Lightbulb moments

Existing marketed therapies for Alzheimer’s disease target symptoms in the late stages, but don’t arrest progression. With Alzheimer’s disease increasing rapidly in frequency there is an urgent need to discover new drugs that treat affected patients. However, all recent attempts to develop an effective treatment for Alzheimer’s disease have failed, and there is a growing lack of confidence in the efficacy of combating the well-established targets amyloid or tau, leading to the need for a new approach.

Neuro-Bio has discovered the T14 pathway that appears to be the root cause of degeneration and can be monitored in blood as a potential biomarker of disease progression and treatment response. T14 is a 14 amino acid peptide derived from the C terminus of acetylcholine esterase that drives the secondary production of amyloid and tau, induces cognitive impairment in rats and can be intercepted pharmaceutically to stabilize any further cell loss.

T14 is distributed throughout the primarily vulnerable cells, is doubled in the post-mortem Alzheimer mid-brain and is increased significantly in Alzheimer CSF. T14 acts through binding to a modulatory site on the alpha-7 receptor where it enhances calcium entry, thereby inducing excitotoxicity and further proliferation of the receptor itself, thus perpetuating a feedforward cycle of neurodegeneration.

Neuro-Bio has been granted a patent on a novel manner of inhibiting the binding of T14, by means of a cyclized peptide, which has prompted the discovery of linear short peptide inhibitors, now also filed. The company is developing potential therapeutic drugs using the linear peptide variants as templates to design small molecules that will be able to cross the blood brain barrier, for the first time stabilize cell loss and hence eventually treat this debilitating disease effectively. If this treatment were given at the presymptomatic stage, when the T14 blood test revealed neurodegeneration was already underway, then the symptoms may never appear leading to an effective cure for the disease.

Alzheimer heads


  • Is based on 40 years of research into novel brain mechanisms that challenges accepted dogma.
  • Addresses the question of why only certain cells are primarily vulnerable in AD.
  • Pioneers a novel theory of the AD neurodegenerative process that for the first time accounts for all the known clinical facts.
  • Identifies the key pivotal, toxic molecule underlying this pathological process
  • Demonstrates that this toxin is a feature of the AD brain.
  • Is developing a possible blood test whereby this toxic molecule could act as a biomarker.
  • Identifies the molecular target (receptor) of the toxin.
  • Is designing a blocker of the toxin action at this receptor that could lead to an effective therapeutic drug.



For over 40 years it has been accepted that acetylcholinesterase (AChE) is present in a widespread range of neurons and non-neuronal cells without its normal substrate acetylcholine (ACh) and the synthesising enzyme choline acetyltransferase (ChAT) Could it have an additional, non-enzymatic function? This was our starting point.

Although not a requirement for its familiar role in cholinergic transmission, AChE is released into CSF, detectable locally from brain areas linked to neurodegeneration such as the substantia nigra, where its secretion can be visualised in real-time and monitored on-line in the freely moving animal.

As a signalling molecule independent of cholinergic transmission, ie where its primary site can be irreversibly blocked with Soman, AChE has electrophysiological, biochemical/pharmacological, and behavioural actions which in all the studies cited above cannot be replicated by another enzyme (butyrycholinesterase) which will nonetheless also hydrolyse ACh.

This novel, non-enzymatic function of AChE is to promote cell growth: it has a non-cholinergic trophic action in organotypic cell cultures of rat midbrain, via activation of calcium influx.

However in higher doses, or for a protracted period of administration, the trophic action of AChE can turn toxic.

Since (a) AChE is present in all the cell populations primarily vulnerable in neurodegeneration, irrespective of the diverse transmitter systems and (b) calcium influx can switch from trophic to toxic effects dependent on age, then (c) neurodegeneration could be a region-selective, aberrant form of development, with ‘non-cholinergic AChE as the pivotal signalling molecule.

The crucial part of the AChE molecule has been identified as a 14mer peptide, ‘T14’ at the C-terminus with homology to amyloid-beta which as an independent agent enhances calcium currents, which in turn can have a trophic-toxic, ‘excitotoxic’ action.

The action of T14 is modulatory, ie enhancing calcium influx via an allosteric site on the alpha-7 receptor which leads to the secondary generation of amyloid and hyperphosphorylation of tau.

Sustained application of the T14 leads to further upregulation of the alpha-7 receptor. Hence the peptide is enhancing availability of its own target, and providing a feed-forward mechanism to continue the degenerative process.

The significance of T14 in neurodegeneration has now been proven directly as it is elevated in the brains and CSF of Alzheimer patients to levels corresponding to those seen in development.

The action of T14 in triggering an inappropriate recapitulation of development, via the alpha 7 receptor, also occurs in metastatic cancer cells, suggesting a general and basic underlying biological mechanism for cell signalling throughout the body that has as yet been undiscovered.