Who Dropped the Ball on L-dopa? A Patient's Lament

How’s the war on Parkinson’s disease going? That depends on whether you’re a researcher, clinician, or patient. Researchers can claim that they are making spectacular progress in understanding the disease. Clinicians can argue that they manage the symptoms better than at any time in history. If you’re a patient like me, however, then the honest truth is that the war isn’t going very well. The Holy Grail of biomedical research is an intervention that slows, stops, or reverses a disease—a so-called disease-modifying procedure. Over the last decade or so, Phase 3 clinical trials of diseasemodifying therapies for Parkinson’s disease have reported almost universally disappointing results. When tested under placebo-controlled conditions, the three main disease-modifying approaches—protecting neurons (with drugs like selegiline and rasagiline), reviving neurons (with neurotrophic factors like GDNF and neurturin), and replacing neurons (with neural grafts)—have so far failed to deliver. There are many possible reasons for the failures. It may be that the trial designs were flawed. Or it might be that the interventions didn’t work because the disease pathology in the patients being studied was already too advanced to modify. A landmark paper by Jeff Kordower et al., for example, reported that within 5 years of being diagnosed, Parkinson’s disease patients have virtually no functioning dopamine nerve endings left. If the dream of a transformative disease-modifying therapy still lies a decade or more in the future, what