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 PD. This means that, for the first time, we can now identify the earliest known symptoms of the disease in Parkinson’s patients.
This long-awaited new method is called the ‘Alpha-Synuclein Seed Amplification Assay’ (SAA) and is able to detect misfolded alpha-Synuclein in the spinal fluid – a protein clearly linked to Parkinson’s. With a stunning 90% specificity, it separates people who have evidence of PD pathology in their cells from those who don’t. It does this even before symptoms appear, much in the same way that high blood pressure or cholesterol levels are used to detect cardiovascular risk long before a heart attack in the emergency room.
It is difficult to overstate the implications of this development for people living with alpha-synuclein dysfunction. For one thing, we never had a way of knowing these people—that is, until the moment of diagnosis, by which point the ongoing damage to brain cells is well underway. As for self-diagnosis, which has come off as a screw-up for most people, it’s always been frustratingly subjective and basically based on a doctor’s opinion after a brief visit to the doctor’s office—not very useful for providing medical care. Let alone the development of biomedical drugs.
The new SAA test is already being integrated into drug trials as the first measure that can objectively identify individuals with the biology of interest, giving drugmakers more confidence that they are testing experimental treatments in the right populations. For biopharma companies making the decision to enter or stay in the high-risk neurodegenerative disease space, the investment value proposition changes on its face. In 2024, we will see an increase in the number of potential new drugs entering the pipeline and making their way to pharmacy shelves.
What is equally remarkable is how SAA came to be. The search for a biomarker required finding and studying “needles in a haystack”: people who don’t have the traditional symptoms of PD and are unwittingly living with an increased risk of developing the disease. It was very important to understand the biology that differentiates them from those who do not get Parkinson’s. But how do you find someone who doesn’t know you’re looking for them?
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 here, but rather the significant and persistent loss of smell that persists over years.) Researchers have long wondered about the link between olfactory loss and neurodegeneration. In particular, they know. In the presence of certain other risk factors, such as a diagnosis of REM behavioral disorder (RBD), a sleep disorder. Research shows that half of people over the age of 60 live with some degree of reduced sense of smell, but the majority don’t realize it until they’re tested. When you combine this with the fact that all major brain diseases—Alzheimer’s, Parkinson’s, ALS, Huntington’s—are associated with some loss of smell, it’s amazing.
The Michael J. Fox Foundation’s large observational study of Parkinson’s used odor as one of its criteria to find and enroll people at risk. (We should note that the risk for this group is still unclear If or when The disease may eventually show itself.) A very sophisticated screening device is used? A simple scratch and sniff test, though scientifically valid.
Until the SAA biomarker is validated, reduced sense of smell cannot be objectively linked to the biology of Parkinson’s disease. But now we can report that the test accurately detects the disease in 99 percent of people with so-called sporadic Parkinson’s disease (in other words, people who don’t have the genetic mutation).
In 2024, we will see a dramatic change in the possibilities for screening and predicting PD and possibly other diseases of aging. Annual scratch and sniff tests may soon become as common as mammograms or colonoscopies. By 2024, with widespread adoption, this simple, inexpensive and accessible mechanism will dramatically change the landscape of what is possible in Parkinson’s research and care.
