Earlier this year, Parkinson’s disease (PD) research entered a new era when the Michael J. Fox announced an important scientific breakthrough – the discovery of a biomarker for PD. This meant that for the first time in history, we could now determine the earliest known signs of the disease in Parkinson’s patients.
This long-awaited new procedure is called the “loading alpha-synuclein amplification test” (SAA) and is able to detect misfolded alpha-synuclein in cerebrospinal fluid – the wayward protein clearly associated with Parkinson’s disease. It separates, with a staggering 90 percent specificity, those who have evidence of PD pathology in their cells from those who do not. It does so even before symptoms appear, similar to how high blood pressure or cholesterol levels are used to detect cardiovascular risk long before a heart attack lands someone in the emergency room.
It would be hard to overstate the implications of this development for people living with dysfunction in their alpha-synuclein. For one thing, we’ve never had a way of knowing who these people are—that is, until the time of diagnosis, at which point ongoing damage to brain cells is already underway. As for the diagnosis itself, which for most people comes as a bolt from the blue, it has always been frustratingly subjective and essentially based on a doctor’s opinion after a brief examination in the doctor’s office – not very useful for providing medical care. not to mention the development of biomedical drugs.
The new SAA test is now being integrated into drug trials as the first measure that can objectively identify people with the biology we’re targeting—offering drugmakers greater confidence that they’re testing experimental treatments in the right populations. For biopharma companies weighing their decision to enter or stay in the high-risk neurological disease space, this changes the initial value of the investment proposition. In 2024 we will see an increase in potential new drugs entering development and making their way to pharmacy shelves.
Equally remarkable is how the SAA breakthrough came about. The search for the biomarker requires finding and studying “needles in a haystack”: people without any of the traditional symptoms of PD and unknowingly living with an increased risk of the disease. It was extremely important to understand what biology set them apart from those who did not get Parkinson’s. But how do you find someone who doesn’t know they’re looking for you?
As it turns out, your sense of smell is a surprisingly good predictor of brain disease. (We’re not talking about the short-term loss of smell associated with Covid-19, but significant and permanent loss of smell that lasts for years.) Researchers have known for some time about the link between loss of smell and neurodegeneration, especially in the presence of certain other risk factors, such as a diagnosis of REM behavior disorder (RBD), a sleep disorder. Research shows that half of those over the age of 60 live with some degree of loss of smell, but the majority do not realize it until they are tested. When you combine this with the fact that all the major brain diseases – Alzheimer’s, Parkinson’s, ALS, Huntington’s – are associated with some loss of smell, it’s staggering.
The large-scale observational study by the Michael J. Fox on Parkinson’s disease aims to use bad breath as one of its criteria for finding and enrolling at-risk individuals. (We should note that this risk group is still unclear if or when the disease may eventually manifest itself.) The highly sophisticated screening device used? A humble scratch and sniff test, albeit a scientifically validated variety.
Until the SAA biomarker was validated, reduced olfaction could not be objectively linked to the presence of underlying Parkinson’s disease biology. But now we can report that the test accurately diagnosed the disease in 99 percent of people with a bad sense of smell and so-called sporadic Parkinson’s disease (in other words, those without the genetic mutation).
In 2024 we will begin to see a huge shift in screening and prognostic capabilities for PD and, quite possibly, other diseases of aging. The annual scratch and sniff test may soon become as common as your mammogram or colonoscopy. In 2024, with widespread adoption, this simple, inexpensive and accessible mechanism will radically change the landscape of what is possible in Parkinson’s disease research and care.
