It was in 1817 that London physician James Parkinson first wrote a description of a movement disorder in a detailed medical essay entitled "An Essay on the Shaking Palsy." Even though research in the Parkinson's disease (PD) field continues to progress, there is still no cure for this disease that affects an estimated seven million to 10 million people worldwide. The question arises: why is it taking so long to find a cure?
1. The brain is complicated.
In fact it has been called the most complex object in the universe. The brain contains about 100 billion neurons (nerve cells) and each neuron is connected to up to 10 000 others. And all together these connections are responsible for your thoughts, actions, life itself. So when something is wrong in this very complex brain, it isn't an easy task to figure out where the problem lies.
2. It's not as simple a problem as we thought.
Initially the symptoms of PD were thought to be due to a loss of dopamine alone. This chemical messenger in the brain helps to communicate commands from our brains to our bodies and without enough dopamine, movement becomes erratic - a tremor appears, muscles become stiff and slow.
But in recent years features not related to dopamine have been identified. Pain, incontinence, sleep disturbance, constipation, depression, anxiety and cognitive impairment are a few of these non-dopaminergic manifestations. Much of the research in the past focused on the dopamine system but increased recognition of non-dopaminergic symptoms has shifted the focus and there are many more factors that need to be studied.
3. There is no biomarker.
A biomarker is any indicator that can be measured objectively in an individual with a specific disease. It changes with disease progression and treatment. An example of a biomarker would be your cholesterol level measured in blood work No such marker exists in Parkinson's. and this hinders research. Being able to determine which potential therapies are promising and worth pursuing because scientists can see their effect on a measurable biomarker in the lab would be invaluable.
For example research into treatments for diabetes can look at blood glucose levels as one of their markers because they know that lower blood sugar levels are good for patients. If a treatment under development helps lower blood glucose, then it is worth pursuing. Having some sort of indicator for PD would allow researchers to focus on those avenues that promise the best results.
4. Every patient has their own version of Parkinson's.
Despite some shared symptoms. every Parkinson's patient seems to have their own unique clinical course as well as response to treatment. Although there are some shared symptoms, each patient is fairly unique in how they experience the disease. The diverse presentations of this disease makes you wonder - is this one disease with one cause or are we dealing with a number of related conditions and causes?
5. You can't cure what you don't know.
The more we continue to learn about PD, the more questions arise. If it's not just about dopamine, what other systems are involved? What is causing dopamine-producing neurons to die? What is the common link between all the different manifestations of this disease? How much is genetic versus environmental? Many unanswered questions remain.
6. Clinical trial recruitment for research studies is difficult.
Clinical trials are necessary to see how effective or safe certain treatments, interventions or diagnostic tests are and also for gaining information about the disease and its clinical course. In other words without clinical trials, there can be no better treatments or a cure. Yet close to 85 per cent of all clinical trials are delayed due to recruitment difficulties and a shocking 30 per cent fail to recruit a single subject. So any delay a study faces due to difficulty in finding participants, leads to a huge waste of resources and most importantly time.
7. Clinical diagnosis, particularly in early PD, is not always accurate.
Currently the only true confirmation of whether someone has Parkinson's is at autopsy when abnormal protein deposits called Lewy bodies are found in the brain. One study showed that when Parkinson's is diagnosed based on a physician's evaluation, less than 60 per cent of patients who were diagnosed with early PD, actually had the disease at autopsy. This can affect Parkinson's research significantly since some of the people they recruit to participate, may in fact not have Parkinson's at all which will affect their findings.
8. Drug development is expensive.
For a new neurologic treatment to get from the lab counter to the pharmacy shelf it can take decades and well over a billion dollars. At each stage of drug development, funding has to be obtained and there is always the chance that the process, no matter what its potential, may be derailed due to lack of investment.
9. Lack of collaboration
Although the research landscape is slowly evolving, lack of collaboration within the research and pharmaceutical communities ultimately slows progress of treatment development. Time is wasted when research findings and developments are not shared. Collaboration on the other hand, maximizes the number of minds working on the problem in order to hasten the pace of investigation and drug development.
10. Out-of-the-box thinking is needed but not always supported.
New treatments start as an idea and sometimes the most innovative ideas carry the greatest amount of risk for investors because there is little reason or data to suggest that these initial concepts will translate into medications or other treatments to the benefit of patients. Funding for these new ideas is often difficult to find.
There are definitely challenges that researchers face in the field of Parkinson's but there is a lot to be hopeful about. Progress is being made as we are beginning to understand the complexity of this disease. There is a large, dedicated global community of researchers and clinicians that are investigating many new and potentially successful targets. Through continued collaboration, and concentration of energy and financial investment into the most promising research areas, there will ultimately be a time when Parkinson's will be a curable disease.
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