Study Suggests Revolutionary Drug Could Benefit Patients with Early Stage Alzheimer’s

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A trial of a new Alzheimer’s drug has shown it could benefit patients in the earliest stages of the disease, raising hopes that a treatment for the devastating condition may finally be on the horizon.

While the trial was designed to assess the safety of the treatment and not whether patients fared better on the drug, an “exploratory analysis” of the data revealed that the treatment appeared to slow the mental decline of patients who responded to the therapy, according to The Guardian.

New drug raises hope that a treatment for Alzheimer’s disease may finally be on the horizon Click To Tweet

The small study of only 165 people with mild symptoms of the disorder found that a dozen monthly injections of the antibody aducanumab removed clumps of protein that build up in the Alzheimer’s brain.

A leading theory of the disease holds that the steady accumulation of a protein called amyloid-beta in the aging brain kills off healthy neurons and brings about the memory and cognitive impairments experienced by Alzheimer’s patients.

In the trial, the strongest glimpse of mental improvement was seen in patients who had the highest dose of the drug and who showed the greatest reduction in amyloid plaque proteins in follow-up brain scans. These patients did not worsen after six months of treatment.

But the small number of patients enrolled in the study means that two much larger trials, which are now recruiting 2,700 patients in 20 countries, are needed to confirm whether the tantalizing signs of benefit are real.

Alzheimer’s experts welcomed the results, but cautioned that it is too early to know whether the drug will be a help for patients. Other antibody treatments have looked impressive in early studies only to fail later on in larger trials.

John Hardy, a neuroscientist at UCL (University College London) who first proposed that amyloid was a driver of Alzheimer’s disease, said:

“It’s very interesting and nice to see all these positive data, and it has caused genuine excitement in the field, but it’s a very small number of patients and too small to draw any definitive conclusions from.”

The results from the trial led by the U.S. biotech firm, Biogen Inc. (Cambridge MA), and a Swiss company called Neurimmune Holding AG (Schlieren), are reported in the journal Nature. The data were first released at a scientific conference in March last year.

Aducanumab was hailed as a potential treatment for Alzheimer’s when scientists found the antibody in people who aged without suffering the sort of mental decline that goes with old age. It appeared that the antibody prevented the build-up of amyloid plaques and staved off dementia.

When injected into Alzheimer’s patients, one or two in every thousand of the antibodies cross the blood-brain barrier and then latch on to wayward amyloid-beta proteins. Researchers at Biogen believe that other cells called microglia then arrive and clear the aberrant proteins from the brain. The drug appears to be most effective if the accumulation of amyloid protein is blocked before it causes too much damage. The process may start 15 years before people show symptoms.

In the latest trial, some patients experienced side effects. MRI scans showed a shift in the brain fluid that was more common at high doses and in people who carry the APOE type-4 gene, which is a major risk factor for Alzheimer’s disease. The scientists are now working on ways to avoid the side effect or diminish the problems by reducing the doses patients receive.

Today, some 15% of 65-year-olds have a build-up of amyloid but are still symptom-free, according to The Daily Mail. Alfred Sandrock, of Biogen, said:

“I could imagine a time when we would treat people before they have symptoms. We do that now, for example we treat people with high cholesterol before they get heart disease because we would like to prevent heart disease.”

Experts cautioned that it is too early to be certain that aducanumab works. However, the early results have caused huge excitement.

Richard Morris, a professor of neuroscience at Edinburgh University, said:

“The importance of this first step cannot be understated. Let’s keep our fingers crossed for success in the next steps.”

Professor David Allsop, of the University of Lancaster, said:

“These findings could be a ‘game-changer’ if the effects on memory decline could be confirmed.”

Dr. James Pickett, head of research at the Alzheimer’s Society, said:

“These results are the most detailed and promising that we’ve seen for a drug that aims to modify the underlying causes of Alzheimer’s disease.”

Dr. David Reynolds, chief scientific officer of Alzheimer’s Research UK, said:

“These results provide tantalizing evidence that a new class of drug to treat the disease may be on the horizon. It has been over a decade since the last drug was licensed for use in people with Alzheimer’s and there are currently no treatments able to stop the disease in its tracks.”

