Mindset has a unique platform for lead drug candidate selection and optimization which is based on characterizing drug effects in transgenic mouse models of Alzheimer’s disease.

These models, which have been created by leading scientists to reproduce key features of Alzheimer’s disease, are used to test drug effects on amyloid burden and its associated neuropathology, including markers of oxidative stress and inflammation, abnormal changes in cell structure, and neuronal growth as well as effects on cognitive impairment.

The behavioral abnormalities in Mindset’s double transgenic (APP/PS1) mouse model, for example, show a remarkable similarity to the “working memory” deficits typically observed in human Alzheimer’s disease. The APP/PS1 model created by Dr. Karen Duff and other leading neuroscientists is unique in other ways too, especially for its rapidity of amyloid plaque deposition and its highly reproducible and robust phenotype which includes abnormal neuronal growth, reorganization of cholinergic terminals, and the presence of hyperphosphorylated tau, an intermediate in tangle formation which is a prominent feature in Alzheimer’s disease pathology.

The blood-brain barrier is a normal highly specialized anatomical feature that protects the brain from toxins that may be present in blood. Selecting drug compounds that are readily capable of traversing the barrier is a major challenge for the pharmaceutical industry. Equally challenging, is the need to identify and select drugs that are naturally excluded from the brain when the intended therapeutic target is a peripheral organ, such as the heart or liver.

BrainSelect™ is a computational tool to accurately predict whether drugs will penetrate efficiently into the brain and to suggest ways to design new drugs with known permeability properties for the blood-brain-barrier. This software tool will help to screen and create new drug molecules to be effective in the central nervous system.

BrainSelect™ is supported by a unique new database developed in collaboration with leading academic and industrial partners: King’s College London University representing the Blood-Brain Barrier consortium incorporating industrial partners AstraZeneca, Aventis, Eli Lilly, GlaxoSmithKline and Mindset.

A second core component of BrainSelect™ is a blood-brain barrier specific algorithm and proprietary software that permits rapid screening of tens of thousands of molecules based on their molecular structure. Mindset has an agreement with Sirius Analytical PLC  to develop a special version of their ABSOLV program using Mindset’s proprietary database of brain permeation measurements.

Using a powerful combination of protein separation (two-dimensional gel electrophoresis); protein identification (peptide mass fingerprinting and mass spectroscopy); protein characterization (amino acid sequencing and electroblotting) and bioinformatics (cross reference of protein informatics with genomic databases); proteomics enables correlations between the range of proteins produced by a cell or tissue and the initiation and progression of disease.  Proteins that are associated with disease are identified by means of their altered levels of expression between normal and disease states.

Mindset has joined forces with Proteome Sciences PLC  with the support of the BRITECH foundation to discover new protein targets for therapy and diagnostic markers for Alzheimer’s disease. This joint venture benefits from the leadership of Proteome Sciences in proteomic technology and the expertise of Mindset in Alzheimer’s disease. Proteome Sciences uses its high sensitivity proteomic analysis tools to map and quantify changes in protein expression levels using Mindset’s state of the art transgenic mice models of Alzheimer’s disease.