Hillblom Foundation meeting report

I spent the early part of this week at the annual scientific meeting of the Larry L. Hillblom Foundation, the folks who are kind enough to pay my salary. It was an intimate conference, with fewer than a hundred attendees. Most of us are receiving postdoctoral fellowships from the LLHF, but there were also young faculty with startup money and senior people with network grants (these last were overrepresented in the talks, as might be expected).

The LLHF, to quote its own mission statement,

… has determined that its initial medical research priorities should be in the areas of diabetes mellitus and diseases associated with aging.

So most of the scholars represented were studying either some aspect of pancreatic islet biology or a neurodegenerative disease. Basic biologists of aging per se were fewer and further between, though there were a couple of excellent worm talks from Andy Dillin from the Salk, and Laura Mitic from the Kenyon lab at UCSF.

Probably the most exciting talk at the meeting was from UC-Irvine’s Charlie Glabe, whose lab is developing antibodies targeted at amyloid Aß oligomers (increasingly, the form considered likely to be the primary pathologic species in Alzheimer’s disease). The Glabe lab and their collaborators have created a panel of conformation-specific antibodies that have potential value in passive immunization against toxic forms of Aß.

Passive immunization, in which a patient is given the antibody directly, rather than immunized against the toxic molecule and left to develop their own antibodies, seems to be the main direction for immunologically based AD treatments, and for good reasons: Humanized monoclonal antibodies can be evaluated for their specificity and cross-reactivity before introduction into a patient, allowing a controlled immune response with minimal side effects. Perhaps more importantly given the failures of the Elan trials back in 2001, externally synthesized antibodies can be withdrawn at any time in the event that life-threatening complications arise — in other words, the extent of the immune response is under the control of the clinician, rather than left up to the patient’s own immune system.

Despite the high specificity I touted in the previous paragraph, anti-oligomer antibodies do cross-react — with other toxic protein oligomers. For example, several of Glabe’s anti-Aß monoclonals also recognize IAPP (islet amyloid polypeptide), an aggregate thought to be involved in the pathogenesis of type II diabetes. It remains to be seen whether anti-oligomer immune therapy can kill multiple birds with one stone, but the possibilities are certainly intriguing.