Recently the Wall Street Journal reported on drug companies sharing research data in an effort to solve problems with developing treatments for neurological diseases.
Here’s the Economist interpretation of both the problems and efforts at solving them.
It seems to us the main problem comes from an inability to diagnose and measure the different diseases – and we’re working on that.
Alzheimer’s disease: No end to dementia | The Economist
DRUG companies are notoriously secretive. The clock starts running on a patent when it is filed, so the longer something can be kept under wraps before that happens, the better for the bottom line. You know something is up, then, when a group of these firms announce they are banding together to share the results of abandoned drug trials. And on June 11th several big companies did just that. They publicised the profiles of 4,000 patients from 11 trials so that they could learn from each other’s failures. An act of selflessness, perhaps, but also one of desperation.
Alzheimer’s disease is one of those things that policymakers would rather hide from. It is, perhaps, the classic illness of old age. Physical frailty is expected, and can be coped with. Mental frailty is much scarier for the sufferer and more demanding for those who have to look after him. It is expensive, too. Alzheimer’s is estimated to cost America alone some $170 billion a year. And it is getting commoner as average lifespans increase. The number of people suffering from the disease is expected to triple by 2050. Effective treatments would thus be embraced with enthusiasm by sufferers and society alike. The right Alzheimer’s drug could earn a drugmaker a lot of money. The incentives are there. But the science has still failed to deliver.
At the turn of the century, Alzheimer’s research seemed promising. A flurry of drugs which treated symptoms of the disorder had just hit the market and researchers were setting out confidently on a deeper investigation of its causes. Understanding those, they felt sure, would result in a cure. It still might, but the truth is that the hoped-for understanding has not come. As a consequence, a long list of would-be cures have failed in late-stage clinical trials, at enormous cost to the companies producing them. The latest of these, Dimebon, made by Pfizer, was abandoned as recently as March, after $725m had been spent on research and development.
The problem of what causes Alzheimer’s is profound. The physical manifestations of the disease that Alois Alzheimer noticed in 1906 are sticky plaques of one type of protein, now known as beta-amyloid, and nerve-cell-engulfing tangles of a second type, called tau protein. Since 1991 the smart money has been on the hypothesis that the disease is caused by the plaques, and that the tangles are mere consequence. For the past two decades, therefore, most attention has been given to developing drugs that will remove amyloid plaques from an affected brain. Five drugs that do this are on the market, but they only delay the onset of dementia. Once their effectiveness has run its course, memory loss and cognitive decline progress unimpeded, and sometimes even accelerate.
Partly as a consequence of this, the plaque theory is waning. Most researchers still believe beta-amyloid is the culprit, but the idea that free-floating protein molecules, rather than the proteins in the plaques, are to blame is gaining ground. This idea is supported by a study published in April in the Annals of Neurology, which showed that mice without plaques, but with floating beta-amyloid, were just as weakened by the disease as mice with both. If that is true in people, too, many more drugs now in clinical trials may prove to be ineffective.
Another fundamental problem is that, whatever is causing the damage, treatment is starting too late. By the time someone presents behavioural symptoms, such as forgetfulness, his brain is already in a significant state of disrepair. Even a “cure” is unlikely to restore lost function. A biochemical marker that indicates the progress of the disease would thus help identify those for whom early action would be advisable, and might help to distinguish people with Alzheimer’s from those with the less hostile forms of forgetfulness that tend to come with old age. Such a marker would also benefit the organisers of clinical trials. They would be able to see more easily whether a drug was working.
To this end, the Alzheimer’s Disease Neuroimaging Initiative (ADNI), established by America’s National Institutes of Health (NIH) in 2004, is measuring the levels of certain proteins in the cerebrospinal fluid of people who may have Alzheimer’s or may go on to develop it. Though the project still has a long way to go, it has already helped develop a test to diagnose the early stages of the disease.
ADNI’s anagram DIAN, the Dominantly Inherited Alzheimer Network, based at Washington University in St Louis, is taking another approach to the biomarker question. Its researchers are studying families with a genetic mutation that triggers the early onset of Alzheimer’s. That terrible knowledge means it is possible to predict which members of a family are destined to get the disease, and compare their biochemistry with that of relatives who do not have the mutation.
It is hard pounding, however, and—as the drug companies’ confession suggests—it is the “R” rather than the “D” of research and development that needs to be emphasised at the moment. A bad time, then, to be cutting back on “R”. That tripling of future sufferers is going to be expensive. Yet Alzheimer’s research, on which the NIH spent $643m in 2006, is to receive only $480m in 2011. It has not been singled out for these cuts. They are part of a general belt-tightening at the agency. But in this as in everything, you get what you pay for. And that might, in the future, be an awful lot of witless, wandering elderly.