There were real options in the former category. But the “neuroprotectant” idea was more theoretical — more of a “coming attractions” approach — citing the studies that were underway to identify treatments that would actually save brain cells, protecting those neurons from further harm, and actually slowing or arresting the disease process.
Sadly, despite 15 years of research since, neuroprotection has not come to pass for Alzheimer’s disease, nor for the next most common neurodegenerative diseases — Parkinson’s disease and Lou Gehrig’s disease, also known as ALS. In fact, despite the fact that arresting disease progression is the most important goal for any neurodegenerative disease, we do not have a single proven neuroprotectant strategy.
A story in Neurology Today last month describes the latest failed attempts in ALS: a clinical trial testing a drug named “ceftriaxone” in 500 patients and a second trial testing “dexpramipexole” in 1,000 patients. The second one was the largest clinical trial so far in ALS. Both studies found that the drugs failed to make any difference in patient outcomes, despite very strong “preclinical” and early clinical evidence justifying these multi-million-dollar studies.
Commentators pointed to two key factors:
1) The disease being studied is a heterogeneous disease, so expecting to find a “one size fits all” treatment strategy may be fundamentally flawed.
2) The trials did not incorporate measurements to show whether the drugs were “hitting the target.” So it is impossible to be sure whether these results mean that the overall strategies should be abandoned, or just this particular drug and dose.
The story struck a chord because these are the same issues that plague Alzheimer’s and Parkinson’s disease research, and the stories leave us with the same uncomfortable feeling that we need to do better than this.
We need to be more precise in defining our study population, and more aggressive about incorporating measures to show that we “hit the target” with our treatments.
Neuroprotection is absolutely the right goal, but we need to work harder and smarter to ensure that our clinical trials are robustly informative, even when they fail to show a treatment benefit.