Positive Outlook for the Early Detection of Brain Disease

Earlier this year, Parkinson’s disease (PD) research embarked on a groundbreaking journey as the Michael J. Fox Foundation unveiled a monumental scientific advancement—an identification of a biomarker for PD. This discovery represents a remarkable milestone, marking it the first instance where we can detect the earliest indicators of PD in individuals afflicted with the condition.

This widely anticipated breakthrough introduces a novel technique known as the "alpha-synuclein seeding amplification assay" (SAA). This groundbreaking method can identify misfolded alpha-synuclein proteins in spinal fluid, a protein closely associated with Parkinson’s disease. Impressively, it boasts a staggering 90 percent specificity, distinguishing those displaying evidence of PD pathology within their cells from those who do not. Importantly, it accomplishes this feat even before the emergence of symptoms, mirroring how high blood pressure or cholesterol levels serve as precursors to identifying cardiovascular risk long before a heart attack necessitates a visit to the emergency room.

The ramifications of this development for individuals grappling with alpha-synuclein dysfunction cannot be overstated. Until now, we lacked the means to identify these individuals until the moment of diagnosis, at which point irreversible damage to brain cells is often already underway. Moreover, the diagnosis process itself, typically delivered as an unexpected revelation, has remained frustratingly subjective, relying primarily on a physician's subjective evaluation during a brief office visit. This approach falls short in terms of providing effective medical care and is inadequate for advancing biomedical drug development.

The newly introduced SAA test has swiftly found its way into drug trials, serving as the inaugural method to objectively pinpoint individuals possessing the specific biological traits targeted by drug developers. This offers pharmaceutical companies heightened confidence that they are testing experimental treatments on the right patient populations. For biopharmaceutical firms contemplating investments in the high-stakes realm of neurological diseases, this fundamentally alters the value proposition. In the year 2024, we anticipate a surge in potential new drugs entering the development pipeline, making strides toward eventually reaching pharmacy shelves.

Equally noteworthy is the intriguing manner in which the SAA breakthrough was achieved. The quest for this biomarker involved locating and studying individuals who exhibited no traditional PD symptoms but unknowingly harbored an elevated risk for the disease. Identifying these "needles in a haystack" presented a unique challenge. Surprisingly, the sense of smell emerged as an unexpectedly reliable predictor of brain disease. We are not referring to the temporary smell loss linked to Covid-19, but rather enduring and significant olfactory impairment that persists over years. Researchers have long recognized the correlation between smell loss and neurodegeneration, particularly in conjunction with specific risk factors, such as a diagnosis of REM behavior disorder (RBD), a sleep disorder. Studies have shown that a significant proportion of individuals over the age of 60 experience some degree of smell loss, often without awareness until tested. When coupled with the fact that major brain diseases—including Alzheimer's, Parkinson's, ALS, and Huntington's—are all associated with varying degrees of smell loss, this revelation is truly astounding.

The Michael J. Fox Foundation's extensive observational study on Parkinson's incorporated poor sense of smell as one of its criteria for identifying and enrolling individuals at risk, albeit with uncertainty about when or if the disease might eventually manifest in this risk group. The remarkably sophisticated screening device employed for this purpose was a humble scratch-and-sniff test, albeit one validated by scientific rigor.

Until the validation of the SAA biomarker, a diminished sense of smell could not be conclusively linked to the presence of underlying Parkinson's disease biology. However, we can now report that the test accurately diagnosed the disease in 99 percent of individuals exhibiting poor smell and those classified as having sporadic Parkinson's (meaning those without a genetic mutation).

In the year 2024, we are poised to witness a profound transformation in the landscape of PD screening and prediction, and potentially, other age-related diseases. An annual scratch-and-sniff test may soon become as routine as a mammogram or colonoscopy. With widespread adoption anticipated in 2024, this straightforward, cost-effective, and accessible method will revolutionize the possibilities in Parkinson's research and healthcare.