Alzheimer’s cure remains elusive
Despite billions in research over two decades, science is not much closer to an answer
Judging by his online corporate biography, it almost seems the late 2000s didn’t exist for Montreal’s Francesco Bellini.
There is no mention of the once-hot pharmaceutical company he ran — Neurochem Inc. — or the promising Alzheimer’s drug that for a few heady years had investors’ hearts racing.
If the potential of Alzhemed were fulfilled, the Quebec firm’s chief executive told the National Post in 2006, it would be a multibillion-dollar blockbuster and he could “retire anywhere in the world.”
Then, barely a year later, results from Phase III clinical trials came back, and the dream of medical breakthrough and untold riches abruptly evaporated: Alzhemed had little effect on people. His deflating — and costly — experience was hardly unique.
As documented by two new, Canadian co- authored journal papers, Alzhemed was only one among scores of potential dementia drugs over the past two decades that entered the pipeline with high hopes, only to later crash and burn.
Government and independent groups in Britain and Europe have issued calls to action in recent months, noting that Alzheimer’s remains the sole major cause of death in industrialized countries that lacks a disease-modifying treatment — despite billions invested in trying to find one.
“For the clinical trialists in the world … the past 10 years have been frustrating,” says Dr. Serge Gauthier of the University of Montreal, co-author of the two recent articles that outlined the bumpy history of dementia drug development.
Yet the need for medicines to slow down Alzheimer’s is, if anything, more pressing than ever.
The rapid growth in the ranks of Alzheimer’s and other dementia patients — and the high cost of caring for them — not only represents millions of lives devastated by the crippling conditions, but actually poses a “serious threat” to nations’ economic and social development, argues Dr. Gauthier’s paper in Lancet Neurology.
The scientists, part of a “commission” set up by the prestigious Lancet group of journals to tackle the issue, urged governments and industry to boost investment in treatment research significantly.
“It’s an urgent public-health problem we have to address very quickly,” says Dr. Howard Feldman, a world-leading Alzheimer’s researcher at the University of British Columbia.
Experts say it’s important to remove obstacles and allow scientists to learn from each other’s work. Yet this country, for one, still has no national plan to co-ordinate dementia research among academia, government and industry, says Dr. Larry Chambers, scientific adviser for the Alzheimer Society of Canada.
There is good news, though, given effective new diagnostic tools and some promising new drug candidates on the horizon.
But questions remain about why so many past attempts have failed, what it will take to do better in future, and whether some patients will ever be helped by medication.
To Phyllis Fehr, those are much more than academic issues.
The intensive-care nurse, 56, was diagnosed three years ago with early-onset Alzheimer’s.
One of the existing drugs that treats memory loss and other dementia symptoms — but not the underlying disease — has helped lift the fog, she says. Fehr knows it will not work forever, and suspects that any medicine that can actually put the brakes on the illness itself will arrive too late for her.
Four drugs on the market now provide some relief of symptoms for relatively short periods, but can’t curb the disease’s relentless, brain-ravaging progress.
One of Gauthier’s recent papers, an offshoot of a project for Britain’s Office of Health Economics, found there had been 2,000 trials involving almost 900 would-be dementia drugs registered in the last 20 years. Of the studies completed, suspended or withdrawn to date, none succeeded. Just fewer than 200 products are still listed as in development.
Industry involvement is crucial to bringing any drug to market, yet some companies burned by past failures have given up on dementia entirely in recent years, notes Feldman.
Only 3.8 per cent of all pharmaceutical products in the discovery stage and 1.2 per cent in advanced, Phase III trials are for dementia — compared to 31 per cent and 24 per cent for cancer, the British-commissioned study found.
So why is it so hard to make a dementia drug that works?
A key factor has been an exaggerated faith in a particular strategy: attacking just one of the biological origins of Alzheimer’s, says Feldman. Science has well established that proteins known as beta-amyloid and tau spread abnormally in Alzheimer’s-afflicted brains, interfering with neuron transmission and killing off cells.
That led to an assumption that reducing amyloid “plaque,” for instance, would necessarily make demented patients better, says the UBC scientist.
In reality, the solution was not so simple, and time after time drugs shown to reduce amyloid plaque in animals have failed to cause any improvement in humans already experiencing symptoms. It seems a drug that only targets amyloid will have limited effectiveness; the future of Alzheimer’s may be medicines that attack both the plaque and tau, says Gauthier
There are auspicious developments, though. Rapid advances in diagnostic imaging have made it possible to identify people with Alzheimer’s-like changes in their brain before symptoms develop.
And a major, U.S.-based project has taken the rare step of making available brain images and other research to all comers, the kind of scientific sharing that experts say is crucial to moving faster toward a treatment.
Among the experimental drugs that give Gauthier hope are LMTX by Tau-Rx, which is billed as the first tau-targeting Alzheimer’s product but also affects other proteins linked to dementia. A Phase III trial is underway. The University of Montreal scientist also pointed to Eli Lilly & Co.’s highly anticipated Solanezumab, an antibody that binds to amyloid and clears it from the brain. After two failed trials, the company is running another Phase III study.
It’s an urgent public-health problem we have to address very quickly. DR. HOWARD FELDMAN WORLD-LEADING ALZHEIMER’S RESEARCHER AT THE UNIVERSITY OF BRITISH COLUMBIA