Alzheimer's Disease Breakthroughs
Scientists at the Tanz Centre have contributed to several fundamental breakthroughs in our understanding of Alzheimer’s disease (AD), including:
- The discovery of several key components of the γ-secretase enzyme, which performs the final step in the production of the neurotoxic amyloid β-peptide (A).
Knowledge of this enzyme complex has turned out to have major scientific interest because: (i) it is involved in many important normal processes necessary for life; and (ii) because its activity in producing neurotoxic (A) can be blocked by drugs, which could be useful to prevent or treat Alzheimer’s disease (2000, 2006).
- The demonstration that although the presenilin protein (PS1 and PS2) components of γ-secretase complexes have similar amino acid sequences, they have very different biochemical properties and different functions. This is turning out to be important for the development of drugs which selectively inhibit the role of these proteins in the generation of neurotoxic Aβ by the γ-scretase enzyme (2006).
- The development of a robust mouse model of AD, which develops amyloid plaques, cognitive and memory impairment, synaptic loss, and accelerated mortality. This mouse is now being used by numerous academic and industrial researchers to investigate the mechanisms of nerve cell injury and the effects of potential new therapies (2000).
- The discovery that antibodies to A can block cognitive decline in mouse models of AD, and the discovery of the precise part of A that these antibodies must bind to in order to block AD. These two discoveries encouraged the use of immune (active or passive vaccine-based) therapies for AD in humans, and the refinement of these immune therapies to avoid induction of allergic encephalitis (an occasional complication of vaccination with the full-length A-peptide) (2000, 2002).
- The discovery that scyllo-inositol (AZD103) can:
i) inhibit the accumulation of A into small neurotoxic aggregates (termed “oligomers”); and
ii) block many of the features of AD in mouse models of this disease.
These two observations led to the initiation of human clinical trials of scyllo-inositol in patients with AD (2006).