Symptoms vs. Disease

Parkinson’s disease does not exist.

There is nothing that we can point to and say, ‘that is Parkinson’s’. We have never found it in a brain, recreated it in a dish, nor given it to any animal. What we have are people living with a diagnosis of Parkinson’s. There is currently nothing that allows us to separate the disease from the people that experience it.

We have assumed that there is an underlying biological phenomenon that connects most, if not all, of those diagnosed, but we have no clear signs that what we are looking for actually exists in the form we have envisioned. And yet, we talk about it as if we know it does. Medical journals are filled with phrases like ‘model of Parkinson’s’ and the ‘pathophysiology of Parkinson’s’ without mention of who any of the underlying biology applies to.

We even have two distinct categories of putative therapies: ‘symptom modifying’ and ‘disease modifying’. But how do we modify what we cannot define in those we want to treat? The most widely used method for tracking this disease is the UPDRS (or, in its longer name, the Unified Parkinson’s Disease Rating Scale), which includes a series of motor tests that output a single number. Generally, the longer it has been since a person’s diagnosis, the higher that number might be. Disease modifying trials aim to slow, stop or reverse that trend. The problem is that the UPDRS is a test of the patients’ motor symptoms, which uncovers nothing about the underlying disease, let alone the biology. So why the distinction?

For decades experts have acknowledged that Parkinson’s has a “multi-causal heterogenous etiology” that results in a wide spectrum of expression. Yet, despite all that we have learned of its complexity, and the array of neurochemicals and brain regions and cell types involved, we continue to examine single-pathway therapies that target large cohorts of individuals, acting as if one pharmacologic approach stands a chance of overcoming the heterogeneity.

So, how should we proceed? Well, until we have reliable biological markers of the diseases affecting individuals and not just of their symptoms, we should dispense with any claims purporting to have found a “biomarker of Parkinson’s,” let alone, “disease-modifying treatment of Parkinson’s”.

After all, for patients, symptoms are the disease. People cannot feel genetic mutations, or mitochondrial dysfunction; we only feel their macro effects. Until we have some means of accurately distinguishing them, the blurry line between symptoms and disease will continue to distort our attempts to treat people.

– Benjamin Stecher

* The featured image was made available courtesy of Marina Noordegraaf (https://verbeeldingskr8.nl/sparkinson/home/en/)

Leave a Reply