Remarkably,
Alzheimer’s research has continued to advance in a year that has
been troubled by great financial instability and The John Douglas French Alzheimer’s Foundation’s support for
important research into the diagnosis and basic mechanisms associated with Alzheimer’s disease remains steady and
powerful. Funding for creative Assistant Professors at UCLA, UCSF and USC Keck
School of Medicine is generating exciting new findings related to
neuroimaging, gene expression, protein structure and drug discovery for
Alzheimer’s disease and related disorders.
Several
types of new medications are currently being explored in clinical trials for Alzheimer’s disease. One major group of
compounds appears to work
by diminishing the concentration of the extracellular beta-amyloid protein within the
brain, while the other chief approach targets the intracellular protein tau.
Some have suggested that the intensity of the arguments
between the Beta-amyloid proponents (abbreviated Bap, and given the acronym Baptists) and tau proponents (Taoists) has
reached the intensity of religious wars. We all hope that
both of these research groups will
be proven correct
because new therapies for Alzheimer’s disease are desperately needed.
Monoclonal
anti
bodies or vaccines that target the A-β42 protein work
by increasing the clearance of this protein from the brain. Another way of diminishing this protein is to give compounds that
diminish the production of A-β42 (so-called secretases). Both of these
approaches are formally testing the “amyloid hypothesis” suggesting that
Alzheimer’s disease is caused
by the abnormal accumulation of A-β42. Whether or not the toxicities of these
medications will exceed their benefits remains unknown, but
by the end of 2009 important new answers will emerge either supporting or
refuting the idea that diminishing A-β42 is a viable treatment for Alzheimer’s disease.
In
parallel but distinctive efforts, stabilizing or eliminating the intracellular
tau protein is being attempted. This idea is supported
by the finding that diminishing tau protects animals programmed to overproduce
A-β42 from its toxic effects. The tau trials are just
beginning and no definitive answers are expected in 2009,
but even if the A-β42 approaches fail, anti-tau compounds may still work.
Finally, much to the surprise of many scientists, a compound called Dimebon, used for many decades in Russia, has shown promise in a large recently
completed European trial. Dimebon is now moving into what is called a phase III trial in the
United States
which could lead to FDA approval for this medication within the next several
years. Stay tuned!
Other
noteworthy developments have emerged in Alzheimer’s disease related to
diagnosis and drug screening. The discovery
by Shinya Yamanaka (jointly
based in Kyoto, Japan and at UCSF’s Gladstone Institute) that human skin
cells could
be transformed into stem cells and then converted into neurons has electrified
the scientific community. Whether these skin cells can ever
be a viable therapy remains in doubt,
but there is great excitement that these person-specific cells could
be used to screen for new medications, increasing the likelihood that our
screening procedures for new compounds will translate more effectively into
real treatments. In the area of diagnosis, new amyloid
binding imaging agents are being developed as a simple and powerful way to diagnose Alzheimer’s disease
in the very earliest stages, in some instances even before the illness has manifested clinically.
Your leadership and generosity is moving us all closer to the day when
Alzheimer’s disease is a distant memory, and we all maintain the precious
memories that are taken away with this terrible illness. Our founder Dorothy Kirsten French reminded us to, “Forget not
those who cannot remember.”
