Use of the structure of serum amyloid P, a modulator of amyloid formation

The UCL spinout company Pentraxin Therapeutics Ltd designed and developed potential treatments for Alzheimer's disease and amyloidosis. These treatments are based on the structure of serum amyloid P, which was first determined by a team led by Professor Steve Wood (UCL Biosciences).

Amyloidosis is a group of rare but serious diseases caused by deposition of abnormal protein fibres, amyloid, in tissues and organs throughout the body. The proteins making up amyloid fibres are abnormally folded and cannot be cleared away, causing them to build up in tissues and organs, leading to organ failure. A particular type of amyloid protein also occurs in the brain of people with Alzheimer's disease.

The most wonderful news about amyloidosis we had heard in the past eight years. - Amyloidosis Australia

Amyloid fibres formed from different proteins have essentially the same structure. A number of other proteins have been discovered to be associated with amyloid fibres, among them a protein called serum amyloid P (SAP). SAP contributes to the formation and persistence of amyloid deposits. Knowledge of the three-dimensional structure of this protein has been an essential pre-requisite to understanding the mechanism of its interaction with amyloid. The structure of SAP was first determined by a group led by Professor Steve Wood at Birkbeck, who has continued his productive work on amyloid proteins after leaving Birkbeck, first at Southampton and then at the UCL Centre for Amyloidosis and Acute Phase Proteins. Building on Professor Wood's research, a compound, CPHPC, was developed by Sir Mark Pepys (UCL Division of Medicine) for therapeutic application. CPHPC helps to clear SAP from the blood and significantly stabilises some patients with systemic amyloidosis. In 2001, Pentraxin Therapeutics Ltd (PTL), was spun out of UCL to develop treatments for systemic amyloidosis and amyloid-related diseases; SAP became its first focus, resulting in a series of patents.

The PTL team has now licensed a combination of CPHPC and anti-SAP antibodies to GlaxoSmithKline (GSK) as a treatment for systemic amyloidosis. The first Phase I clinical trial of the combination therapy began recruiting patients diagnosed with systemic amyloidosis in 2013. GSK have hailed the importance of their collaboration with the UCL Centre for Amyloidosis and Acute Phase Proteins as part of their strategy of academic engagement in drug discovery. The potential value of this combination therapy has already attracted the attention of patient groups, despite its early stage of development.