In the last 15 years, researchers have made significant advances in identifying several genetic causes of familial Parkinson’s disease. Genes are the blueprint for proteins, the biological machines that make our cells work. By understanding the function of the proteins that these genes make, and learning what goes wrong when mutations are present, investigators are beginning to unravel the processes that cause Parkinson’s to develop.
Basic research into how brain cells communicate with each other is critical, says Dr. Austen Milnerwood, a translational neuroscientist at the University of British Columbia. Traditionally, treatment for Parkinson’s has focused on alleviating the symptoms of Parkinson’s. If Milnerwood and his colleagues can correct the changes different mutations induce in the brain, they hope eventually to reverse or prevent the onset of the disease. He has recently received a two-year, $90,000, Pedaling for Parkinson’s New Investigator Award from Parkinson Canada’s National Research Program to pursue this research.
“We will look at the fundamental alterations to brain cell communication that are induced by the presence of these (genetic) mutations, and then try to correct them,” Milnerwood says.
Working with cells cultured from genetic mouse models, Milnerwood studies how the proteins that contain mutations within them affect communication between one brain cell and the next. Mutations in LRRK2 (the most common cause of familial Parkinson’s disease), for example, cause brain cells to become hyperactive, transmitting information too rapidly.
Eliminating the activity of the LRRK2 protein appears, so far, to improve communication among brain cells containing the mutation, by reversing the hyperactive transmission of information. Milnerwood and his colleagues have already administered these compounds to mice without any adverse effects. Now they’re testing to see if the compounds are safe and beneficial to mice that have Parkinson’s disease mutations.
Similar compounds are already being tested in human trials to reverse Huntington’s disease. Milnerwood’s long-term goal is to test whether these drugs will improve the dysfunctional behaviour of brain cells involved in Parkinson’s disease.
“I believe Parkinson’s is a whole brain disorder, and in order to stop the progression of this devastating disease, we have to understand what causes it, not just look at the consequences,” Milnerwood says.
He’s encouraged by the progress researchers around the world have made in just five years on understanding the biological processes involved in Parkinson’s disease. Charting those processes will enable the intelligent design of therapies to stop the disease or protect the brain from its onslaught, Milnerwood says.
“We’ve learned so much over the last five years, that what happens in the next five years will be very exciting.”
Read about other researchers funded recently by Parkinson Canada’s National Research Program.
When Nick Kaethler was diagnosed with Parkinson’s disease 18 years ago, he had just retired from his career as a music teacher. “We decided this was not going to change our retirement plans and we would continue to do the things we really wanted to do,” says Nick’s wife June.
They took to the road in their RV and travelled for the next four and a half years. Next, they took a crash course in teaching English as a second language and spent two years teaching English at a university in China.
All this time Nick was managing his Parkinson’s symptoms well with levodopa. Each year he would check in with his doctor and renew his prescription, before heading back on the road or back to China. Returning to Toronto in 2005, Nick’s symptoms became more severe and new symptoms appeared. He underwent speech therapy and added new medications to his levodopa.
By 2015, Nick’s life was severely curtailed by the advanced state of his disease. “It was like a giant was sucking out my life through a straw,” he says. He was taking medication every two hours to maintain very limited activity. “I was basically able to manage one activity – a meeting or choir practice – for about 40 minutes a day.” He also had arthritis and a fall had resulted in a “half hip” replacement.
“I was really going downhill and losing the will to live,” Nick says. “When I woke up in the morning, I just didn’t want to get up and live.”
The couple began to look for other treatment options. Unfortunately, Nick was not a candidate for DBS (deep brain stimulation) surgery. Fortunately, a new method of administering levodopa had just been approved for treating advanced Parkinson’s. Dr. David Grimes, Director of the Parkinson’s disease and movement disorder clinic at the Ottawa Hospital, thought Nick might be a candidate for the new treatment Duodopa – and the first Ottawa patient to receive it, under the care of Dr. Tiago Mestre.
