Alzheimer’s Drug Fails, Amyloid Hypothesis Dubious

Eli Lilly’s Alzheimer’s drug, solanezumab, has failed to slow cognitive decline for Alzheimer’s patients. The drug was heralded as the pharmaceutical industry’s best answer to the hypothesis that amyloid plaque causes Alzheimer’s disease.

Turns out they were wrong. About the drug and the hypothesis.

Two human clinical trials failed

The two clinical (human) phase III studies, dubbed EXPEDITION and EXPEDITION2, were each 18 months long. The studies included a total of 2052 patients (1012 and 1040). Alzheimer’s disease patients were given 400 milligrams of the monoclonal antibody drug through infusions every four weeks, or a placebo.

Neither study showed positive results for the Alzheimer’s patients. The patients continued their cognitive decline with no change in progression. There was a subgroup of patients with mild Alzheimer’s that had slower progression compared to the placebo group. But this slower progression difference was small.

Eli Lilly’s own CEO, John Lechleiter, PhD, admitted failure. He said:

“The results of the solanezumab EXPEDITION3 trial were not what we had hoped for and we are disappointed for the millions of people waiting for a potential disease-modifying treatment for Alzheimer’s disease,”

Amyloid hypothesis doubted

For many years, a number of researchers proposed that Alzheimer’s disease is caused by the buildup of amyloid protein and plaque within the brain. This hypothesis has been questioned over the past few years. One startling reason: Many people with the amyloid plaque don’t get Alzheimer’s.

Nevertheless, the pharmaceutical industry has taken up the task of developing drugs that clear amyloid proteins from the brain. These include solanezumab, bapineuzumab, crenezumab and aducanumab among others. They portend to reduce amyloid proteins in the brain and cerebrospinal fluid.

They do this by attaching to the amyloid proteins that form the plaques. This is the specific mechanism of solanezumab. Once the drug attaches to the proteins, the bound proteins are removed from the cerebrospinal fluid. This was shown in animal studies, as the bound proteins were found in the plasma rather than the brain.

Yet even with this proven mechanism of action, the patients continued to get worse with the drug. Their Alzheimer’s disease continued to progress. This was proven using cognition testing called Alzheimer’s Disease Assessment Scale-Cognitive-14.

This puts the whole amyloid hypothesis in question.

Mayo Clinic physician David Knopman, MD, indicated the study’s implications for the amyloid hypothesis “are not good.” He added:

“The study was done as well as it could have been for very mild symptomatic people. The fact that clearing amyloid had no benefit is really very disappointing.”

“Very disappointing” means that billions of dollars of research funds have been wasted. Oh sure, we now know what Alzheimer’s disease isn’t. But what good is that?

Evidence to the contrary

Meanwhile, there is considerable evidence for the real causes and natural solutions to Alzheimer’s disease.

Billions have been spent investigating the erroneous hypothesis that a mysterious formation of an amyloid protein plaque causes Alzheimer’s. Or that some other mysterious biochemical is at fault – rather than what we eat or our lifestyles and environments.

So many scientists and research grants have ignored the obvious links between Alzheimer’s disease and poor diet choices, sleep issues, smoking, alcohol consumption and other health habits and environmental exposures.

Furthermore, so many sources of research funding have virtually ignored the research proving a number of natural herbs and plant extracts help prevent and even slow the progression of Alzheimer’s disease for those with the condition.

Despite this evidence, pharmaceutical companies would rather spend billions developing drugs to patent and charge patients outrageous sums of money. Welcome to healthcare in the 21st century.

Meanwhile, Alzheimer’s disease threatens over a third of adults as we enter our retirement years.

Find out the real facts about the causes and natural solutions to Alzheimer’s disease:

REFERENCES:

Eli Lilly Press Release. “Lilly Announces Top-Line Results of Solanezumab Phase 3 Clinical Trial” Nov. 23, 2016.

Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med. 2016 Jun 1;8(6):595-608. doi: 10.15252/emmm.201606210.

Amanatkar HR, Papagiannopoulos B, Grossberg GT. Analysis of recent failures of disease modifying therapies in Alzheimer’s disease suggesting a new methodology for future studies. Expert Rev Neurother. 2016 Jun 9:1-10.

Panza F, Seripa D, Solfrizzi V, Imbimbo BP, Lozupone M, Leo A, Sardone R, Gagliardi G, Lofano L, Creanza BC, Bisceglia P, Daniele A, Bellomo A, Greco A, Logroscino G. Emerging drugs to reduce abnormal β-amyloid protein in Alzheimer’s disease patients. Expert Opin Emerg Drugs. 2016 Oct 6:1-15.

Bouter Y, Lopez Noguerola JS, Tucholla P, Crespi GA, Parker MW, Wiltfang J, Miles LA, Bayer TA. Abeta targets of the biosimilar antibodies of Bapineuzumab,Crenezumab, Solanezumab in comparison to an antibody against N‑truncated Abeta insporadic Alzheimer disease cases and mouse models. Acta Neuropathol. 2015 Nov;130(5):713-29.

Fiore K. Amyloid Drug Fails Major Trial. MedPage Today. Nov. 23, 2016.

Watt AD, Crespi GA, Down RA, Ascher DB, Gunn A, Perez KA, McLean CA, Villemagne VL, Parker MW, Barnham KJ, Miles LA. Do current therapeutic anti-Aβantibodies for Alzheimer’s disease engage the target? Acta Neuropathol. 2014;127(6):803-10. doi: 10.1007/s00401-014-1290-2.

Adams, C. Holistic Remedies for Alzheimer’s: Natural Strategies to Avoid or Combat Dementia. Logical Books, 2016.