Recent failures of two clinical trials into Alzheimer’s disease have lead to fears over the future of research to find new treatments. Dr Eric Karran, Director of Research at Alzheimer’s Research UK, explains what can be learned from these trials, and why now is not the time to give up.
The recent failure of two phase 3 clinical trials for Alzheimer’s drugs is a blow to the field. Like three previous drugs that also failed in trials, these two antibodies – bapineuzumab and solanezumab – worked by targeting a protein called amyloid, which builds up in the brains of people with Alzheimer’s. These findings will also provoke pharmaceutical companies to question whether they can continue to invest in clinical research for such a challenging disease. But now is not the time to give up, and these perceived failures could in fact hold the key to future success.
The latest findings may call into question the role that amyloid plays in the disease, since none of the drugs that have so far targeted the protein have met their goals: improvements in thinking and the ability to carry out everyday tasks. But there is still a solid body of evidence to suggest that amyloid plays a crucial role. Rare genetic mutations that are known to cause some cases of early-onset Alzheimer’s are all involved in the production of amyloid, giving a clear indication that it is a key player in the disease. Researchers now know that amyloid begins to deposit in the brain about 15 years before symptoms appear. There is much evidence suggesting that this build-up of amyloid may be an early ‘trigger’ for Alzheimer’s, kick-starting a chain of events that ultimately leads to the death of brain cells.
Research to date has shown that the role of amyloid is hugely complex, and scientists are still uncovering more information that could aid future drug development. There is also much data yet to be published on these failed trials. Careful analysis and a comparison of the data from both of these trials may well provide insights that could inspire future success.
With bapineuzumab, understanding why the drug failed will be crucial to developing treatments with a better chance of reaching their goals. For solanezumab, early reports suggest that there may have been some benefits for patients with mild Alzheimer’s disease – adding weight to an emerging theory that drugs targeting amyloid would need to be given early to be successful. If we can find a reliable and inexpensive method of identifying people on the cusp of amyloid build-up, but who have not yet developed symptoms, then drugs that target amyloid could have a good chance of bringing real benefit. Meanwhile, work on treatments that attack different features of the disease must also continue.
Other treatments targeting amyloid are already in the earlier stages of development, but with pharmaceutical companies looking for a return on the massive investment needed to develop a drug, there is a danger that these latest results may cause them to reconsider their strategy. Our task is to help solve this difficult problem – that means charities like Alzheimer’s Research UK, Government and the pharmaceutical industry working together.
Current treatments can help relieve some of the symptoms of the disease, but they only work for a short period of time. Patients still desperately need treatments that can either delay the onset of Alzheimer’s or slow its progress – and with the economic burden of dementia reaching £23bn a year, the need for these drugs is urgent. While this task may look daunting, now is not the time to falter. As a society, we simply cannot afford to.
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