Research into a previously ignored area of the brain has revealed a molecule that could be a key driver of Alzheimer’s. Not only has this neurotoxic chemical been identified, but so has a drug to combat it. It’s a nasal spray that’s showing very exciting results in preliminary research. Here’s the story…
For three decades the focus of Alzheimer’s research has been on clearing amyloid plaques from the brain. The result of all of this research is summed up by Dr. Gregory Cole, Professor of Neurology at UCLA: “I’ve specialized in Alzheimer’s disease research and worked for real treatments in UCLA’s Alzheimer’s program since 1994. Along with my colleagues around the world, we’ve all witnessed hundreds of failed drug trials based on existing theories and we are ready for truly new approaches.”
He and his colleagues, in collaboration with scientists from the United Kingdom, have been working on one such new approach, and believe the development of this drug called NBP14 could reap rich rewards.
A Jekyll and Hyde Dementia-Triggering Molecule
Not all brain cells are the same. Those that are vulnerable to neurodegeneration come from a specific area of the brain called the isodendritic core (IC). These vulnerable neurons are evident even at four weeks gestation.
In 2015 scientists from the University of California San Francisco (UCSF) wrote that “neurons of the IC system show neurofibrillary tangles in the earliest stages of Alzheimer’s.” They suggested that “the IC network represents a unique candidate for viable therapeutic intervention and should become a high priority for research in Alzheimer’s.”
This brain chemical T14 triggers the growth and development of embryonic IC cells, but they retain their ability to instigate growth even in adulthood. It was only identified 20 years ago.
Baroness Susan Greenfield, neuroscientist and CEO of Neuro-Bio, a spin-off from Oxford University that developed the drug NBP14, describes T14 as a “Jekyll and Hyde molecule.”
That’s because it has beneficial effects on the growth and development of the fetal brain but becomes toxic if this process happens inappropriately in later life.
T14 could be triggered by a blow to the head, a restriction to the brain’s blood supply, an inadequate level of antioxidants to mop up free radicals, or some other mechanism. If it isn’t stopped it will continue uninterrupted and spread to other areas of the brain to cause the familiar symptoms of Alzheimer’s up to two decades later.
But T14 can be stopped dead in its tracks thanks to NBP14. The latest study lends support to scientists who believe T14 could be at the very heart of the degenerative process.
Normal Cognition Restored
Mice engineered to develop Alzheimer’s were treated with a nasal spray containing NBP14 for six weeks. This resulted in a marked decrease in amyloid plaques. After 14 weeks their cognitive performance improved to the same level as normal mice.
Baroness Greenfield believes their approach is a genuine breakthrough for three reasons:
- It identifies a neurodegenerative process that occurs before amyloid gets involved.
- It accounts for why some neurons are selectively vulnerable to neurodegeneration and not others.
- And, because the same process is involved, it also explains why Alzheimer’s disease frequently occurs alongside Parkinson’s disease.
Baroness Greenfield said, “By using basic neuroscientific knowledge we have identified what we believe is an underlying mechanism driving Alzheimer’s. Our recent efficacy study in mouse models further validates previous work describing an erstwhile unidentified process in neurodegeneration and offers very exciting prospects for treating the disease in humans.”
Professor Paul L. Herrling, a Non-Executive Director at Neuro-Bio, added, “The results consistently indicate that NBP14 might interfere with the neurotoxic process that leads to neuronal degeneration in Alzheimer’s. This work has very exciting implications for treating Alzheimer’s because it is based on a strong scientific theory that hasn’t yet been applied to treatment of the disease.”
A Future Without Alzheimer’s?
The vision for the future, outlined by Baroness Greenfield, is to develop a blood test for T14 that could be given routinely at the doctor’s office.
If the test identifies the beginnings of neurodegeneration, the patient would be prescribed a nasal spray that would put a stop to the disease process, so memory loss never develops.
Those already showing signs of memory impairment or already diagnosed with Alzheimer’s would also be treated with the spray. In this way the cognitive impairment, at the very least, wouldn’t get any worse.
This dream is some way off, however. The first phase 1 human trial of this new nasal spray is not expected to begin until the latter part of 2024. I will keep you posted.