Things aren’t always as they seem with Parkinson’s disease with one recent study showing as many as half those diagnosed with the disease don’t have it, according Dr. J. William Langston.
At a recent visit to 23andMe, Langston, a pioneering Parkinson’s researcher as well as the founder and chief science officer of the Parkinson’s Institute, gave a quick overview not just of the challenges around diagnosing the disease but also some of the more hopeful recent findings.
Both a friend of 23andMe and a scientific advisor for 23andMe’s Parkinson’s research community, Langston’s presentation offered scientists here a quick overview of the shifting understanding of Parkinson’s.
The traditional view is that Parkinson’s is a movement disorder triggered by a loss of dopamine containing neurons in the substantia nigra, a particular region of the brainstem. But because diagnosis is so difficult, sometimes people with Parkinson’s-like symptoms are misdiagnosed with the disease itself.
In truth, a definitive diagnosis for the disease requires a post-mortem examination to confirm the presence of abnormal protein deposits in the brainstem called “Lewy bodies.” These clumps are loaded with a protein called alpha-synuclein. One promising development in the effort for diagnosis are new techniques for detecting alpha-synuclein, and related structures known as neurites. What’s also been interesting is that scientists have found alpha-synuclein deposits not just in the brainstem, but in other regions of the brain as well as the gut and heart. These same regions may be associated with non-motor symptoms that Parkinson’s patients deal with including such things as a change in their sense of smell, constipation or sleep disturbances.
Like many diseases, the earlier it is diagnosed the better the outcome for patients. Even though there is no cure for Parkinson’s there are treatments and interventions that can manage some of the symptoms and help patients maintain their quality of life. But diagnosis – especially early on – is very poor.
To illustrate that point, Langston, who has been a long time scientific adviser to 23andMe Parkinson’s research community, cited a recent study showing about half of the cases were misdiagnosed. The study was of patients who’d died within five years of being diagnosed with Parkinson’s, but autopsies of the patients revealed that about 50 percent didn’t have the disease. This has enormous implications for research especially clinical trials of disease modifying therapies, which need to recruit patients early in the disease process.
An extensive review of Parkinson’s disease genetics that Langston and his collaborators recently submitted for publication suggests that this confusion is not limited to clinical diagnosis. Looking at 31 different genetic markers associated with inherited Parkinson’s, his team found that only three have been shown to also be associated with the classic pathological features of Parkinson’s. In addition, researchers have found in doing autopsy on patients that even those who share the same genetic marker (one associated with Parkinson’s disease) the kind of protein bodies found in their tissue and where they are found, can be very different.
To try and manage this confusing situation Langston and his colleagues proposed the name Multisystem Lewy Body Disease (brain, spinal cord and peripheral autonomic nervous system) to better reflect what the researchers have found.
Despite all of this, Langston said that there are promising new diagnostic and treatment tools currently in development.