Novel treatments for Alzheimer’s disease (AD) using stable analogues of GIP (U140A)

Tuesday, 25 October 2016

Ulster researchers within Ulster’s Biomedical Sciences Research Institute, has recently carried out proof of concept studies aimed at advancing a potential new class of molecules for treatment of neurodegenerative disease.

Problem Being Solved

·       Alzheimer’s disease (AD) is a chronic, degenerative disease of the brain for which there are currently no drugs available for its prevention or cure.  Recent estimates suggest there are currently 44 million people worldwide affected by the disease with one new case being diagnosed every 3.2 seconds. 

·       A recent study published in the medical journal of the American Academy of Neurology has pinned AD as the 3rd leading cause of death in the U.S. and the global cost of the disease is estimated to be 1% of the world’s GDP ($605 billion).

·       The incidence of AD and other forms of dementia is expected to continue to grow significantly with an estimated 100 million people impacted worldwide by 2050.  As such, there is a clear need for the development of disease modifying drugs capable of prevention, delay of onset, slowing of progression or improving the symptoms of this devastating disease.

Technology

Building upon preliminary studies focused on a proprietary approach that employs a series of promising GIP analogues, Ulster researchers have recently shown Ulster’s lead GIP analogue NAcGIP(Lys37PAL) to significantly reduce beta amyloid and dense core plaque load in a transgenic mouse model of Alzheimer’s Disease (APP/PS1). In addition, Ulster’s lead compound has been shown to partially restore neurogenesis, preserve synaptic density and improve recognition memory.

Benefits/Applications

 

·       Proof of Concept studies have shown that NAcGIP(Lys37PAL) has clear effects in improving symptoms in a transgenic mouse model (APP/PS1) of Alzheimer’s Disease. 

 

o   NAcGIP(Lys37PAL) reduced beta amyloid plaque load by 27% and dense core congophilic plaques by 45%, a marker closely associated with neuronal cell loss and advanced disease pathology.

 

o   NAcGIP(Lys37PAL) significantly increased neurogenesis by 46%, suggesting the peptide has ability to stimulate the formation of new neurons.

 

o   NAcGIP(Lys37PAL)-treatment resulted in a 78% reduction in aggregated beta amyloid oligomer levels compared with APP/PS1 saline-treated mice, which was greater than the reduction observed in liraglutide-treated mice.  Such data suggests the peptide has the ability to improve neuronal communication in vivo.

 

·       NAcGIP(Lys37PAL) is a stable synthetic analogue of GIP with a low likelihood of immunogenic response due to high degree of structural similarity to native peptide.

 

·       Previous in vivo studies have shown NAcGIP(Lys37PAL) does not adversely affect blood glucose levels of non-diabetic mice.

 

·       GIP receptors are highly expressed in the hippocampus and GIP analogues (such as NAcGIP(Lys37PAL)) may therefore have greater effects on learning and memory as compared to GLP-1 agonists.

 

·       Ulster holds rights to a strong IP portfolio comprising granted claims on composition of matter and use of lead compounds for treatment of AD.  Exclusive access to Ulster’s portfolio would provide an opportunity to enhance a partner’s positioning in the fast growing space of incretin hormone analogues for treatments of the CNS.

 

Opportunity/Partnership Sought

 Ulster University is looking for a potential partner or collaborator to progress this technology. An exclusive licensing of Ulster’s U140A technology provides an opportunity to enhance a licensor’s existing intellectual property pipeline or competitive positioning of this emerging technology.

In addition, inventors of this technology are able to provide valuable know-how in order to assist in its successful commercialisation.

 For more information please contact:

 Dr Oonagh Lynch

Technology Commercialisation Executive

Research & Impact

Tel: +44 (0) 28 9036 6707

Mob: +44 (0) 77 6536 3191

Email:ot.lynch@ulster.ac.uk