NEWS OF TH E WEEK
PIRAMAL DROPS DRUG DISCOVERY PHARMACEUTICALS: Risks and regulations convince the Indian company to reallocate resources N A MOVE THAT RAISES QUESTIONS about the
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future of drug research in India, Piramal Enterprises will end its drug discovery activities. The decision— which involves possible job losses—will affect several hundred scientists, many of whom were recruited internationally to work in Mumbai in one of India’s most sophisticated pharmaceutical labs. The company has been considered an Indian leader in drug research since opening its discovery labs in 2004. Within the firm, drug discovery was championed by the vice chairman, Swati A. Piramal, a medical doctor who also holds a master’s degree from the Harvard School of Public Health. “After reevaluating the risk-benefits of new chemical entity research, the company decided to focus resources on our other areas of R&D with shorter development timeDANISH SIDD IQUI/REUTERS/NEWSCOM
A Piramal scientist at work in Mumbai last month.
Synthetic platelets (red, about 2 µm across) embedded in a fibrin network (blue) contribute to clot contraction, as shown here at the beginning (top) and end of a computational simulation.
SYNTHETIC PLATELETS BOOST CLOTTING
NAT. MATER.
MATERIALS SCIENCE: Deformable microgels mimic natural platelets
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LATELETS ARE specialized blood cells that par-
ticipate in the clotting process the body uses to stanch bleeding. A team of researchers at Georgia Tech led by chemist L. Andrew Lyon and biomedical engineer Thomas H. Barker has designed new synthetic platelets that have the potential to boost clotting when traumatic injury overwhelms the natural clotting process (Nat. Mater. 2014, DOI: 10.1038/nmat4066). The synthetic platelets are made of poly(N-isopropylacrylamide-co-acrylic acid) microgels with ultralow levels (< 0.5%) of cross-linking. Compared with previous synthetic platelets, they boost clotting specifically at injury sites without causing unwanted clotting elsewhere. That’s because each particle is studded with recognition motifs that bind fibrin, an insoluble protein that forms only after clotting has already started. “In principle, we can inject our particles and they can CEN.ACS.ORG
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lines and different risk profiles,” Piramal tells C&EN. Restrictions on conducting clinical trials in India played a role in the decision, made late last month, to end drug discovery, Piramal adds. “If Indian discoveries have to continue to undergo clinical trials in Western countries, there is a potential loss of the India advantage where drugs could be discovered and developed at a much lower cost than in the West,” she says. Piramal Enterprises is not ending all pharmaceutical R&D, Piramal insists. The company has several drug candidates undergoing trials in the U.S. and other countries. And it will still perform R&D in anesthesia, molecular imaging, phytomedicines, generic pharmaceutical ingredients, drug formulation, and over-thecounter products. The decision is not a serious setback for drug discovery in India, argues Nailesh A. Bhatt, managing director of Proximare, a life sciences consulting firm with offices in India and New Jersey. “It was a decision made by one company based on its own business plan and risk profile,” he says. “Companies like Glenmark Pharmaceuticals, Zydus Cadila, Biocon, and Suven Life Sciences continue to invest large resources in drug discovery.” Indeed, Suven remains committed to its central nervous system R&D, confirms CEO Venkat Jasti. “In new chemical entity research, failure is the norm and success is a rarity,” he says. “You need to be patient and not worry about market capitalization and pressure from the markets.”—JEAN-FRANÇOIS TREMBLAY
circulate freely in the bloodstream without causing any detrimental off-target effects,” says Ashley C. Brown, a research scientist working with Barker and Lyon. “Our trigger to augment clotting is more specific than previous synthetic platelets.” Another key feature of the new synthetic platelets is their ability to induce clot contraction, which is thought to help stabilize the clot and protect it from breaking down. This is a function of natural platelets that has not previously been seen in synthetic platelets. The researchers think these synthetic platelets can induce clot contraction because they are highly deformable, which permits more extensive engagement of the clot through the recognition motifs. That deformability is a direct result of the low level of cross-linking. “With the addition of even small amounts of cross-linker—2% cross-linking density—we inhibited clot contraction,” Brown says. The researchers injected the synthetic platelets into rats. Rats that received the synthetic platelets bled less when cut than rats that didn’t receive them. More data are needed on the biodistribution and clearance of the particles, says Erin Lavik, a biomedical engineer at Case Western Reserve University who is also working on synthetic platelets. “With inflexible particles, we’re limited in how large we can make them and get good clearance from uninjured tissues,” she says. “If these flexible ones avoid that issue, they could have significant application.”—CELIA ARNAUD
SEPTEMBER 15, 2014
