Promising Alzheimer’s drug fails in large trial

An experimental Alzheimer’s drug called Solanezumab that previously showed promise in its ability to slow the memory deterioration observed in Alzheimer’s patients recently failed in clinical trials.

This was a huge disappointment for many patients hoping for an effective treatment option. Furthermore since solanezumab targeted the buildup of amyloid proteins, its failure challenges aspects of our current understanding of Alzheimer’s.

Alzheimer’s disease is a chronic, progressive neurodegenerative disease that causes 60 to 70 percent of dementia cases. In advanced stages of the disease, patients often have problems with speech, become disoriented easily, have mood swings and often withdraw from family and society. The cause of Alzheimer’s is still not fully understood.

Researchers suggest that approximately 70 percent of the risk is genetic, with multiple genes having responsibility in the onset of the disease.

The current leading theory on the pathology of Alzheimer’s revolves around the idea that proteins, specifically amyloid-beta and tau, abnormally group together in the brain.

When these protein plaques bind to the surface of neurons and change the structure of the neuron on its signaling hub known as the synapse. This disrupts the ability of neurons to communicate with each other.

The failure of Solenezumab sheds light on how difficult it is to treat patients even with a mild form of dementia. This suggests the idea that by the time we see symptoms of dementia, it may be too late. Extensive damage could have already occurred in the brain by the time patients experience symptoms.

“Once you see amyloid on a scan, it’s probably been there for decades,” Dr. Samuel Gandy, an Alzheimer’s researcher at Mount Sinai Hospital told The New York Times. “I’m worried and have been worried that that’s just too late, I think it has a better chance of working much earlier.”

Solanezumab had previously failed in two clinical trials involving patients with mild or moderate Alzheimer’s disease.

However, the data from the trials suggested that the drug did have an effect on a subset of patients with a mild form of the disease, which is why Eli Lilly, a pharmaceutical company, decided to pursue an additional trial.

Dr. Eric Reiman, executive director of the Banner Alzheimer’s Institute, is leading a project focused on preventing the disease. He is working with members of a large extended family in Colombia who do not have symptoms but have genetic mutations that put them at risk of developing Alzheimer’s disease.

Dr. Reiman says Eli Lilly’s trial results raises questions about whether the dose was high enough, whether the researchers developed the drug to target the right form of amyloid and whether the patients used for the trial were too late in the progression of the disease. The results also suggest that the treatment of Alzheimer’s will require multiple drugs that attack multiple aspects of the development of Alzheimer’s.

In the end the failure of Solanezumab in this trial does not kill the leading theory of Alzheimer’s, as Solanezumab and other drugs based on the “amyloid hypothesis” are still being tested in large clinical trials.