A new thrombolytic treatment discovered in India is poised to enter clinical trials following local authorities' go-ahead on 17 August 2012. The home-grown clot-dissolving therapeutic could become the first innovative compound from an Indian public institute jointly developed with a US company. The drug, clot-specific streptokinase (CSSK), was developed by Girish Sahni and colleagues at the Institute of Microbial Technology in Chandigarh. In 2006, Nostrum Pharmaceuticals of Edison, New Jersey, bought the licensing rights to CSSK for $5 million plus royalties and now will progress the drug through phase 2 and 3 trials. Bacterial streptokinase, the original clot-busting agent, has been in use since the 1970s. In the early 1990s, South San Francisco, California–based Genentech introduced recombinant human tissue plasminogen activator (tPA), which proved only slightly superior to streptokinase. One advantage of Genentech's tPA, however, was its specificity, as tPA is activated only in the presence of fibrin in blood clots. Streptokinase, in contrast, is a nonspecific plasminogen activator. Its presence can generate plasmin throughout circulation, promoting the proteolytic degradation of blood factors and increasing the risk of hemorrhagic complications. The Indian group solved this specificity problem by modifying streptokinase, fusing its core elements with fibrin-binding domains 4 and 5 of human fibronectin. The resulting CSSK is a pro-drug that remains inactive in circulation until it meets a fibrin clot. The clot plasmin then snips off the fibrin-binding domains to activate plasminogen in a clot-specific way. Sahni says that studies in ex vivo human blood circulation and in vivo primate models (unpublished results) “clearly indicate a blood-clotting factors protection profile and specificity of action comparable, perhaps even superior, to tPA.” If CSSK is approved, it could be India's answer to more expensive thrombolytic agents such as tPA. “At about $800–$1,000 per dose, against $30–$50 for streptokinase, tPA is unaffordable for the general masses in the third world,” Sahni says. This translational strategy, whereby Indian intellectual property is commercialized by US companies, could be “a great role model” for future products. “Certainly a close industry-scientist-investor liaison will be highly desirable. This is perhaps one of the very few examples in India where original research has led to a potential globally important biotherapeutic,” says Govindarajan Padmanabhan, a leading biochemist at the Indian Institute of Science in Bangalore. “In India, industry needs hand-holding with government support to eventually make a product, at least in this area [of biologics].”

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