This weekend, the New York Times offered a sobering report on the history and current status of drug development for cancer. The story offers some important reminders for those following — or working in — Parkinson’s drug development.
In cancer, researchers are trying to develop treatments targeting abnormal cell growth. In Parkinson’s, many scientists believe that modifying the complex metabolic and protein regulation pathways in our brain cells may hold the answer to curing age-related neurodegenerative diseases. In both cases, what we’re trying to target therapeutically are fundamental biological processes in our bodies. Put simply: Biology is hard. Any treatment will have to ideally work within the biological limitations of processes that have been fine-tuned through millions of years of evolution.
As author George Johnson reports, in spite of reductions in some cancers because of preventative strategies (such as public health campaigns to get people to quit smoking),
“There are reasons to believe that cancer… is not so much a disease as a phenomenon, the result of a basic evolutionary compromise. As a body lives and grows, its cells are constantly dividing, copying their DNA — this vast genetic library — and bequeathing it to the daughter cells. They in turn pass it to their own progeny: copies of copies of copies. Along the way, errors inevitably occur. Some are caused by carcinogens but most are random misprints.
Over the eons, cells have developed complex mechanisms that identify and correct many of the glitches. But the process is not perfect, nor can it ever be. Mutations are the engine of evolution. Without them we never would have evolved. The trade-off is that every so often a certain combination will give an individual cell too much power. It begins to evolve independently of the rest of the body. Like a new species thriving in an ecosystem, it grows into a cancerous tumor. For that there can be no easy fix.”
Scientists seeking cures for Parkinson’s and other age-related neurodegenerative diseases may be faced with similar issues. Even if we can eventually identify strategies to distinguish and treat forms of PD that may arise due to environmental exposures or infectious agents, we may still have to deal with the fact that as we age, our cells’ ability to fight off the toxic byproducts of living (making energy and protein throws out a LOT of toxic stuff) just breaks down: whether due to simple aging or because of some sudden alteration/defect. And this happens faster in some folks than others, perhaps due to genetic factors or simple random bad luck.
So what will it take to get to cures? For one thing, an openness to moving past conventional wisdom and dogmatic approaches. One example: the U.S. government’s success in driving malaria out of the American South in the 1930s, which political science professor Daniel Sledge recounted in a recent issue of the American Journal of Public Health. In a story on Sledge’s paper, NPR reported:
“The findings were surprising. It wasn't getting people to sleep under insecticide-treated bed nets, or getting better medications to people who do get infected — two major tactics used to control malaria today in sub-Saharan Africa and Southeast Asia. Instead, the parasite left the U.S., in large part, because the government destroyed mosquito breeding grounds. ‘The primary factor leading to the demise of malaria was large-scale drainage projects, which were backed up by the creation of local public health infrastructure,’ ” [Sledge] says.
As researchers, we have to challenge ourselves to remember that the things we believe “should” work may not, whereas critical keys to success may lie in new or out of the box approaches. We will get to cures, but we need to be realistic about the hurdles we face and take seriously the need for smart, innovative strategies in how we go about this work.
Watch a short video about the realities of drug development and how The Michael J. Fox Foundation is working to problem-solve and speed a cure for Parkinson’s disease.