Biostatistical and Experimental Design Assessment of Research on Tau Tangle Targeting for Alzheimer’s Disease

Implications: Slowing the progression of Alzheimer's disease by attacking tau tangles is a novel idea that should be considered a viable treatment alternative, especially in light of the failings of some recent beta-amyloid treatment strategies (e.g., Flurizan).   At the 2008 International Conference on Alzheimer's Disease (ICAD 2008), Dr. Claude Wischik (Univ. of Aberdeen and TauRx Pharmaceuticals) and colleagues gave positive research reports on treatments developed to target and dissolve the tau tangle protein complex, including the first report of an international randomized Phase II clinical trial of Rember™.   We performed a comprehensive biostatistical and experimental design assessment of the pre-clinical and clinical research reported by Dr. Wischik and colleagues at ICAD 2008, to see if the evidence for tau tangle targeting has early scientific validity.

Analysis: A novel therapeutic target for treatment of Alzheimer’s disease by dissolving tau tangle protein complex has been developed and tested. The pre-clinical and clinical data analyses suggest biological plausibility of the approach and preliminary statistical improvement in treated mice and human subjects. The trio of presentations discussed here, as well as other previous publications from this group, makes a compelling story for the likely success of Tau aggregate inhibitors and dissolvers.

From the 2008 International Conference on Alzheimer’s Disease, three significant findings were reported related to tau tangle protein complex targeting:  

1. The drug MTC serves as a Tau Aggregation inhibitor in vivo both in a cellular assay and in two distinct transgenic mouse models. In the mice, brief treatment with MTC produced a reversal of Tau pathology. (Presentation O1-06-04)  

2. Transgenic mice expressing high levels of human tau showed significant cognitive improvement when treated with MTC. MTC had no effect on cognitive ability in wild-type mice. (Presentation P2-383)  

3. Results of a Phase II placebo-controlled clinical trial (N = 332) showed significant improvements in MTC treated subjects in several key measures, including an improvement, relative to placebo, of -5.4 on the ADAS-cog scale at 24 weeks (p = 0.0208). (Presentation O3-04-07)


From a biostatistical point of view, there appear to be no problems with their experimental designs or statistical analyses, and in fact this body of work suggests a focused and scientifically strong effort.

If future clinical trials show the same trends, then Rember™ has the potential to be the first of a new class of important drugs for treating Alzheimer’s disease.

For further information about our biostatistical assessment of these and other studies, please contact your GLG representative to schedule an individual consult.