Steve’s Take: We’ve been down this road many times before, have we not? The tempting glimmer of a possible breakthrough treatment for Alzheimer’s–after over 35 years of trying.

Most, if not all, of us know family members and friends struck with the cruel, eventually fatal disorder. Add to this list beloved actor Gene Wilder earlier this week. And Ronald Reagan, Rita Hayworth, Sugar Ray Robinson, Rosa Parks, Robin Williams, and the list goes on.

Jeffrey Cummings, MD, ScD, is director of the Cleveland Clinic’s Lou Ruvo Center for Brain Health. Dr. Cummings gave an interview two years ago with FierceBiotech, and having scanned the records of clinicaltrials.gov, he’s acutely aware of just how small his chosen field is. And how incredibly unsuccessful.

“The R&D arena has racked up a whopping 99.6% clinical trial failure rate,” according to Cummings’ review of the trial data. “That’s an astounding failure rate,” says Cummings. “It means that none of the disease modifying agents [for Alzheimer’s] have come to fruition.”

“Our field desperately needs new therapies,” Dr. David Knopman, an Alzheimer’s expert at the Mayo Clinic, said at the Alzheimer’s Association International Conference in Toronto, where biotech company TauRx Therapeutics Ltd. (Singapore) reported the failure of its drug candidate. “In defense, our field is still young,” Knopman added–a justification that dismayed some of his colleagues.

“People got into a certain mindset, had a certain set of expectations, and then proceeded on those expectations for 35 years,” said Dr. Daniel Alkon, a 30-year veteran of the National Institutes of Health and now scientific director of the Blanchette Rockefeller Neurosciences Institute in West Virginia. “It was the expectation that amyloid plaques and tau tangles kill brain synapses and neurons,” and that eliminating them will stop the disease, he said. “There were a lot of clues that weren’t true, but because of their mindset, people didn’t see those clues.”

Dr. Cummings drives home the point that the numbers clearly show that there isn’t enough being done about funding new work on Alzheimer’s. The NIH will spend about $936 million this year on Alzheimer’s disease, a 60% boost over 2005, but still just 17% of the money that goes to cancer drug research. Industry leaders, meanwhile, have been cautious about investing in Alzheimer’s drug research as well, particularly in light of recent setbacks.

The number of experimental Alzheimer’s drugs in the clinic has dropped over the past 5 years, Cummings adds, even as the number of patients with the memory-wasting disease grows by millions. And Cummings is hoping to use these numbers to help prod additional investment in the field.

Steve's Take: This latest step against Alzheimer's sounds, feels different. I’m optimistic. Click To Tweet

It isn’t often that researchers in the Alzheimer’s space say anything optimistic about the latest medicine’s odds of beating Dr. Cummings’ 99% failure standard. Why would they? But their carefully worded utterances cited in this story–especially due to their publication in connection with the preeminent journal Nature–tells me the scientific community sees something in these latest data; something new; a glimmer of hope.

Indeed, there still lies a long, winding road ahead to an actual cure for this pernicious disease. But perhaps we’re finally out of the starting gates. I’m not clairvoyant; my prognostications about our local sports teams’ odds for a world championship over the years proves that. But this latest, albeit small, step sounds, feels different. I’m optimistic.

Addendum: Biogen Inc. on Thursday said its investigational therapy for the early stage of Alzheimer’s disease was granted “fast-track” designation by the U.S. Food and Drug Administration, a designation intended to bring promising drugs for serious conditions to market faster.

The drug–called aducanumab–is designed to help clear the brain of beta amyloid plaques, which many scientists say play a role in causing Alzheimer’s, a progressive, memory-destroying condition associated with older age. The treatment is in late-stage clinical trials to assess the safety and effectiveness of the treatment in slowing cognitive decline in patients with early and mild forms of Alzheimer’s.

Biogen plans to provide more details regarding its clinical studies of aducanumab at upcoming medical meetings. (Source: Wall Street Journal)