Lansbury and two investors founded a company, Link Medicine, and began screening libraries of chemical compounds for those that would increase autophagy, a natural process that clears away unwanted protein aggregates. Eventually they had a lead autophagy-boosting compound, LNK-754, that worked well in mouse models and appeared safe in human volunteers. In principle, LNK-754 could be useful in treating a number of illnesses including Parkinson’s, Alzheimer’s, and Huntington’s diseases. All that remained, it seemed, was for a large pharmaceutical company to buy the marketing rights and fund the large-scale clinical trials needed to prove LNK-754’s efficacy in humans.
But that hasn’t happened. “It used to be that if you had a drug whose mechanism makes sense, a drug that works in animals and is safe in people, you could immediately go and do a large clinical trial. But for drugs against neurodegenerative diseases, those days are gone,” says Lansbury.
The problem is that for these diseases, the standard measures needed in a conclusive clinical trial—such as cognitive test scores, for Alzheimer’s patients—are expected to show clear evidence of a treatment effect only very gradually, and only in a population of at least hundreds of patients, even for a drug that works. For a would-be disease-modifying drug, that typically means a trial of at least 18 months, costing on the order of $100 million. At the same time, pharmaceutical companies are all too aware that potential neurodegenerative disease treatments have almost always failed in clinical trials, in recent years. “The big pharma companies have become very risk averse,” Lansbury says. “The big issue now is not really the lack of drug strategies, it’s the inability to assess those strategies in short, economical trials.”