Duodopa is a levodopa and carbidopa combination in the form of a gel that is delivered directly into the small intestine, through a small opening (or stoma) in the abdomen, delivering a more constant supply of medication throughout the day. The gel is packaged in daily “cassettes” of 2000 mg of levodopa and 500 mg of carbidopa, which is connected to a small pump, weighing about two lbs. The pump is located outside of the body and can be carried in a fanny pack, pocket, handbag or shoulder holster.
Duodopa requires an outpatient surgical procedure to create an opening in the abdomen so a tube can be inserted and positioned in the small intestine. This is done by a gastroenterologist. Daily cleaning and care of the external tubing must be done by the patient or a caregiver, who can be a family member. This helps prevent any infection of the opening. The medication dose is adjusted by a physician.
With a background in nursing, June was easily able to clean the tubing, apply dressings and wrap the tube close to the body with a bandage at night to keep it in place. “This care doesn’t require nursing knowledge,” says June; “anyone can do it with training, but I think it would be difficult to do on your own.” Duodopa’s manufacturer also provides a patient support program.
Nick had his day surgery and began Duodopa treatment in March 2015 and hasn’t looked back. “It’s like magic,” he says. “It’s still tough in the mornings, but within 30 minutes of beginning the Duodopa I want to get up and within an hour I’m planning my day. And that means activities in the morning, the afternoon and the evening. Nick is an avid bridge player and has won a regional trophy. He exercises, plays table tennis and sings in a choir.
Nick wears his pump in a fanny pack when he’s out and at home it rests in a vest pocket. He tried a shoulder holster, but it made him more lopsided, since he already has some weakness on one side. He still takes some oral levodopa at night and still deals with some symptoms, usually later in the day. “He goes through the entire cassette each day,” says June, “and has done so since the beginning.” Not all patients require the full 2000 mg of levodopa, so they will not use all the medication in a cassette.
Nick is fortunate that he lives in Ontario and is over 65 years of age. Duodopa is substantially more expensive than oral levodopa and is not covered by most provincial health plans. In 2014, Duodopa was added to the Ontario drug formulary through the exceptional access program (EAP), which has strict criteria and requires a physician’s recommendation. In Quebec, coverage is granted on a case-by-case basis; in Alberta it is covered under short-term access and a small group has coverage in the Yukon. About 80 per cent of private insurers cover Duodopa, but there is often a co-payment required.
Parkinson Canada was instrumental in getting access to the drug coverage for Ontarians. In 2013, we prepared a patient evidence submission for the Ontario Public Drug Program to support access to this new treatment option. We asked the Ontario Parkinson’s community, people with advanced Parkinson’s and their caregivers to provide us with feedback by completing surveys. We also interviewed Dr. Anthony Lang, in Toronto, who had been involved in the clinical trials of the treatment. We will continue to advocate for access to treatment options in other parts of the country.
In addition to financial coverage, not every health centre in the country is equipped to offer the Duodopa treatment option. At the time of publication, there are centres in Edmonton, Calgary, Toronto, Vancouver, Montreal, Kingston and Ottawa offering the treatment. If you are interested in Duodopa, ask your physician or neurologist if the treatment is offered in your area and what coverage is available.
“I hope this treatment becomes more available for more people,” says Nick. “In my case, it’s been a great success.”
For more detailed information about Duodopa, watch our public education webinar on Neupro and Duodopa online. It includes a thorough presentation on this new treatment option. Visit www.parkinson.ca to learn more about living well with Parkinson’s.
David Blakey on the water Photo credit: Lee Narraway
By David H. Blakey, D. Phil.
There I was, 63 years old, sitting in my 1997 Hudson single behind the start line for the 2015 Head of the Madawaska regatta in eastern Ontario. Cold rain was teeming down as we waited to be called to the start. I had promised myself months earlier that I would race again some day. It had been ten years since I last raced. But this was no ordinary challenge. It wasn’t enough to attain the necessary fitness to race, nor the control of balance and timing in the hull that was only 11 inches wide at its widest point. This was all out war against a disease that was robbing me of my physical being, Parkinson’s disease. This was my Everest.
In the summer of 2011, I went to see the doctor because I was having trouble handwriting. I had also stopped swinging my right arm when I walked, which I had initially attributed to a stressful job. The doctor didn’t like the way I looked and sent me for an assessment at the Ottawa Hospital Neurology Clinic. After some seemingly unusual tests, I was told that I did indeed have Parkinson’s disease.
