At the end of November, a major roadblock in the road toward curing Alzheimer’s was announced. Eli Lilly, a major pharmaceutical company, failed to prove its latest drug, solanezumab, effective in a Phase 3 trial. While there are several other trials in the works for other solanezumab-based drugs from other companies, scientists are not getting their hopes up. Other trials of solanezumab have failed before, and according to Scientific American, this is typical, with more than 99% of Alzheimer’s drugs failing clinical trials after they were found to be nearly ineffectual. Many have been shown to be unable to stop the downward spiral of patients, even those with only mild dementia.
Anybody who knows an Alzheimer’s patient is aware of the potentially amazing implications if a cure could be found. The growing number of elderly people diagnosed with Alzheimer’s (and even the not so elderly, in the case of those with early-onset Alzheimer’s) whose ability to think, interact and function inexorably hurtles downhill, with little to no way of stopping the tide, is terrifying and saddening. The feelings of helplessness which affect the patients and their families in the face of the illness are now also being felt by the many medical researchers who are hitting dead ends as they try to figure out where the scientific community has been going wrong in their research and how they can get back on the right track.
Currently, conventional medical wisdom is that Alzheimer’s is caused by an accumulation of amyloid in the brain, which forms plaques that seem to inhibit cognitive function. Based on this idea, drugs like solanezumab, which are meant to attack the amyloid plaques in the brain, should be able to reverse this cognitive decline as the plaque decreases. If this had worked, people with developing dementia could theoretically have had their mental decline arrested or even reversed. The failure to achieve this, in the words of the incoming president and CEO of Eli Lilly, is “heartbreaking.”
With the failure of these drugs, scientists are wondering whether they have zeroed in on the right cause. Should they be looking in other directions for the root of the disease? Or, are they on the right track, but starting treatment too late to make any effect? Scientists are considering both of these approaches. Some maintain that Alzheimer’s has too many root causes, of which amyloid plaques are only one, with another popular potential culprit being tau tangles in the brain. Therefore, a drug solely targeting one symptom cannot be effective. Others say that they amyloid plaques are the cause, but even if drugs can effectively work against them, by the time the plaques have caused noticeable degeneration, they have been in place for many years and the damage is irreversible. Therefore, many researchers are trying to test drugs on people who do not yet have Alzheimer’s but are very likely to get it (such as people with a dominant Alzheimer’s gene) in order to see if early interception would allow the drug to work. This approach can be expensive and the potential negative side effects can be hard to justify, especially in a person who is still healthy. Other approaches include finding drugs with other attack mechanisms, upping the dosage, and making sure that the amyloid being attacked by the drug is the same one that is causing the disease.
While the setback is disheartening, it is also spurring scientists and researchers to explore several other potential medications and to think in new directions to find potential cures. At this point, it seems unlikely that the millions of people worldwide suffering from this devastating disease will (soon) be healed. However, as we look at the many new paths forward forged by this setback, we can hope and anticipate that perhaps one of them will, in the future, be the cure for Alzheimer’s.