Alzheimer’s Disease: Defusing The Bomb By 2025

Published in In Vivo Beyond Beta-Amyloid  The US FDA has approved six drugs to treat Alzheimer’s symptoms, all of which work by increasing the amount of neurotransmitters in the brain, helping nerve cells in the brain to communicate. These approved therapies are: Razadyne (galantamine), Exelon (rivastigmine), Aricept, Namenda,Namzaric (memantine + donepezil) and Cognex, which is no longer widely sold in the US. None of these drugs prevent or treat the cause of Alzheimer’s, nor do they slow progression of the disease. The leading theories being researched into the cause of Alzheimer’s that are currently guiding drug development processes are beta-amyloid, beta-secretase, tau protein, inflammation and insulin resistance. However, Susan Greenfield, PhD, CEO of Neuro-Bio Ltd., a company working on a new theory for the treatment of the root cause of Alzheimer’s, says that it’s time to reach for the higher hanging fruit. Greenfield published two research papers in Neuropharmacology in January and March 2016, studying a novel peptide found at raised levels in the brains of Alzheimer’s sufferers, which she believes to be the primary driver of neurodegeneration. Researchers at Neuro-Bio have now validated the theory for the continuing cycle of neuronal death that typifies Alzheimer’s and other neurodegenerative disorders such as Parkinson’s and motor neuron disease. The key driver is a 14 amino acid peptide (AChE peptide) that originates from acetylcholinesterase (AChE), an enzyme essential in breaking down a chemical messenger between neurons, but increasingly recognized as a signaling molecule with non-enzymatic functions. Whereas the existence of the AChE peptide and its link to neurodegeneration have been previously proposed in Greenfield’s work, these are the first reports of its detection in both human and rat brain and its actions in driving an Alzheimer’s-like biochemical profile. In summary, Greenfield views Alzheimer’s disease as an inappropriate form of development. “The reason damaged cells carry on degenerating is because they are trying to grow again. This is not normal for brain cells and this cell mobilization, while fantastic in an embryo, is unsuitable in a mature brain.” Greenfield says, “To the best of our knowledge it seems that although there are various drugs available to treat Alzheimer’s they are all variants on the same theme, principally targeting amyloid or tau. While our product is different we think we can tell the whole story of Alzheimer’s, and it seems to fit with the known clinical data. The complaints I have with the amyloid theory, is that while it is contributing to the disease, if that is all there was to it, you would have much wider damage with Alzheimer’s. So we know there is something more selective going on, there is something special about the brain cells that are initially lost,” she says. In the first paper, the damaging effects of either the AChE peptide or amyloid are shown to be blocked by a novel prototype drug (NBP-14), a cyclized form of the AChE peptide, being developed by Neuro-Bio. NBP-14 intercepts the action of the AChE peptide on the alpha-7 nicotinic receptor, which is found on the outer surface of neuronal cells. Greenfield wants to move this drug into Phase I trials within the next few years. “Currently, the prototype molecule we have is clumsy and clunky and not the ideal size to get into the brain. We have to get it right, we can’t have a drug that is good enough and neuroprotective, it has to be the best it can be,” she says. Neuro-Bio is now screening and defining the best molecule for further research in this area. It is also trying to develop a biomarker for the AChE peptide – one that it hopes to one day be able to measure in blood. Neuro-Bio was founded on angel investment but the company will be seeking venture capital funding and a partner, or multiple collaborators, to help move the product into human trials. “While I developed the idea, I am a research scientist and I have no experience of drug development,” Greenfield admits. “We need to collaborate with people with experience.” On the topic of funding in Alzheimer’s though, Greenfield notes that more money is needed for research. “If you look at the amount of money going into cancer and heart disease, it dwarfs the amount of money going into dementia and Alzheimer’s research. Clearly it has to become a higher priority,” she says. However, she notes that there is no point pouring more cash into the same old theories and that new approaches are needed. “Research like we are doing at Neuro-Bio, whether we are right or wrong, at least we are different so there is more chance of renewed success.”