The morning before Thanksgiving 2017, neurologist Reisa Sperling was waiting for news. Sperling, an Alzheimer’s researcher and professor of neurology at Harvard Medical School, had been waiting to hear about the results of an Alzheimer’s trial called Expedition 3, which was gave more than 2,000 people either a placebo or an infusion of the drug solanezumab, meant to slow cognitive decline.

Sperling cared not only because she’s a leading researcher in the field but because her own study, A4, would be testing the same drug—but in a different population. While Expedition 3 required subjects to have amyloid build up in their brains, A4’s trial was on asymptomatic or very mildly symptomatic people 65 and older who have biomarker evidence of brain amyloid deposition.

The Expedition 3 results, which showed some efficacy but not enough, being ruled a negative by the study’s authors were devastating, Sperling told The Daily Beast.

“It was a near miss because every single cognitive measure and clinical measure showed a small benefit but not enough,” Sperling said. “I was so sad for the patients and very worried about A4.”

It can seem disheartening when the words “negative” appear on trial results, especially in the Alzheimer’s field, which has been plagued with very little movement on the clinical end of treatment for years. The disease was first discovered in 1906 by Alois Alzheimer and since then, has been difficult to treat.

Frank Longo, chair of neurology and co-leader of the new Stanford Neuroscience Health Center, told The Daily Beast that the only FDA-approved drugs for Alzheimer’s patients are Aricept and Acetylcholine, each meant to help boost neurochemicals in the brain.

But neither Aricept nor Acetylcholine are actually treating the disease.

“I think those were developed about 20 years ago and unfortunately, it’s the best we have right now,” Longo said.

But still, in the face of decades of negative trial results, Longo hopes medicine can find a treatment for the disease.

“It’s hard, but trials now are being designed in a much more effective way than they were five or 10 years ago that even if it’s unfortunate news, each trial is tending to teach us a lot and the progress is being made faster because of that and it’s giving many in the field confidence that we will have a drug that does work at some point,” he said.

James Hendrix, the Director of Global Science Initiatives for the Alzheimer’s Association, said that he saw many graduate school classmates drop out after facing failure in the lab over and over again. “It takes a certain mentality to be able to say you’ll enjoy the exploration and the journey and be equally curious and able to solve important problems like Alzheimer’s,” he said.

Negative results of one trial can also help direct how other trials are conducted. Sperling, who clearly has the kind of mentality Hendrix mentions, is a prime example. Instead of brooding over the Expedition 3’s negative results, she got to work.

“We discussed with our team and with experts in the field and with the FDA that we had to be bold and try to get an answer at the end of this study, so we made two decisions: We quadrupled the dose [of solanezumab] and extended the trial to be 4 and a half years,” Sperling said.

Sperling’s A4 results won’t be ready until 2022, but she’s hopeful it will yield helpful information. An aspect of so many negative results has been that researchers are trying to attack Alzheimer’s too late in the game, when so much cognitive damage has been done. Sperling likens it to cholesterol: the drugs that have been tried for Alzheimer’s are treating amyloid-beta plaque, which essentially kills brain cells and can build up 20 years before Alzheimer’s symptoms even begin.

“It’s like cholesterol builds up 20 years before a heart attack,” Sperling said.

Hendrix said an important factor is the lack of funding Alzheimer’s receives. According to the Alzheimer’s Association, the National Institutes of Health spends $480 million on Alzheimer’s research compared to $3 billion on HIV/AIDS, $4 billion on heart disease and $6 billion on cancer.

Testing itself for Alzheimer’s is also a financial factor, as a PET scan to see the brain can be costly for patients. Sperling is using A4 as a potential way in to a blood test to screen for Alzheimer’s, by taking blood samples from every patient who screens for A4. This, Sperling hopes, could hopefully lead to a way for anyone at risk for Alzheimer’s to get tested with a blood test before needing a PET scan to diagnose the disease.  

“There are promising blood tests for amyloid, and just like cholesterol I think we’ll have a blood test that’ll at least tell us about risk,” she said.

Meanwhile, Hendrix doesn’t categorize negative results as failures.

“I hate to use the [phrase] ‘failed trials’ because as a scientist, you’re supposed to come up with a hypothesis and then you test it with an experiment and then you figure out if the hypothesis correct or incorrect,” he told The Daily Beast. “And a failure is not whether your hypothesis is incorrect, a failure is if your experiment didn’t give you the data to know if your hypothesis is incorrect.”

Hendrix said that negative results are all part of the scientific process.

“As long as we continue to learn and advance our knowledge, we are getting closer. The problem is that we don’t know where the top of the mountain is, we don’t know if we have 3 more steps or three more miles or three hundred more miles to go, but we know we’re making progress, we’re learning more and more about the disease,” he said.