Earlier this year, Parkinson’s disease (PD) research entered a new era when the Michael J. Fox Foundation announced a major scientific breakthrough: the discovery of a biomarker for Parkinson’s disease. This means that, for the first time ever, we can now spot the earliest known signs of the disease in Parkinson’s patients.
This long-awaited new procedure is called the “alpha-synuclein seeding amplification assay” (SAA) and can detect misfolded alpha-synuclein in spinal fluid, the rebellious protein clearly linked to Parkinson’s disease. It separates, with an astonishing 90% specificity, those who have evidence of PD pathology in their cells from those who do not. It also does this before symptoms appear, much like 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 difficult to overestimate the implications of this development for people living with alpha-synuclein dysfunction. For one thing, we never had any way of knowing who these people were, that is, until the moment of diagnosis, by which time the damage to the brain cells is already well underway. As for the diagnosis itself, which comes as a bolt from the blue for most people, it has always been frustratingly subjective and based essentially on a doctor’s opinion following a brief, not very helpful visit to the doctor’s office. for the provision of medical care, not to mention the development of biomedical drugs.
The new SAA test has already been integrated into drug trials as the first measure that can objectively identify people with the biology we are targeting, giving drugmakers greater assurance that they are testing experimental treatments in the right populations. For biopharmaceutical companies weighing the decision to enter or remain in the high-risk neurological disease space, this changes the investment value proposition. In 2024, we will see an increase in potential new drugs entering the pipeline and progressing along their path to pharmacy shelves.
What is equally remarkable is how the SAA’s breakthrough came about. The search for the biomarker required research and study of “needles in a haystack”: people without traditional symptoms of Parkinson’s disease and who are unknowingly living with a higher risk of contracting the disease. It was crucial to understand what biology distinguished them from those who do not suffer from 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 diseases. (We’re not talking about the short-term loss of smell associated with Covid-19, but a significant, long-lasting loss of smell that persists over years.) For some time now, researchers have known the link between loss of smell and neurodegeneration, particularly 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 people over the age of 60 live with some degree of smell loss, but most don’t realize it until they get tested. If we add to this the fact that all major brain diseases – Alzheimer’s, Parkinson’s, ALS, Huntington’s – are associated with some loss of smell, the result is surprising.
The Michael J. Fox Foundation’s large-scale observational Parkinson’s study aimed to use bad smell as one of the criteria for finding and enrolling at-risk individuals. (We should note that, for this risk group, it is not yet clear If OR When the disease may eventually manifest itself.) The highly sophisticated screening device used? A humble scratch-and-sniff test, albeit the scientifically validated variety.
Until the validation of the SAA biomarker, a reduced sense of smell could not be objectively linked to the presence of the underlying biology of Parkinson’s disease. But we can now report that the test accurately diagnosed the disease in 99% of people with poor sense of smell and so-called sporadic Parkinson’s (in other words, those without the genetic mutation).
In 2024, we will begin to see a sea change in the possibilities for screening and predicting Parkinson’s disease and, quite possibly, other diseases of aging. An annual scratch-and-sniff test could soon become as commonplace as a mammogram or colonoscopy. In 2024, with widespread adoption, this simple, affordable and accessible mechanism will fundamentally change the landscape of what is possible in Parkinson’s research and treatment.