The Leucadia Therapeutics principals and staff are working towards the prevention of Alzheimer's disease. Unlike most other initiatives in the space, their work is based on a novel understanding of the way in which reduced drainage of cerebrospinal fluid gives rise to Alzheimer's disease and potentially other neurodegenerative conditions. These conditions are characterized by rising levels of protein aggregates and other forms of molecular waste in the brain. This leads to toxicity to neurons, as well as to chronic inflammation due to the reactions of immune cells and other cells in brain tissue.
Cerebrospinal fluid drainage from the brain into the body is one of the ways in which these forms of waste are removed from the brain, keeping levels more manageable. As drainage falters due to age-related changes to the tissues involved, ever more molecular waste is trapped in the brain. Alzheimer's disease is one of the results. Leucadia researchers have in recent years used ferrets to show that surgically blocking cerebrospinal fluid drainage paths provokes early increases in protein aggregation, and then consequent neurodegeneration and cognitive decline.
Leucadia is one of the many stories in the anti-aging research and development community that in some way involves the Methuselah Foundation. Early work at Leucadia was funded by the foundation, and it was a conversation with Dave Gobel of the Methuselah Foundation at a scientific conference that convinced Doug Ethell, the Leucadia founder, to take his work out of academia and start down the road to human clinical trials. The company will in the next few years implant valve devices into patients to restore a measured flow of cerebrospinal fluid through the most important drainage pathway, and hopefully thereby definitely proof that Alzheimer's disease can be indefinitely postponed via this approach.
For the past 25 years, Alzheimer's disease researchers have viewed plaques and tangles pathology as the cause of Alzheimer's, which has led to an unbroken string of failed clinical trials. In 2014, neuroscientist Doug Ethell published a new hypothesis about the trigger for Alzheimer's and related dementias. In 2015, he founded Leucadia Therapeutics to develop a therapy based on his hypothesis. Leucadia's research has shown that plaques and tangles are effects of a more serious underlying condition that triggers the formation of those pathological features.
The cribriform plate is a porous bony structure located in the roof of the nasal cavity. The plate contains two deep pockets called fossa and many holes called olfactory foramina. Olfactory nerves that transmit the sense of smell pass through these holes. The cribriform plate is an outflow route the brain uses to clear out waste in cerebrospinal fluid (CSF). About half a liter of CSF is produced by the brain each day, but only about 1/20 of it drains through the cribriform plate. However, that small amount of CSF is responsible for clearing brain regions that are critical for making new memories and orienting us in the world. As humans age, the cribriform plate becomes ossified and less porous. The small holes close up and restrict the flow of cerebrospinal fluid. As less and less of this fluid is drained out of the brain, waste and toxins accumulate in the upstream brain regions responsible for memory. These waste-products form a slough (an area of dead tissue) where plaques form and neurons form tangles - two key hallmarks of Alzheimer's disease. Ethell's research indicates that Alzheimer's disease pathology result from reductions in cerebrospinal fluid drainage across the cribriform plate.
Leucadia Therapeutics is preparing for a clinical trial in 2022 that will use an implantable device to restore CSF drainage across the cribriform plate. With increasing life-expectancy, Dr. Ethell believes his device will become as common as a pacemaker. This well-founded approach should reverse early mild cognitive impairment and prevent Alzheimer's disease from occurring at all.