Find the Bad Protein; Then, Fix It

By Lisa Takeuchi Cullen

The implications were chilling. Since the mid-1990s, the words mad-cow disease had turned beef eaters around the world to tofu tasters as people began to die of the human variant of the disease. Then in 2004 came another disturbing report in the medical journal the Lancet: variant Creutzfeldt-Jakob disease (VCJD), as the illness is properly called, could be spread through blood transfusions. With no way to test for the incurable illness except in the brain samples of the dead, how to ensure the safety of the world's blood supply?

Dr. Neil Cashman thought he had the answer. The University of Toronto scientist had spent his career trying to sift out the misshapen clumps of proteins thought to cause neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) that hid in a sandbox of normal proteins. In 2002 he finally succeeded, using a chemical agent to alter normal proteins but not so-called aggregated misfolded ones, leaving the clumps easier to detect. It would become the formula for a diagnostic kit usable by blood banks everywhere.

The next challenge was bringing the kit to market. The clock was ticking, particularly in Western European countries, where infected cows continued to crop up. Cashman approached George Adams, a serial entrepreneur who had recently resigned as head of the University of Toronto's Innovations Foundation. Amorfix Life Sciences is expected to introduce the diagnostic kit in Europe in 2007; Adams says the kit will generate $10 million in 2007 sales for the publicly held company.

While detecting VCJD in the blood supply is of pressing importance, what tantalizes investors and clinicians is the prospect of a similar blood test to diagnose Alzheimer's disease. Doctors screen for the illness today using cognitive and memory exams, spinal taps or imaging tests--all pricey, none fail-safe. For the hundreds of companies working on treatments, that means relying on drug trials involving patients who may not even have the disease. "That's why the treatments we have now don't work that well," says Adams. In September, Amorfix announced that its technology can detect aggregated beta-amyloid, the protein fragment that, when gobbed together in the brain, is thought to identify Alzheimer's. With 460 million people worldwide over the age of 65, Adams estimates the market at as much as $5 billion.

Corralling clumps of misshapen protein could open the way not just to diagnosis but also to treatment. In August, Amorfix partnered with Biogen Idec of Cambridge, Mass., to pursue treatment for ALS, or Lou Gehrig's disease, with the goal of blocking the protein from misfolding in the first place. "It's just the most awful disease, and the most challenging," says Cashman, who runs an ALS clinic in Vancouver, where he is research chairman of neurology at the University of British Columbia's department of medicine. "It may sound trite, but I want to make a difference, and this is my calling."