The study, partly sponsored by the University of Birmingham and by Roche Pharmaceuticals, reports the dysregulation of the pathways regulated by the mammalian target of rapamycin (mTOR) in the brain before the development of pathology, amyloid plaques and neurofibrillary tangles and shows that the dysfunction of this pathway may be a risk factor for Alzheimer’s disease. It appears that the dysfunction of the mTOR pathway is a constitutional characteristic of an individual and can be detected in peripheral lymphocytes, providing a potential practical test that can be performed on standard blood samples. The assay is based on the measurement of rapamycin response in lymphocytes. The publication reports that the technology was capable of distinguishing samples from age-matched control subjects from those of Alzheimer’s patients with high sensitivity and specificity. The reported accuracy of > 83% increased further with the inclusion of ApoE4 status.
Cytox's patented technology is based on discoveries made by the company's scientific founder, Dr. Zsuzsanna Nagy, demonstrating cell cycle-related factors are associated with the risk of developing Alzheimer’s disease. The cell cycle hypothesis postulates that the dysfunction of pathways associated with cell division in neurones allows these cells to (abnormally) progress to the late stages of the cell cycle, where they produce the building blocks of Alzheimer’s pathology, plaques and tangles.
Professor Karl Herrup of Hong Kong University of Science and Technology and a leading researcher in the field of cell cycle regulation and Alzheimer's disease said of the published data: "This is important work that deserves significant attention from the field. The authors make a compelling case for the potential of their new approach. If validated in larger samples, their finding is exciting as it points the way towards the use of different manifestations of the Alzheimer's disease process - the activity of the mTOR network in this case - as a sensitive and specific assay for disease risk." Professor Herrup added that "as the authors themselves point out, there is much to do, but this is certainly an approach worth keeping an eye on".
The assay technology has now been tested in close to 300 subjects in three clinical studies. Cytox will be seeking to accredit a commercial assay service for the phenoTOR assay in a new laboratory based in Manchester.
It is believed that the assay will be potentially useful to pharmaceutical industry clients, offering a way of stratifying patients in therapeutic trials. Trials are planned to further validate the test for commercial use as part of the clinical management of patients suffering from cognitive deficit.
1. Yates SC, Zafar A, Hubbard P et al. (2013) Dysfunction of the mTOR pathway is a risk factor for Alzheimer’s disease. Acta Neuropathologica Communications online