We already know Eli Lilly’s big bet on Alzheimer’s disease didn’t work. But a deep dive into just how it failed has provided a bit of encouragement to Biogen and the many companies still hoping to succeed where their rival fell short.
Lilly’s treatment, solanezumab, had no significant effect on the buildup of toxic brain plaques believed by many to be responsible for Alzheimer’s neuron-destroying effects. The company had already disclosed that the treatment failed to improve patients’ cognition and function, but the new data, released Thursday night, shed some important light on the underlying biology.
Here’s why it matters: Lilly’s therapy is among many designed to treat Alzheimer’s by clearing away brain deposits of a protein called beta-amyloid. Doing so, the thinking goes, can at least delay the progression of the memory-robbing disease. Because Lilly’s failed treatment didn’t have a marked effect on those deposits, the so-called amyloid hypothesis lives to fight another day.
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It appears to me that Biogen is engaging in a type of bait and switch unless the company simply does not have cognitive data ready for its 24 month study or it is going to release it tomorrow. Removal of amyloid plaques is not a substitute for changes in cognition and functions of daily living. At six months, there was no significant difference in cognition between the placebo group and any dose of the aducanumab group. At 54 weeks, there was no significant difference between the 1mg. group and the 6mg. group versus placebo.
The greatest apparent slowing of decline at 54 weeks was with 10 mg’s but this was also the group with the highest drop outs due in part to serious adverse affects such as brain swelling. Many of these participants had the Apoe4 gene who usually progress most rapidly during the early stages of Alzheimer’s disease. Some journalists have accused Biogen of carrying the last observed results forward for drop outs, but even if this was not the case, more fast progressing patients were in the placebo group that in the higher doses of the aducanumab group. Only the 3 mg. group may have actually had some slowing down of the progression of the disease at 54 weeks and outside of the 1 mg. group this was the group that had the fewest amyloid plaques removed.
Amyloid plaques in and around neurons do not cause Alzheimer’s disease. Healthy individuals can have high levels of plaques in their brain and not have Alzheimer’s disease. Neuronal plaques may actually be neuroprotective in that the inhibit the development of plaques in and around blood vessels (which can cause problems including brain swelling, microbleeds, and declines in cognition), entomb copper and plaques which limits the production of the oxidant hydrogen peroxide, and “replace” more toxic amyloid oligomers. As long as other oxidants such as peroxynitrite are being scavenged, there is no damage being done to the brain by amyloid in any form.
Aducanumab also removes amyloid oligomers but oligomers are only one of many factors that can contribute to cognitive decline during the early stages of Alzheimer’s disease. Amyloid oligomers cause oxidative damage to receptors (g protein-coupled receptors) that are in turn damaged by oxidation. Other g protein-coupled receptors damaged by oxidation affect the retrieval of short-term memory, sleep, mood, smell, alertness, and social recognition.
Drugs like ANAVEX 2-73 that limit oxidative stress and natural products such as CBD oil, panax ginseng, and various essential oils through aromatherapy that lead to the scavenging of peroxynitrite and the partial reversal of nitro-oxidative damage are likely the keys to treating Alzheimer’s disease. All other approaches are probably fool’s errands.
I would appreciate some evidence supporting your last paragraph.
Thank you.