Leucadia Therapeutics is a startup company focused on Alzheimer's disease, noteworthy for being one of the few ventures to depart from the orthodoxy of immunotherapy to clear amyloid and tau protein aggregates. The Leucadia staff are working on the establishment of a faster and cheaper path to an effective therapy for Alzheimer's that nonetheless still addresses the deeper causes of the condition.

Leaving the mainstream is perhaps more of a challenge in the Alzheimer's research community than elsewhere; the US National Institute on Aging has for years been primarily an Alzheimer's concern, and the biggest of Big Pharma entities have made equally large investments in the field over that same period of time. As a result there is a great deal of institutional inertia to continue to push forward with large and costly amyloid clearance strategies that are only incremental improvements on those that have failed by the dozen in the past. Publicly advocating any other path can have a negative impact on career prospects when embedded in such a large and structured system. However, going on for two decades in to these efforts, and with no practical therapy yet to show for the billions spent, the Alzheimer's heretics are starting to become more organized and influential.

It is undeniably the case that protein aggregates of amyloid and tau are important in Alzheimer's, and if they were removed safely and efficiently, patients would benefit. But these forms of metabolic waste are not the whole story; how is it that their presence only grows in the aging brain? Is some combination of declining immune function and persistent microbial infection a significant source of protein aggregates, for example? The evidence for that hypothesis is quite compelling. And in the case of Leucadia's work, are protein aggregates observed in the aged brain there due to a failure of drainage systems? The cerebrospinal fluid is thought to carry these aggregates away for disposal elsewhere in the body, but the pathways used fail with age. Thus the slow buildup of amyloid and tau with age might be thought of as a progressive failure of clearance of these waste products, a structural and fluid flow problem, rather than a cellular problem of greater production.

This is an attractive hypothesis, not least because testing it should be a comparatively low-cost, rapid effort - very far removed from the vast expense of current amyloid clearance approaches. Leucadia is the company formed to carry this initiative forward, now that the research and evidence gathered to date has reached the point of making that leap. The Methuselah Fund and a number of other angels and organizations have invested in Leucadia Therapeutics to date, Fight Aging! among them. Since the latest round of funding is now complete, I recently had the chance to talk to founder Doug Ethell and ask some questions about the company and the approach to Alzheimer's disease.