Small molecule with a potentially big impact on Alzheimer's
Despite decades of research, a cure for Alzheimer's remains elusive. But work conducted in Europe suggests that the onset and progression of the disease could be prevented or slowed down by a molecule that mimics the activity of a critical protein (neurotrophin) affecting neurons in the brain.
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Alzheimer’s current affects around 30 million people worldwide, and the figure is expected to rise as the population ages. The research, conducted in the EU-funded StressAmyloidCascade project, has demonstrated that drugs administered through the blood stream before the onset of Alzheimer-like symptoms in mice, can prevent age-associated cognitive impairments. The same treatment, based on a small-molecule synthetic compound called 7,8-DHF, also shows promise in slowing or even reversing cognitive decline after Alzheimer’s symptoms start to appear.
“Most current approaches to treating Alzheimer’s address the late stages of the disease when the pathology is hard to reverse and significant damage to mental health has already occurred. We therefore sought to identify windows during which therapeutic strategies to prevent or delay the onset of the disease would work,” explains Raul Delgado Morales, a Marie Curie fellow who conducted the research at the Max Planck Society for the Advancement of Science in Germany.
The StressAmyloidCascade team carried out the research using young adult mice genetically engineered to over-produce amyloid-beta (Abeta peptide), a compound that is strongly implicated in Alzheimer’s pathology.
Preventing and delaying cognitive impairment
While untreated mice showed obvious cognitive decline after five months, those treated with 7,8-DHF showed no impairments in spatial memory and had reduced levels of the neuron-endangering peptide Abeta in the hippocampus and frontal cortex – two brain areas involved in memory. In addition, when administration of 7,8-DHF began while the mice were middle-aged and Alzheimer’s symptoms had started to appear, the treatment slowed the cognitive decline.
“We already know of many potential drug targets, but drug development is hampered by not knowing how to target [them] effectively. 7,8-DHF is a small molecule that can easily enter the brain, does not have known side effects and is relatively cheap,” explains Osborne Almeida, the project coordinator. “Obviously, using mice to study a complex human disease has many limitations, but such studies are needed to demonstrate efficacy and examine pharmacology and toxicity, only then would limited human trials be ethically justified. At present, we have only studied a prototype drug: many more tests will be required, and further developments will depend on chemists who can design molecules with similar or better properties.”
The project team are seeking funding to continue their work and expand collaboration with scientists in other disciplines, focusing most immediately on identifying the exact mechanisms through which 7,8-DHF achieves its effects.
Though much more research is required, the achievements so far of StressAmyloidCascade nonetheless constitute an important contribution to Alzheimer’s research and could guide the development of new preventive treatments in the future, helping to lower the incidence of a disease that currently affects around 30 million people worldwide.
As the world’s population ages, that figure is expected to rise to more than 60 million by 2030 and 115 million by 2050, resulting in hundreds of billions of euros in costs for healthcare systems and an incalculable human cost in terms of the individual suffering of patients and their families.
“Our work represents a small, but committed [contribution] towards global efforts to fight Alzheimer’s,” the project coordinator says. “It places emphasis on the need for strategies that will prevent, delay or slow down disease onset and progression, improving quality of life for people who would otherwise become Alzheimer’s victims.”