Results from the trial of a drug in patients with Alzheimer’s disease have been announced at a conference in Washington D.C., with researchers reporting that the drug may be useful in those with early stages of the disease.
Dr Doug Brown, Head of Research, Alzheimer’s Society’s, said:
“Today’s findings strongly suggest that targeting people in the earliest stages of Alzheimer’s disease with these antibody treatments is the best way to slow or stop Alzheimer’s disease. These drugs are able to reduce the sticky plaques of amyloid that build up in the brain, and now we have seen the first hints that doing this early enough may slow disease progression.
“After a decade of no new therapies for dementia, today’s news is an exciting step forward. We will have to wait for the ongoing trials to finish to know the full risks and benefits of these drugs. If they are positive, these drugs will be the first identified to directly interfere with the disease process and slow the progression of Alzheimer’s.
“It’s good news that some people have been receiving the antibody for over three years and it appears to be having beneficial effects. The current trial has finished recruiting participants, so in just 18 months we may get an exciting first look at the final results.”
Prof. John Hardy, Professor of Neuroscience, UCL, said:
“These reports are good news in the same way that a forecast of sunny weather at the weekend is good news. It raises hopes for good weather, but it does not mean good weather is a certainty.”
Prof. Peter Roberts, Emeritus Professor of Pharmacology, School of Physiology & Pharmacology, University of Bristol, said:
“I would very cautiously go along with this announcement possibly being significant, though unfortunately in the media this morning we have the usual ‘medical breakthrough’ spin.
“Whether or not solanezumab proves to be disease-modifying will take some time to establish. The published data so far show only a small statistically-significant effect in the subset of mild cases of AD (not all the mild cases). The cognitive benefits are not astounding and are actually little or no better than the currently prescribed anticholinesterases.
“The sooner we move away from the ‘amyloid hypothesis’, or rather the opposing ‘amyloid’ or ‘tau’ causal dogmas, the better. Alzheimer’s is very complicated and combination, multi-target therapies are much more likely to show promise in modifying the disease process. A number of tau-related immunotherapies are entering clinical trials and, if beneficial, point a positive way forward.
“Aside from pharmacological strategies, our ‘epidemic’ of dementia really needs much more investment in prevention, rather than treatment, by identifying and modifying the risk factors for developing AD (atherosclerosis, hypertension and other vascular problems) that are common in western Europe, Australasia and the USA.”
Dr Tara Spires-Jones, Chancellor’s Fellow and Reader, Centre for Cognitive and Neural Systems, University of Edinburgh, said:
“The solenuzemab phase 3 extension trial results indicate that in people with mild Alzheimer’s, drug treatment slows the disease process a small amount. A more thorough phase 3 trial targeting only patients with mild Alzheimer’s is underway to try and confirm these results. Current results show the drug only achieves small improvements in early stages; however if it proves to be disease modifying in the current phase 3 trial and provides long term benefits, it will be a huge step forward from the current treatment options.
“These results also lend hope to other current clinical trials testing similar drugs in people with rare inherited forms of Alzheimer’s at a stage before any clinical symptoms. From a scientific perspective, this study is exciting as it further validates the amyloid hypothesis of disease pathogenesis and will guide scientists working on more effective disease modifying therapeutics.”
Prof. Richard Morris, Professor of Neuroscience, University of Edinburgh, said:
“My own judgement is that it is likely to be significant, but it is impossible to comment definitively until the results are actually shown. We don’t yet know how big the effect was, whether the subset of patients was but a fraction or a significant number and so on.
“My grounds for suspecting significance is that the new study constitutes positive evidence for the amyloid hypothesis that has been around for over 20 years, whose co-architect of the idea is the British Scientist – John Hardy (now at UCL).
“Many have been anywhere from sceptical to downright dismissive of the idea given the sheer number of failures of antibody studies, of gamma secretase and BACE inhibitors, and of other compounds targeting aspects of the APP to Abeta pathway. However, a complication in assessing all of these has been that the patients on which the idea has been tested may have been too advanced in their stage of the disease for the treatment, indeed any treatment, to be effective. So early diagnosis such as the DYAN trial and the work on the unusual cohort of families in Colombia (South America) constitute an important shift of focus – one that my group has also pursued in animal studies targeting extremely young animals harbouring human APP mutations. Our own (very) limited animal study published in 2007 showed effectiveness when treatment was given prior to ANY plaque deposition, but NO effectiveness once this had started. We also have a new study in review whose findings, I fear, I cannot yet disclose (but take it that they are positive too!).
“If the industry study has successfully identified very early diagnosis patients and finds that antibody treatment is effective in that subset, my own view is that this would more than vindicate the amyloid cascade idea. More than, as the hypothesis virtually predicts that treatments targeting APP would be ineffective if given too late.
“So I am cautiously optimistic, from the perspective of the audience, they should be too. This is not a mouse study, it’s a people study. And that matters.”
Prof. Hardy: I consult on Alzheimer treatment for Eisai Pharmaceuticals and on Alzheimer diagnostics for Cytox
All others: None declared