Proteins are key players in the biological processes that determine whether a person is sick or well. So not surprisingly, they form the basis for some of today’s most important and effective drugs. But in some ways, these large, complex biomolecules are far from being the perfect drugs: they’re chewed up in the stomach if taken by mouth, and many of them break down even when injected-severely limiting which proteins can be used. Now a number of biotech companies are reporting progress in designing smaller, more stable molecules that mimic the therapeutic action of proteins, opening the door to completely new drugs, and to the possibility of replacing some painful injections with equally effective pills.
In July, MetaPhore Pharmaceuticals of St. Louis announced the successful safety testing in humans of a “mimetic”-a drug that mimics the action of a human protein. The new drug is a copycat of a natural enzyme that disarms toxic free radicals, and it could eventually be used to treat cancer, arthritis, pain and even the aging process. But beyond all that, the drug demonstrates that a small engineered molecule can, in fact, take the place of a pharmaceutical protein.
Mimicking a protein was an accomplishment considered impossible just a decade ago, says Adrian Whitty, a senior scientist at Cambridge, MA, biotech giant Biogen. Only proteins, he explains, were thought capable of carrying out complex functions like, for example, triggering a chain of events inside a cell by binding to certain receptors on its surface. But in the mid-1990s, several groups showed that smaller molecules, initially found by random screening, could actually do the same job by binding to “hot spots” on those receptors. Since then, researchers have used either screening or computers to find or design more such targeted molecules, giving birth to mimetics.
A handful of companies have formed to tap mimetics’ potential. Locus Discovery, a Philadelphia-area startup, and Palo Alto, CA’s Affymax each say they have developed mimetics of erythropoietin, biotech’s best-selling protein-based drug, which helps reverse anemia caused by chemotherapy and kidney dialysis. Since erythropoietin must now be injected, a mimetic-based pill would be poised to capture its $6 billion market. If such pills can prove themselves in clinical trials, it could mark the end of painful injections for many patients.
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