This recent popular science article looks at the state of research into Alzheimer's disease and other forms of dementia. There is, so far, little tangible progress in the clinic resulting from the past twenty years of efforts in the laboratory. This is the result of a combination of factors, including a doubling of the imposed costs of medical regulation in those countries with the greatest investment in research, a poor high level strategy on the part of many research and development groups, in that they seek to patch over proximate causes and tinker with the late stage disease state rather than address causes, and the fact that dementia is a hard problem to start with. Much of what is funded as dementia research is in fact fundamental science intended to build a better understanding of the biochemistry of the brain and brain aging, a process of establishing a foundation for future work. That in and of itself is an enormous project, and will probably continue well past the point at which the first effective therapies for Alzheimer's disease arrive. That said, the Alzheimer's research community is one of the few in which sizable efforts are being made to address a root cause of aging, the accumulation of forms of metabolic waste such as amyloid-β and tau, by removing it. This is the right direction to take, and it is a pity that it has so far proved to be much harder than hoped.
By 2050, current predictions suggest, incidence of dementia worldwide could reach more than 130 million, at which point the cost to US health care alone from diseases such as Alzheimer's will probably hit US$1 trillion per year in today's dollars. Funding has not kept pace with the scale of the problem; targets for treatments are thin on the ground and poorly understood; and more than 200 clinical trials for Alzheimer's therapies have been terminated because the treatments were ineffective. Of the few treatments available, none addresses the underlying disease process. But this message has begun to reverberate around the world, which gives hope to the clinicians and scientists. Experts say that the coming wave can be calmed with the help of just three things: more money for research, better diagnostics and drugs, and a victory - however small - that would boost morale. "What we really need is a success. After so many failures, one clinical win would galvanize people's interest that this isn't a hopeless disorder."
The NIH's annual budget for Alzheimer's and other dementias jumped in the past year to around $1 billion, and there is support for a target to double that figure in the next few years - even in the fractious US political landscape. Now, he adds, the research community just needs to work out "what are we going to do with it if in fact we get it?". The answer could depend in large part on the fate of a drug called solanezumab. This antibody-based treatment removes the protein amyloid-β, which clumps together to form sticky plaques in the brains of people with Alzheimer's. By the end of this year, researchers are expected to announce the results of a 2,100-person clinical trial testing whether the drug can slow cognitive decline in people with mild Alzheimer's. It showed preliminary signs of cognitive benefit in this patient population in earlier trials, but the benefits could disappear in this final stage of testing, as has happened for practically every other promising compound. No one is expecting a cure. If solanezumab does delay brain degradation, at best it might help people to perform 30-40% better on cognitive tests than those on a placebo. But even such a marginal gain would be a triumph. It would show scientists and the drug industry that a disease-modifying therapy is at least possible.
On a scientific level, success for solanezumab could lend credence to the much-debated amyloid hypothesis, which posits that the build-up of amyloid-β in the brain is one of the triggers of Alzheimer's disease. The previous failure of amyloid-clearing agents led many to conclude that plaques were a consequence of a process in the disease, rather than the cause of it. But those in favour of the amyloid hypothesis say that the failed drugs were given too late, or to people with no amyloid build-up - possibly those with a different form of dementia. For its latest solanezumab trial, researchers sought out participants with mild cognitive impairment, and used brain scans and spinal-fluid analyses to confirm the presence of amyloid-β in their brains. Another group took the same approach to screening participants in a trial of its amyloid-targeting drug aducanumab. Earlier this year, a 165-person study reported early signs that successfully clearing amyloid-β with that therapy correlated with slower cognitive decline.
Link: http://www.nature.co...ementia-1.20949
View the full article at FightAging
