaborative efforts where scientists team up to do science, seeking opportunities where complementary skills can be brought to bear. NIH’s funding for collaborative efforts in has been very favorable for us. We have been very competitive in getting large, team-based government grants.

The other reality for us is to diversify our revenue portfolio and be less dependent on NIH funding. We are seeking opportunities for funding from government agencies outside NIH, for example, the Department of Defense, which has medical research programs. We are increasingly paying attention to those, and, certainly continuing to expand our business transfer programs and continuing our efforts to bring in funding outside of government.

Q3)Have recent government policy changes affected the way your company does research or develop products? If so, please tell us how.

Manda: As requirements from regulatory bodies in various parts of the world evolve, we acknowledge and have felt the impact on our product development and approval timelines. That said, our experience and commitment to what we do best—providing high-tech, specialized solutions for patients with specific, advancing diseases—is grounded in conducting solid clinical trials and establishing the clinical evidence for appropriate use of our therapies. We are extremely well positioned to work with government agencies and support policy that ultimately enables innovation to accelerate and patients to receive the best set of choices that they can for their care. The case for accelerated and novel breakthrough concepts has never been stronger.

Bonnefoi: Our research continues to be focused on delivering healthcare solutions that address unmet medical needs to patients around the world. Recent government policy changes have not impacted this commitment.

Vuori: There hasn’t been much affect at this specific time. Obviously, we are looking very closely as to where the current challenges are to federally-funded embryonic stem cell research. At the present time, federal funding is allowable for stem cell research. We, of course, hope that viewpoint will prevail and continue. Other than that, I don’t think there have been big policy changes at the federal government level that have affected us.

Q4) Tell us about your organization’s notable research collaborations or new business opportunities that have taken place outside of the U.S.

Manda: We continue to determine how we best meet the unique need of patients and health-care delivery systems around the world. Clearly, no one country has a monopoly on innovation, therefore, it is imperative we take advantage of our global presence, strong depth of understanding of basic and applied research, product development, and efficient manufacturing and distribution systems to serve this increasing global demand for health care.

At present, 41% of our revenue comes from outside the U.S. We expect, in the next five years, that about 20% of our revenue will come from emerging markets specifically. We are very excited about our international business and the global collaborations we have embarked on, as important elements of our future growth.

Bonnefoi: Emerging markets are one of the growth pillars of sanofi-aventis. We have a well-established presence in emerging markets with activities in over 100 countries, including local manufacturing capabilities and clinical development units as well as a broad product portfolio adapted to local needs.

Within R&D, we have benefited from this global presence through the formation of partnerships and alliances with universities, research institutes, and biotechs throughout Europe and Asia. For example, we have a strategic research agreement with Shanghai Institutes for Biological Sciences (SIBS) that focuses on identifying innovative drugs for the treatment of neurological diseases, diabetes and cancer while also strengthening our R&D presence in China. We are also members of several academic consortia in Europe, including AVIESAN (French Life Sciences and Healthcare Alliance) and the Innovative Medicines Initiative (European public-private partnership). These partnerships aim to enhance scientific knowledge in the areas of life sciences and healthcare and to develop projects benefiting patients in research areas like immuno-inflammatory diseases, infectious diseases, and regenerative medicine. The partnerships also foster a spirit of collaboration and exchange between public and pharmaceutical industry researchers.

Finally, one of the entrepreneurial unit of our new R&D organization is entirely dedicated to Asia-Pacific.

Vuori: At a grass roots or individual investigator level, we have always been collaborative both nationally and internationally. Out of our some 800 scientists, a significant portion–some 30% to 40%–come from outside the United States and some 40 nationalities are represented here, so international collaboration comes naturally to our scientists. At the institute-wide level, I had mentioned the pharmaceutical arrangement made at the end of last year with the pharmaceutical company called Takeda, which is the largest pharmaceutical company in Japan. We seek larger technology transfer opportunities within the U.S. and outside in a manner consistent with the Bayh-Dole Act, since we receive a lot of NIH funding. We see a lot of opportunities to expand further our activities overseas and like many other organizations are thinking about opportunities in Asia and China.

Q5) What do you see as the next big breakthrough in life science and the medical device industry?

Manda: One of the great things about Medtronic is the opportunity to pursue the latest technical developments in medicine and access to the newest thinking about how to address significant, unmet clinical risk for a variety of medical conditions. In addition to a robust R&D pipeline, we have carved out a separate $100 million annual internal “venture” fund which allows us to incubate, test and accelerate novel, internal R&D concepts for diagnosis, monitoring, or treating a disease—concepts that may not necessarily fit into one of our existing businesses, but, if successful, can significantly advance standard-of-care for specific conditions, deliver long-term growth for the company, and enable new businesses to emerge.

Indeed this was the basis for several of our organically generated $1 billion product-lines such as cardiac resynchronization therapy. In addition to this “internal” fund, we also have a very active early-stage investment portfolio of more than 60 companies which gives us a first look at promising emerging technologies.

Our strong balance sheet allows us to invest in tuck-in acquisitions to get into new therapeutic areas and add adjacencies to our existing portfolio.

While it may be difficult to predict where the next “big thing” is going to come from, we are confident that Medtronic’s ability to invest in early and late-stage R&D concepts will allow us to lead the way in bringing breakthrough innovation to our customers.

Bonnefoi: With the explosion of genomics leading to knowledge of potential targets and mechanisms, we should increasingly have the ability to develop targeted therapies and get the right therapy to the right patient at the right time. However, the promise of translational medicine has not borne fruit yet to the extent that many expected. We believe this is due in part to an incomplete understanding of human diseases. We are seeking better and quicker ways to obtain human validation of our hypothesis. In addition, we have reoriented to focus on targeted therapies, viewing the needs of a patient and developing services and devices that help them manage the diseases.

Vuori: I suspect that many people would hope that the next breakthrough will come from our collective capability to leverage the knowledge that can be obtained from the human genome sequence. The blueprint for life has been uncovered, if you will. Collectively, I don’t think scientists have put that knowledge to very good use yet, but I do expect the breakthrough will come from understanding the difference between a healthy and diseased human genome, and how those changes can be detected. This is probably a key for coming up with the concept of personalized medicine, in which we can tailor disease diagnosis, prognosis, and treatment based on the information the individual will have in his or her genome and epigenome. I think at Sanford-Burnham what we are very decisively doing is taking this knowledge of the human genome, understanding how the genes and their products—the proteins—work with them, and trying to come up with the chemical tools and chemical compounds that can be used for two things: one, to further the laboratory use of those compounds to study and understand what the genes and products are doing and their association with various diseases; and, two, to find a way that these chemical compounds can serve as prototypes of medicines.