“Alzheimer’s disease is the only one of the top 10 causes of death in America that cannot be prevented, cured or even slowed down once it begins. Most of the drugs that have been developed have either failed or only provide modest improvement of the symptoms. So finding a better pathway for these potential therapeutics is critical,” says Dr. David Teplow, the principal investigator of the NIH-sponsored Alzheimer’s Disease Research Center at UCLA.
Current Alzheimer's drugs aim to reduce the amyloid plaques (sticky deposits) that build up in the brain and interfere with the messages that are transmitted between neurons (brain cells). The amyloid plaques are the visual trademark of Alzheimer’s, and are made of long fibers of a protein called Amyloid β or Aβ. Recent studies, however, suggest that the real culprit behind Alzheimer's may be small Aβ clumps called oligomers that appear in the brain years before plaques develop.
One of several new theories about how Alzheimer’s develops
In unraveling oligomers' molecular structure, UCLA scientists discovered that Aβ has a vastly different organization in oligomers than in amyloid plaques. Their finding could shed light on why Alzheimer's drugs designed to seek out amyloid plaques produce zero effect on oligomers. The UCLA study suggests that recent experimental Alzheimer's drugs failed in clinical trials because they zero in on plaques and do not work on oligomers. Future studies on oligomers will help speed the development of new drugs specifically aiming at Aβ oligomers.
These oligomers now are seen to be forming at or near the neurons in the brain responsible for the neural communication that enables acquisition of new information and creation of memory. The science of all of this is complicated and rapidly evolving, but the essence is that the focus of the cause of the disease has moved for the most part from the plaques to the formulation of the Abeta peptide itself and its coalescing into the more toxic oligomers.
Teplow and his colleagues are working to find the most relevant target for the development of drugs to fight Alzheimer’s. Dr. Teplow explains that the Abeta protein is composed of a sequence of amino acids, much like “a pearl necklace composed of 20 different combinations of different colors of pearl.” One form of Abeta, Abeta40, has 40 amino acids, while a second form, Abeta42, has two extra amino acids at one end. Abeta42 has long been thought to be the toxic form of Abeta. But until now, no one has understood how the simple addition of two amino acids made it so much more toxic then Abeta40.
Current Alzheimer’s drugs
1. Aricept® (donepezil)
2. Razadyne® (galantamine)
3. Exelon® (rivastigmine)
Hopeful drugs in the pipeline
1. NitroNamenda is the first experimental drug to boost brain synapses lost in Alzheimer’s disease. It combines two FDA-approved drugs: nitroglycerine and memantine (Namenda®). NitroMemantine brings the number of synapses all the way back to normal within a few months of treatment in mouse models of Alzheimer’s disease. Hopefully, it won’t take long to get FDA approval.
2. Targretin (bexarotene) is a cancer drug that erased beta amyloid within hours from the brains of mice with simulated Alzheimer’s disease. It has not been FDA approved for Alzheimer’s and it currently costs about $1,156 for 30 75 mg. capsules. It will have to go through several rounds of clinical trials before it is approved for Alzheimer’s, and this will take years.
Please subscribe today to receive updates on Alzheimer’s news, care and drugs, and information on how caregivers can reduce stress and burnout.
1. University of California, Los Angeles (UCLA), Health Sciences (2013, July Discovery sheds light on why Alzheimer's drugs rarely help.
2. http://curealz.org/2010/04/why-don%E2%80%99t-drugs-work © 2005-2013 Cure Alzheimer’s Fund.
3. Sanford-Burnham Medical Research Institute