Parkinson's disease challenge:
OFF times – when for reasons unknown, our Parkinson's medications stop working and our worst symptoms suddenly decide they're taking over.
OFF times can be like entering an alternate reality. For me, it means suddenly slowing down until I feel as though I'm moving through deep sand at a beach, but with my whole body. Everything slows down, even my speech and my thinking. At my worst, I also tend to twist up with my dystonia, making it almost impossible to walk or do anything.
If this happens as my meds are wearing off, that's one thing. It may mean my medications need to be adjusted. Sometimes, however, it just happens. Maybe I am extra tired or stressed for some reason. Fortunately, I don't go through this often and when I do, it's just annoying. For some people with advanced Parkinson's, the OFF times happen one or more times each day and are severe enough to limit their activities.
Fortunately there's a possible solution in the works for those people with advanced Parkinson's disease who have severe OFF times.
A small Canadian specialty pharmaceutical company, CYNAPSUS, has a drug in the works which is close to being ready for market. It's not a new drug, but a new way of delivering a drug which has already been proven effective. This is APL-130277, a form of Apomorphine delivered through a thin strip, like a Listerine® breath strip, but under the tongue.
This is a rescue treatment for those intermittent “Off” episodes, not an alternative to our L-dopa use for daily symptoms. It is used when someone needs to get that boost of dopamine – in this case it is a dopamine agonist – in order to get moving quickly. The medication arrives in the brain and gets to work very quickly.
So, why is this important? The only form of Apomorphine available now is by injection - Apokyn. If you haven't heard of it, it's because it's not used a whole lot. There are downsides to this treatment. I can't imagine attempting to give myself an injection when I'm in this OFF state. I'd probably end up injecting someone else in my family. I am not fond of injections, especially not when my muscles are extremely tight – ie: when I'm in an OFF state.
More about the drug in a moment, but now a word about CYNAPSUS.
CYNAPSUS is a specialty pharmaceutical company. It's small – small enough that their CEO, Anthony Giovinazzo, agreed to speak with me over the phone. Their work is all in research and development. This is a new model in the world of pharmaceuticals which is becoming more popular. I won't claim to understand all the ins and outs of this, but one thing became clear as I listened to Anthony speak about the company. He is passionate about his work.
Anthony Giovinazzo made a choice in 2009. He could either take a job with a larger company and make a lot of money or he could join Cynapsus (then a failing company), turn it around and put all his and the company's efforts into APL-130277. A small research and development company does not have any revenue. They depend on grants and investments from shareholders in order to fund their work. Cynapsus is a publicly traded company in both the US and Canada.
Sometimes, they also depend on someone who is passionate enough to spend money from their own pocket. This is what Anthony Giovinazzo did to get his project off the ground. He knew the need was there for this type of drug and he was determined to see the project through. So he funded the initial research and patent applications as well as the search for large pharmaceutical companies to be approached. They initially weren't interested. At that point he transferred the project in late 2009 to Cynapsus and accepted a very low salary to be its CEO and drive the project forward.
Then, in 2012, the research team at Cynapsus obtained a significant Michael J Fox Foundation For Parkinson’s Research grant to continue their work. The MJFFPR recognized the value in Anthony's project. If you click on the link and read the partnering paper, you will have a clear and concise overview of the company and the drug.
Now, back to APL-130277. It's not totally without challenges. Historically, Apomorphine has been used for such purposes as treating behavioral issues in animals and as an emetic for poisoning victims. This last quality is an absolutely wonderful quality if one needs to throw up quickly, however, it isn't exactly the most desired result when taking it for Parkinson's. To counteract this, the drug is given with an anti-emetic, at least at first. For many patients, the anti-emetic can be stopped after a short period of time, usually 30 to 90 days.
Apomorphine is a unique member of the dopamine agonist family of drugs. Although it has its challenges as described above, it does not seem to have some of the challenges of other dopamine agonists, such as obsessive compulsive behavior. Patients who have difficulty with this family of drugs may be able to tolerate Apomorphine. It's something to be aware of as the research continues.
Cynapsus will conduct more clinical studies starting this month (July 2014) with a 16 patient pilot study to determine proper dosage. The data from this study will help drive the decisions for dosage for another, larger study for patient efficacy, planned to start in December 2014. (Efficacy – the ability of a drug to produce the desire therapeutic effect.) An even larger safety study is planned for 2015.
If all goes well, there could be a medical solution which does not include needles for people with advanced Parkinson's disease who go through these severe OFF times every day. It's looking very promising. Cynapsus is considered a company worth watching by investors and investment analysts. Michael J Fox Foundation gives them their thumbs up.
For me? These last two articles have been good for me in that I have had to explore and research those areas which I generally try to avoid completely. It would be nice if a good diet, exercise, and a positive attitude – all of which are extremely potent remedies – would be all that is needed for anyone with progressive disorders. There are people who will only receive the help they need through these new breakthroughs with pharmaceutical drugs or DBS surgery. Someday, it might be me.
I will continue to push for exercise, healthy diet, humor, dance, and all sorts of positive ways we can learn to live with our Parkinson's disease. Because it's not always enough, I'm grateful for people like Anthony Giovinazzo and his team who have the passion to work in the difficult, ever changing field of pharmaceutical research and development.