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Welcome to e-ParkinsonPost!
This issue looks at research from the perspectives of clinician-researchers, clinical trial participants and ethicists, among others. We also alert you to exciting new research projects funded by Parkinson Society Canada.
You will find a link to our new information sheet on Parkinson’s medications and a summary of novel and promising treatments that are currently in the pipeline.
Our thanks to Teva Neuroscience for sponsoring this issue of e-ParkinsonPost.
Your comments, questions and story ideas are always welcome. You can send them to firstname.lastname@example.org
We wish you all the best of the season.
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.”
First Person – Else Manz
At 58, I was proud of my healthy diet, active lifestyle and my near-empty medicine chest which held only calcium and vitamin D. Life was good. However, I had also spent a full year quietly reviewing many sources, including my nursing texts, to determine the probable cause of the resting tremor in my right hand.
On March 31, 1998 I had my consultation with the local neurologist. It didn’t take him long to confirm my suspicions. He asked permission to call a Saskatoon neurologist who was looking for people who were newly diagnosed with Parkinson’s and not taking medication to participate in a clinical drug trial.
The Saskatoon neurologist sent me an informed consent document to review. It described an investigational drug that had already been tried on a small group of patients. Now my questions took centre stage: If I do not participate in the study, what are my options for treatment? Does the trial drug resemble the makeup or action of one already available? Would the drug delay the progression of Parkinson’s? Does excretion through the liver and kidney mean the possibility of a negative effect on those organs?
I was impressed by the gentleness, thoughtfulness and patience with which my questions and those of my husband were answered. What did I have to lose? I could experience side-effects but there was also the possibility this could be a win-win opportunity.
May 6, 1998 marked my first visit as a participant in the study. I understood that I would be randomly assigned to one of three groups during the initial six months of the study: participants receiving 1 mg of the active drug; participants receiving 2 mg of the active drug; or participants on placebo.
After 28 days, I would return for a check of vital signs, have blood and urine samples taken and undergo neurological testing. Five more visits were scheduled during the first six months of the study. I thought the monitoring process couldn’t be better.
Since my husband and I were both working full time, we decided to treat these 500 km round trips, from Regina to Saskatoon, as family holidays. We would take a different route home from each appointment and have dinner, shopping trips or visits along the way.
Following the initial study, I was asked and agreed to participate in additional studies and sub-studies. The most difficult requirement of one study was having to avoid eating any foods containing tyramine. This meant having to give up some of my favourites such as pizza and lasagna.
In 2003, I learned that I had been taking the active drug. I later received copies of the research published in the scientific journal. Articles concluded that the positives certainly seemed to outweigh the negatives.
When Health Canada approved the drug, I felt fortunate that I had the privilege of access to the medication for the previous eight years. The study came to a close in 2006 but I remain on the medication to this day.
First Person – Penny McDowell
It was the shaking hand that caught my doctor’s attention. I was in his office for my regular checkup but he was saying, “I guess I’d better send you to a neurologist because it looks like you could have Parkinson’s.” I was totally shocked on that last day of February, 2005.
By the time I got a formal diagnosis, in April 2006, I was experiencing a few more symptoms such as muscle stiffness and sciatica-like pain. I had also lost my sense of smell and wasn’t as confident on my feet; my balance was a bit shaky at times. I was feeling a lot of anxiety, too.
My neurologist told me there was a research study looking for candidates in the early stages of Parkinson’s and asked if I would be willing to participate. He thought I might be a good candidate because my symptoms were not that severe.
I read the information the clinic gave me and did my own research online. I learned that the investigational drug had been tested in other countries and had shown some promising results. I decided to be proactive and join the trial. I thought this would be a good opportunity to help myself with one of the latest Parkinson’s therapies while contributing to Parkinson’s research.
One of the greatest benefits of being in the trial was the amount of time the doctors and nurses spent with me during the follow-up visits which lasted up to two hours. It was a tremendous learning experience spending that much time with people who were knowledgeable about Parkinson’s. You feel supported and more confident when you know what’s happening and that you’re being treated. I felt better being in the trial and having that kind of care. The resources were also phenomenal. There were neurologists, nurses, a social worker, occupational therapist and physiotherapist. Everything for movement disorders was under one roof.
The original clinical trial has ended but I am in a follow-up study. My neurologist feels that I’m doing well. I still have a tremor in my left hand and leg but haven’t experienced any major incapacitation after four years on the drug. I’m on no other medications for Parkinson’s and I’m still functioning well day to day, if a bit slower. I try to maintain a healthy lifestyle and pace myself.
For more information on clinical trials, including benefits and risks, questions to ask and a description of the phases of clinical trials, visit the Parkinson Society Canada web page, Clinical Trials and Research Studies.
Clinical trials that are well-designed and well-executed offer excellent opportunities for eligible participants to:
- Play an active role in their own health care.
- Obtain referrals to a study site.
- Engage care partners as companions in care.
- Gain access to new research treatments before they are widely available.
- Obtain expert medical, sometimes multidisciplinary, care at leading health care facilities during the trial.
- Help others by contributing to medical research.
- Enhance personal knowledge of a medical condition.
There are risks to clinical trials.
- Depending on the study design, there may be no guarantee that the participant will receive the active ingredient.
- There may be unpleasant, serious or even life-threatening side effects to experimental treatment.
- The experimental treatment may not be effective for the participant.
- The research may require collection of data, for example, genetic information, that could potentially cause psychological or informational harm.
- The research criteria may require lifestyle modifications, for example, dietary changes.
- The protocol may require more of the participant’s time and attention than would a non-protocol treatment, including trips to the study site, more treatments, hospital stays or complex dosage requirements.
- The experimental drug may not be approved by Health Canada and, if approved, may not be covered under provincial drug formularies.