Alzheimer's disease and the search for the silver bullet

Last week brought a disappointing blow to the development of new treatment options for Alzheimer’s disease when Medivation and Pfizer’s Dimebon (latrepirdine) failed the Phase III CONNECTION trial. Results from the CONNECTION study showed that Dimebon didn’t meet its primary and secondary efficacy endpoints and failed to differentiate from placebo, sending Medivation’s stocks crashing by more than 65%. There was a lot of positive anticipation before the results were released; the Phase II trial had shown that a three-times-daily 20mg dose of Dimebon preserved function in patients at or near their original levels on entering the trial across all key aspects of Alzheimer's disease; specifically memory and thinking, behaviour, activities of daily living and overall function. (Medivation press release)

Dr Mark Smith, a consultant to Medivation and professor of pathology at Case Western Reserve University, said he expected the CONNECTION trial results would not be as good as the Russian trial but even replicating 50% of the original results would be meaningful to patients. (Financial Times)

In the UK alone there are nearly 685,000 people living with some form of dementia. This is expected to rise to 940,000 by 2021, and 1.7 million by 2051, according to the Alzheimer’s Society.

With an ageing population, the prevalence of diseases like Alzheimer’s can only rise and while current therapies can alleviate symptoms there are no available options to stop its progression.

The next treatment expected to announce Phase III results is Johnson&Johnson’s bapineuzumab, a humanised monoclonal antibody targeting β-amyloid, followed closely by Lilly’s solanezumab which is currently in Phase III trials. Both of these agents work by clearing existing β-amyloid deposits from the brain or by hindering their formation. The dominant view is that other processes considered hallmarks of Alzheimer’s occur downstream from β-amyloid plaque formation.

There is a lot of scepticism surrounding Alzheimer’s treatments, with few patients continuing treatment long enough to see any real benefits. Quoted in the Financial Times, Dr Gary Kennedy, director of the division of geriatric psychology at Montefiore Medical Center in New York, said “We’re not close enough to the cause of this illness to get the silver bullet. People have to be really cautious about this.”

Despite the lack of definite causality, there are hopes that we will one day have a therapy to treat the underlying disease, not just the symptoms of Alzheimer’s. Meanwhile, symptomatic therapies, such as Aricept, Namenda and Exelon, remain important and are likely to remain the mainstay of treatment.

Turning scientists into entrepreneurs

Blog authored by Julie Walters, Tudor Reilly.

News that the UK’s Royal Society is putting its research fellows through a Business of Science programme at Imperial College Business School is welcome news. The journey from Albert Einstein to Bill Gates can be a long one.

Most biotechnology companies are started by scientists who are passionate about their research. But a company will need a lot more than passion for science if potential drugs are to make the journey from bench to bedside.

Bill Gates once famously said: “If I was down to my last dollar, I’d spend it on public relations.” Unfortunately, public relations or PR is often the last thing scientists think of when they launch a company. First, rightly enough, comes the three big Ms: management, money and markets. But increasingly, PR is next on the list, to help build and guard reputation.

There are still some who think that the science should speak for itself. The only flaw in that plan is that most people, including investors, don’t understand the science. I’ve heard investors complain that they had to watch a pitch presentation several times before they understood the potential application. The company in question was lucky to have found a patient investor! Most won’t be so lucky.

PR builds and maintains credible and sustaining relationships with investors, business partners, potential consumers and regulators. And in the beginning that can mean helping management to define a message and a story that can be understood by the outside world. Not an easy task but one that has to be done – the earlier, the better.

Scientists unlock the secret of ageing

Last week a team of researchers from Newcastle University and the University of Ulm, Germany, claimed to have discovered the biochemical pathway involved in ageing, unlocking the secret of how living cells grow old. This discovery could have significant implications for research into age-related diseases, such as heart disease and diabetes. These findings come hot on the heels of the identification of a gene which determines how quickly people age, reported in Nature Genetics earlier this month (read Peter Coë’s blog on the discovery of this gene, “How we age”, 8 February 2010).

The research, published in Molecular Systems Biology, hypothesised that cells become senescent (a state in which cells stop dividing and their tissue shows signs of deterioration) due to a feedback loop triggered by a DNA damage response. In other words, when a cell detects serious damage to its DNA - which occurs naturally from the wear and tear of life – it sends distress signals to the brain, triggering the cell’s mitochondria to produce free radicals which in turn reduce its ability to support tissue regeneration and repair.

An article published in the Financial Times described how Thomas von Zglinicki, leader of the research team and Professor of Cellular Gerontology at Newcastle University emphasised the need for caution with further research into cellular senescence. “It is absolutely essential to tread carefully in trying to alter processes that cause cells to age, because the last thing we want is to help age-damaged cells from breaking out to become malignant”, he said.
Nevertheless, this discovery has great potential for improving our understanding of diseases linked to cellular senescence, such as atherosclerosis and diabetes.

Patient Voice

Blog authored by Julie Walters, Tudor Reilly.

Last week’s Economist Pharma Conference in London heard how patients are helping to shape future treatments.

Jon Achenbaum of Bayer Healthcare Diabetes Care shared two examples of how patients have been involved in the design of two new treatments.

The first, Contour USB, is a new way to monitor blood glucose levels – a glucometer on a thumb drive. The second is a monitoring device for kids called Didget that plugs into a PlayStation.

Diabetics need to proactively manage their glucose, Jon told delegates, so there is a real motivation for patients to have a say in how they do that.

The new patient-centric ideas resulted from a visit by an innovation team from Bayer which spent five days in a diabetes clinic to understand more fully how patients manage their condition and to hear their ideas.

Living up to the maxim “the best way to get a good idea is to start with a lot of ideas”, the Bayer team came back to HQ with hundreds of new possibilities. They were then whittled down to the best few, which went forward for development.

“If you were a patient, who in this room would not like to be involved in the solution?” asked UCB’s CEO, Roch Doliveux in the same panel discussion as he talked of the sea change taking place in the corridors of power. “In the past,” he said “we’ve talked at patients, not with them” but that had changed. Among other things, patients had helped UCB engineer a new syringe, designed by patients for patients with rheumatoid arthritis.