Bench to bedside: the challenges


We have asked three clinician-researchers to outline some of the challenges of getting new therapies from the lab to the person with Parkinson’s.

The drug development process is lengthy. “The process of going through all the pharmacological studies in basic science and in different types of animals takes a long time,” says Dr. Michel Panisset, a neurologist and associate clinical professor in the Department of Medicine at the University of Montreal. “We have to make sure of the mechanics of the drug and see that it doesn’t kill any living being before we try it out in healthy human volunteers. A large number of compounds fail one of these tests prior to getting to humans.”

Add to that the clinical trials to ensure that the treatments are tolerable and effective, first in healthy volunteers and then in people with Parkinson’s. “There are no really good shortcuts we can use without jeopardizing the safety of the medications,” says Panisset.

Animals don’t get Parkinson’s. “We have to make them Parkinsonian by giving them drugs and killing brain cells manually but that’s not what happens in reality,” says Dr. Mandar Jog, director of the Movement Disorders Program at the London Health Sciences Centre. “The complexity of the animal system is very different from that of the human brain. Often, the chemical or treatment you’re studying in an animal doesn’t transfer easily to the human world, so what works there may not work in humans.”

Additionally, Jog notes:

The brain is very complicated. “The brain has over one trillion connections. It’s not like other organs, such as a kidney, that you can remove and replace.”

Most bench work is done by scientists who know little about clinical medicine; they don’t see patients. “For scientists to translate their lab findings into the human world requires that clinicians get involved, but often, clinicians get involved late and are not able to interpret the scientific data or take it for granted. We need more people who are both basic scientist and clinician, who have the background to understand the lab language and translate it. Or, at least, there should be strong collaboration with clinicians.”

There is also an issue of how do you define bench? “If by bench, you mean simply asking research questions, then you can ask clinically relevant questions, as we just did in our recent research looking at swallowing and gum chewing. We didn’t test it in animals and we didn’t try to figure out what the basic mechanism of sensory neural control for swallowing is in an animal model and then test that hypothesis at the bench level. We simply figured that people say that gum chewing is good for teeth. Why not give gum to people with Parkinson’s and see if it helps them? We did and we’ve shown that swallowing improves. We don’t understand yet how that happens but this is also a form of bench to bedside research.”

Both the public and scientists want early success. “There is a challenge to do the science so diligently that you’re as sure as you can be before jumping the gun and saying, this looks good in a few rats, let’s try to do a big clinical trial.”

Clinical trials are an artificial scenario. “No matter how much you try to randomize patients, there is still a bias in selecting patients. As well, the patients who are willing to participate in trials are motivated people. They may have a different chemistry in their brains from the people who are not motivated to participate; hence the disease impact may be different. Also, many new drugs work well in clinical trials, even in humans, but when the drugs are given to people in the general population, where the variation of the disease in patients is much higher, the results aren’t as impressive.”

A huge challenge of bench to bedside is patients asking, on a regular basis, about unvalidated claims of interventions [treatments] that are completely untested. “Pursuing these avenues takes away important funding from research based on diligent, well-thought-out scientific questions. Passion-driven science is likely the biggest hurdle.”

Dr. Oksana Suchowersky, professor and director of the Movement Disorders Program in the Department of Clinical Neurosciences at the University of Calgary adds her perspective:

Parkinson’s is a very slowly progressive condition and symptoms are quite variable from person to person. “That is why we need to do clinical trials on a large number of patients, and the trials have to run for several years, particularly those for neuroprotection. We also have to follow the scientific method, with placebo control. This is both to make sure that the drug or compound works, as well as determining that it is not harmful.”

“We still do not know the cause of Parkinson’s which makes it very difficult, if not impossible, to find a cure.”

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