The UCL Centre for Amyloidosis and Acute Phase Proteins has designed and
developed new chemical entities targeting serum amyloid P component (SAP),
C-reactive protein (CRP) and transthyretin, for novel therapeutic
approaches to amyloidosis, Alzheimer's disease, cardiovascular and
inflammatory diseases. The UCL spin out company, Pentraxin Therapeutics
Ltd, founded by Sir Mark Pepys to hold his intellectual property (IP), has
licensed two programmes to GlaxoSmithKline (GSK). These highly
synergistic, collaborative multi-million pound developments, strikingly
exemplify new working relationships between academia and the
Measurement of hormones is essential to the understanding and diagnosis
of endocrine diseases. White and her research group have developed unique
antibodies that are widely used in diagnostic assays for
adrenocorticotrophic hormone (ACTH) and related peptides, including the
first and only kit for measuring pro-opiomelanocortin (POMC), the
precursor of ACTH. These assays are used worldwide for diagnosis,
decisions on treatment, monitoring for recurrence of tumours and prognosis
in a number of patient groups with life-threatening endocrine disorders.
Global sales of the ACTH Elecsys tests by Roche exceeded 6 million kits
since 2008. AstraZeneca has used the POMC and ACTH assays in its drug
discovery programmes in the cardiovascular and metabolic diseases therapy
area. The antibodies therefore have had health impact in relieving
suffering and in improving patient care, as well as commercial impact in
worldwide sales of assays and influencing drug development strategies.
Research by Dr Andrew Martin at the UCL Research Department of Structural
& Molecular Biology
has led to a series of antibody-related tools being made available for
free use over the Web. One
of these, Abysis, has been visited over 360,000 times by over 8,000 users.
Abysis has also been
released under a commercial license and has been purchased by companies
ranging from small
biotechs to large pharma for use in their antibody therapeutic development
pipelines, allowing them
to identify unusual features of their sequences and to improve strategies
for humanisation. Martin
has also acted as an expert witness for drug companies in patent disputes.
Researchers in the University of Cambridge's Department of Zoology have
developed a new
methodology to analyse pathogen evolution. This `antigenic cartography'
has led to the group
becoming integrally involved in the World Health Organisation (WHO)
influenza vaccine strain
selection process, and has directly contributed to more accurate and
appropriate flu vaccine
design, with associated international impacts on disease prevention and
public health (the flu
vaccine is given to ~350 million people annually). The research has
directly affected how public
health professionals conduct disease surveillance and sampling.
Since its discovery in the 1980s, avian metapneumovirus (AMPV) has spread
in poultry populations worldwide with major adverse health and food
security implications for commercial chickens and turkeys. Research at the
University of Liverpool (UoL) led to the registration of a live vaccine in
1994 which has played a global role in AMPV control, thereby safeguarding
the supply of poultry meat and eggs. Recent research and development at
the UoL has identified key control measures, relating to vaccine
application, vaccine selection, efficacy and safety, which have had a
significant impact on poultry health and consequently, poultry producers
and consumers. In particular, demonstration that live AMPV vaccines can
revert to virulence, that vaccine type applied influences field protection
and that continuous use of a single vaccine can influence circulating
field strains, has resulted in UoL leading policy making with regard to
current AMPV vaccine protocols.
Research at UCL pioneered B cell depletion to treat rheumatoid arthritis
(RA) and also stimulated the development of B-cell-directed therapies for
other autoimmune rheumatic, haematological and neurological diseases. Now
NICE approved, B cell depletion (based on rituximab) in RA is as effective
as the alternative (anti-TNFα drugs) and an option for patients unable to
gain benefit from anti-TNFα drugs. Rituximab offers drug-cost savings of
up to £5,000/annum/patient and for many is a more convenient therapy,
being given as an infusion only every five months apart, or more. B cell
depletion has also proved to have an excellent safety profile, with many
receiving repeated courses of treatment. As a consequence of UCL research,
rituximab has brought substantial benefit to patients with many autoimmune
diseases, including over 200,000 who have been treated with rituximab for
RA so far.
Research investigating genetic and environmental interactions leading to
skin barrier breakdown in atopic eczema has delivered health benefits by
improving the prevention and treatment of this condition. We found that
established emollient formulations (e.g. Aqueous Cream BP) containing the
harsh emulsifier sodium lauryl sulphate (SLS) damage the skin barrier in
patients with atopic eczema and identified an underlying molecular
mechanism. Consequently, the NICE Quality Standard and Guidelines now
reflect our advice that Aqueous Cream should not be used as a leave-on
emollient, SLS has been removed from all emollient formulations in the UK
and we have helped develop the next generation of `SLS-free' skin-care
products. Medicines regulators including the Medicines and Healthcare
products Regulatory Agency (MHRA) and New Zealand MedSafe have also issued
new advice as a result of our research.
UCL spin-out company BioVex was launched in 1999 to exploit research
undertaken by David Latchman at the UCL Medical Molecular Biology Unit,
Department of Biochemistry. (This department is now part of the Department
of Structural and Molecular Biology, UCL/Birkbeck and Latchman is now
Master of Birkbeck.) Biovex worked to develop inactivated herpes simplex
viruses as therapies, and a promising dual-action oncolytic vaccine for
solid tumours, OncoVEXGM-CSF, was taken into successful Phase
II trials. In 2011 the company was bought out by Amgen for $1 billion —
still the largest ever cash sale of a UK biotech — and Amgen has now taken
this virus into a Phase III trial with promising initial results.
Impact: Animal Health and Welfare, Economics: The BVD vaccine
associated with emergence of BNP was withdrawn from sale.
Significance: BNP cases have been reported worldwide. On affected
farms, the case fatality rate is very high, with losses of up to 5% of
calves in a herd being reported. Despite the vaccine being withdrawn,
cases continue to be found in some calves born to dams that have been
historically vaccinated. In addition, reporting has increased due to
increased awareness and Zoetis subsidising post-mortem examinations.
However, as an indirect measure, the number of cases being diagnosed at
post-mortem at SRUC fell by 42% between 2012 and 2013.
Beneficiaries: Livestock Industry, Animal Health Company, Farmers.
Attribution: Work performed by University of Edinburgh (Penny,
Morrison, Sargison, Bell) and SRUC (Hosie, Howie, Kerr, Caldow) identified
BNP as a new disease entity, elucidated the cause, and developed
strategies to reduce the incidence. This also involved a collaboration
with the Moredun Research Institute (Willoughby)
Reach: BNP is recognised world-wide (a peak of 4500 cases in 2011)
including France, Germany, United Kingdom, Ireland, Netherlands, Belgium,
Luxembourg, Italy, and Spain. The disease is unknown in countries which do
not vaccinate against BVD (Denmark, Austria, and Switzerland)
Invasive pulmonary aspergillosis (IPA) is a frequently fatal disease of
haematological malignancy patients, caused by fungi from the genus Aspergillus.
Dr Christopher Thornton has developed and commercialised a novel
point-of-care test for the diagnosis of IPA with an Aspergillus-specific
monoclonal antibody (mAb) JF5 generated using hybridoma technology. Using
this mAb, he has developed a lateral-flow device (LFD) for the rapid
detection of Aspergillus antigen in human serum and
bronchoalveolar lavage fluids (BALf) that signifies active infection.
Commercial exploitation of the patented technology has been met through
the establishment of a University of Exeter spin-out company, Isca