After the recent failures of two Alzheimer’s drugs that target amyloid beta plaques, many have questioned the approach. But new data released in October shows promise for the amyloid hypothesis, provided plaque-targeting drugs are applied early in the disease process.
Most therapies for Alzheimer’s disease (AD) focus on reversing the buildup of amyloid beta plaques–malformed protein fragments that amass in the brain, killing brain cells and severing connections. But after two large-scale trials failed to show the approach significantly affected disease symptoms, companies have started to wonder if the strategy is flawed. Some Big Pharmas, seeking returns on investments, are asking if Alzheimer’s is too much of a gamble altogether.
In August, Johnson & Johnson and Pfizer discovered that their plaque-targeting drug, bapineuzumab, showed no benefit in those with Alzheimer’s. In the same month, Eli Lilly & Co. found that solanezumab, a similar drug, showed no effect in slowing memory decline in those with the disease.
Both drugs were designed to target destructive amyloid plaques, widely believed to play a key role in the pathogenesis of Alzheimer’s. While many have questioned the amyloid theory following the drug’s failures, data from the most recent Eli Lilly trial shows promise for such plaque-targeting medications, provided they are administered before the plaques have accumulated significantly.
Eli Lilly’s trials showed solanezumab failed to slow memory decline in those with mild to moderate Alzheimer’s, but new data published in October proved it actually slowed mental decline in those with a mild form of the disease–42% of patients over 18 months. Eli Lilly and the Alzheimer’s Disease Cooperative Study analyzed the data, confirming solanezumab slowed memory loss in those still in the early stages of Alzheimer’s. It also slowed the loss of functional abilities, such as bathing and dressing.
The drug works by preventing the formation of amyloid-β before it turns into plaques. The new data may reinvigorate the development of plaque-targeting medications, keeping in mind they may work best when administered many years before symptoms occur, when protein deposits begin accumulating.
But this approach will require powerful diagnostic tools, tools which can identify the memory-robbing condition 10 or even 15 years early. Such technologies could identify disease pathology far in advance, so that plaque-targeting drugs could prevent neuronal loss.
While some drug companies will remain spooked by this summer’s data, most probably won’t lose sight of the fact that 36 million people now suffer from Alzheimer’s and that by 2050 one out of 85 people in the world will have the disease, representing a market of $10 billion or more.