‘Neuroprotection’: an elusive goal in fighting brain diseases

About 15 years ago, I wrote an article about treating Alzheimer’s disease that divided treatments into two categories: “symptomatic” and “neuroprotectant.”

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.

Joseph Quinn, M.D.
Professor of Neurology
Layton Aging & Alzheimer’s Disease Center
OHSU Brain Institute

One response to “‘Neuroprotection’: an elusive goal in fighting brain diseases

  1. Hello,my name is Tonya. im currentlly
    here at ohsu,. i trasferred myself over here
    after being in mcminnville, or hospitol for for two days, which was a traumatic ordeal in itself. i almost did not make it out of there. Since ive been here at ohsu ive been ttreated
    with 100 percent respect even when ive been a hard patient to deal with im sure due to all the infection and organ shutt downs, and list keeps getting bigger.but its like they all work together to figure out whats best for me before they take the next step.ive been pretty scared and worried if ide even get out of the hospital anytime soom or regain any of my clients
    left when im able too. then i will have nothing left,because im selfemployeed. and have no way of paying bill now. and have had this buis 15 years.,signed tj

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