Kirsten Holst
Patients with Alzheimer’s disease will probably be treated with a cocktail of disease-modifying drugs in the future, a neuroscientist told the annual University College London school of pharmacy lecture at the Royal Society in central London on 12 January 2016.
John Hardy, a professor of neuroscience at UCL, said that several drugs are likely to be used to slow down the progression of Alzheimer’s disease in a similar way to the treatment of other complex conditions such as diabetes.
Recent genetic findings have pointed to three different mechanisms being involved in the pathology of the disease, Hardy said. The first causes amyloid protein to build up in the brain, leading to the development of amyloid plaques. A more recently discovered set of genes determines how the brain breaks down amyloid, and a third set of genes is involved in brain cholesterol metabolism. But researchers “don’t know how it fits in precisely”, he said.
Predicting how this genetic information could be used to inform drug treatment, Hardy suggested that a monoclonal antibody directed against amyloid might be used in combination with a drug that helps the brain “digest” amyloid and a drug that alters brain cholesterol in way that is helpful for the clearance of amyloid. “In the longer run [we] will head towards polypharmacy like we have with other diseases,” he said.
There are two drugs in clinical trials that Hardy said “all of us in the field are very excited about”: solanezumab, which is being developed by Eli Lilly; and aducanumab, being developed by Biogen. Both are monoclonal antibodies that help the brain clear amyloid. Researchers are due to report results in around 18 months. “If they are successful, it tells us immediately we are on the right road and will lead to a massive investment by industry to develop drugs that target amyloid in other ways,” he explained.
However, Hardy cautioned against hoping that drugs will be able to reverse the effects of Alzheimer’s disease, saying that this is “a very difficult thing to solve”.
“I think we’ll see a slowing of the disease process, not genuine reversal,” he added.
Alzheimer’s disease accounts for about 60% of cases of dementia. Since 1980, there has been a 20% drop in dementia incidence, which could be the result of improved lifestyle habits. Hardy explained that, in light of the recent genetic findings, this drop in incidence may also be partly because “we are better at controlling cholesterol”. However, he also highlighted that lifestyle changes will not prevent the majority of dementia cases and that new drugs are vital to treat the disease.
