But they're not easy to study. Where DNA has four building blocks and proteins, 20, complex sugars have 48. So a single five-unit
chain (out of the 150 or so different sorts found on the surface of a protein) might have more than 250 million different
combinations. Sugars routinely come in complex mixtures, and unlike, say, DNA, they can't be amplified to increase sample
size to make them easier to get at.
But in 1999, a team of Massachusetts Institute of Technology (MIT) biologists, chemists, and computer scientists defied conventional
wisdom, cobbling together a novel technology from their diverse toolkits. It's a three-part process of near-endless elimination.
Techniques using enzymes and other chemicals break down the sugar's myriad branches and chains into manageable sections. Hardware,
including mass spectrometry and nuclear magnetic resonance, turns its high-tech gaze on these sections, collecting, collating,
and refining data about it. Bioinformatics, mathematical modeling, and other software run all this information through the
system and spit out the solution—the complex sugar's unique structure and sequence. `
Now that the MITers had this breakthrough, what would they do it? The answer came in 2002 with the start up of Momenta Pharmaceuticals.
"I call our company an upside-down biotech," said Craig Wheeler, president and CEO. "We have our set of tools—our new lens
into biology—to understand these mixtures."
The company is operating on a three-part strategy, using its technology first to produce generics of complex drugs (its
initial product, a generic version of Sanofi-Aventis' Lovenox, a big-selling heparin-class drug used to prevent blood clots,
is expected to launch late this year or early next); then to improve on them (as the company is doing with a new, rationally
designed heparin); and finally to create new drugs (Momenta is currently working on a targeted sugar drug that slows tumor
growth and speeds cell death in cancers).
Banking as it is on follow-on biologics as the key to its short-term success, Momenta has followed the congressional debate
over legislation authorizing FDA to approve biosimilars. Wheeler has pow-wowed with agency officials to unlock the secrets
of the company's novel methodology, because it has unique tools to establish bioequivalence and other criteria. If all goes
to plan, Momenta could do a kind of end run around the knotty debates over validation, efficacy, and safety of biogenerics.
Wheeler proposes to verify his products through cheap, quick chemical analysis rather than expensive, lengthy clinical trials.
If he's right, Momenta can rev up the engine and start plucking the high-hanging fruit. –WALTER ARMSTRONG
NO RAIN ON RNAi PARADE
It's still a few years before RNAi sizzles onto the scene, but biotechs and Big Pharma are placing their bets on these nucleotides
William Shakespeare first penned the advice, "Don't shoot the messenger." But today, pharma companies are aiming their guns
to do just that and, in the process, to bring about a new way to conquer many complex diseases.
Messenger RNA, or mRNA, is the first step in translating DNA into proteins. mRNA brings genetic information to the rRNA (ribosomal
RNA) complex, which forms the amino acid chains that make up proteins. These proteins are then responsible for carrying out
everyday cellular processes, like converting glucose into energy.
Drugmakers seek to mimic the bodys natural RNAi process to stop disease. Researchers inject double-stranded RNA into cells,
where it bonds with the bodys silencing complex. It then attaches to target mRNA strands and destroys them.