At first, the disease did not seem to have a very profound effect, but eventually my gait and fine muscle control became impaired. Everything I read emphasized the importance of exercise in coping with Parkinson’s disease. I began to exercise seriously, both in the gym under the guidance of my physiotherapist, and by doing the two physical activities I loved the most; cycling and rowing.
Although the medication I was taking initially worked very well, I eventually developed problems doing aggressive exercise. When I cycled, I had balance problems and my legs couldn’t keep up with the pedals. When I rowed, my balance was poor and I could not keep up with the desired stroke rate. This happened when I was rowing my single alone and also when I rowed in a four-man boat, called a quad, with three of my rowing friends who were willing to tolerate my new reality. These deficiencies were hard to take. I had always been a keen cyclist, biking to work since I was a grad student until I moved so far from work that riding to work became impractical. I had rowed for about as long. To be clear, I am not a natural athlete and I was no super star at either activity, but I loved both sports. Given my size and shape, finishing a race in the middle of the pack was a good result.
Since the onset of the disease, my rowing had been getting steadily worse. Early on, I fell out of the boat twice after not doing so for almost thirty years. I became so unsteady in the boat that I couldn’t row safely on the Ottawa River, where the Ottawa Rowing Club is situated. I eventually began rowing occasionally on the Madawaska River, an hour west of Ottawa, where the water is calmer, shallower, and cleaner. Even there, I was still off balance and rowing poorly. My cycling continued to be slow and unsteady.
In the fall of 2014, my neurologist gave me a different medication to try when I was going to exercise. It worked really well and I was rowing and cycling as though I had never been diagnosed with a chronic disease. I was soon able to return to rowing on the challenging waters of the Ottawa River and I was cycling with greater control and speed. Rowing has been compared to a combination of weight lifting and golf, requiring the strength of weight lifting and the finesse of golf. You use most of your body and technique and timing are so important. The oars have to be manipulated through a complex series of movements with precision or you will swim. Regaining the ability to row, let alone to compete, took a serious effort and I have many people to thank who helped. None of this could have happened without my physiotherapist at NeuroLogic Physiotherapy in Nepean, who prepared me mentally as well as physically, teaching me to appreciate what I had rather than dwelling on what I had lost. My sincere thanks go to the management at the Ottawa Rowing Club who allowed me to keep my boat in their boathouse, while I was not really rowing enough to qualify for a rack, and the incredibly kind people at the Burnstown Rowing Club who welcomed me to row off of their docks and offered to accompany me when I rowed in case I had an accident.
Having vastly improved my performance on the river and the bike paths, I decided to commit to rowing a head race in the fall of 2015. In a head race, rowers are timed as they row over a set distance, much like a 10k running race. To prepare, I rowed as much as I could and when I didn’t row, I often biked so that I was reasonably fit. The day of the race at the Burnstown Rowing Club on the Madawaska River was coming. I had agreed to referee at the regatta (I am a licensed referee), so, I would be at the race site anyway. It was with great trepidation that I took my boat to the Madawaska course. Despite the progress I had made in pushing back against Parkinson’s disease, I was still not able to row as I did when I was younger. Early on, I seemed to have lost my muscle memory, but lately, it seemed to be back. But was that enough? I was terrified of making a fool of myself.
I finished the race. It wasn’t pretty, but I did it. I had trouble breathing and had to stop during the three kilometre race to catch my breath. Nevertheless, this was a massive victory for me. I didn’t win the race, but I didn’t come last either, and I gained so much in the process. This was an accomplishment that will give me the strength and willpower that I will need to face future challenges as I continue to live with Parkinson’s.
I learned some important lessons along the way. You can live a good life with Parkinson’s disease, but you have to push back against the debilitating effects of the disease. You have to exercise, exercise, exercise. Find something you love and do it. It doesn’t matter if you win the race or cycle, swim, or run the fastest, just do it. The victory is in the doing. I am convinced that it allows me to have a better day if I exercise. Finally, set a goal and build a team to help you achieve that goal.