A series of reagents that promise potential for early diagnosis of Alzheimer's Disease using MRI

The reagents comprise gadolinium, a short, proprietary amyloid binding domain and a BBB penetrtion sequence

Background:

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder that leads to cognitive, memory and behavioural impairments.  Accounting for nearly 70% of all dementia cases, it is the leading cause of dementia.  As the population ages, the number of people suffering from dementia worldwide is predicted to rise to 81.1 million by 2040. 

The origin and development of AD is complex and involves many molecular, cellular and physiological pathologies.  The main histological features of AD are (i) extracellular  β-amyloid (Aβ) plaques (or senile plaques), (ii) cytoplasmic neurofibrillary tangles (NFTs), and (iii) loss of neurons and synapses in certain regions of the brain.

Clinical setting

Definitive diagnosis of AD in living patients has been a goal since the first description of the disease in 1906.  While experienced neurologists can diagnose AD with an accuracy approaching 90%, an examination of the post-mortem brain is still required for substantiation.  The ability to separate early AD from other causes of dementia is extremely important in that clinical management decisions and prognosis depend upon the correct diagnosis.

The Technology

The group at St George's has synthesised a unique β-amyloid binding peptide based on a recognition sequence of a relatively small number of amino acids.  This peptide, when complexed with gadolinium and a moiety enabling passage across the blood brain barrier, has exhibited efficacy in imaging of early β-amyloid aggregates by MRI in vivo. This reagent would enable definitive diagnosis of suspected AD before presentation with symptoms, allowing maximal preventative treatment, and quantitative monitoring of progression. 

Due to the small size of the binding moiety, the reagent is less toxic than other amyloid binding compounds generated, for example amyloid 1-40.  It has been shown in vitro to have low toxicity against neuronal cells and high binding affinity.  The unique peptide configuration of the reagent gives rise to enhanced resistance to proteolytic degradation and turnover in brain tissue, therefore promoting efficacious diagnosis at minimal reagent toxicity.  As well as the superior resolution offered by MRI compared to PET imaging, MRI is cheaper to set up and run than PET and is much more widely available at present.

The group are currently planning work to optimise the regent for amyloid binding and entry into the brain.  The optimised reagent(s) will then be validated.

Early Stage

UK patent application claiming the sequence of the amyloid binding moiety was filed on 5th May 2006.

 St George's are offering this technology as a licensing or collaboration opportunity.