An alternative to liver transplantation

LONDON—The University of Cambridgehas announced a landmark partnership with pharmaceutical giant GlaxoSmithKlinePLC (GSK) in an effort to combat Alpha-1 antitrypsin (A1AT) deficiency, aprevalent genetic disorder in the United Kingdom. The partnership centers onthe recent work of a team led by Cambridge professor Dr. David Lomas at theUniversity's Cambridge Institute for Medical Research (CIMR), which hasidentified a molecular mechanism that plays a major role in the disorder'sdevelopment into a life-threatening liver disease in many patients.

Under the terms of the agreement,the university and Cambridge Enterprise, the school's commercialization group,will receive an undisclosed upfront payment, as well as success-based financialsupport from GSK linked to reaching preset milestones, plus royalties on salesof any products resulting from the collaboration.

A1AT deficiency is one of the mostcommon genetic disorders in the UK. An estimated 1 in 2,000 Britons is affectedby a deficiency in the A1AT protein, which is produced in the liver andcirculates to the lungs. The protein normally protects the lungs from enzymesthat can cause lung tissue to break down over time, but the protein does notcirculate properly in patients who inherit the A1AT deficiency. Instead, themutant protein accumulates in the liver cells, leading to cirrhosis and otherliver ailments, while the lungs go unprotected and become predisposed tobreaking down, often leading to early-onset emphysema.

Lomas has been researchingantitrypsin deficiency for more than 20 years, and has earned a reputation as amajor contributor in the field. This collaboration will build upon Lomas andhis team's expertise and knowledge base. GSK will be responsible foridentifying lead compounds, the medicinal chemistry and the clinical studies.Cambridge will be responsible for assessing the lead compounds in biologicalassays.

This is not the first time thesetwo groups have worked together. An earlier collaboration between Cambridge andGSK generated promising preliminary data that both parties were eager to buildupon and further explore through this newest venture.

"Three years ago, GSK began aresearch collaboration with (Cambridge) in the belief that combining our deepunderstanding of the disease with GSK's drug discovery expertise wouldsignificantly increase the chances of finding effective new treatments," saysLomas.

The partnership aims to developnew therapeutics that would radically improve the prognosis for patientsdiagnosed with A1AT deficiency.

"The only current treatment forliver disease associated with antitrypsin deficiency is liver transplantation,"says Lomas. "We hope to develop a small molecule that prevents the accumulationof mutant antitrypsin within liver cells, increases secretion and so removesthe requirement for transplantation."

The commercial opportunities for asmall-molecule therapy as an attractive alternative to transplantation in afairly prevalent disorder are readily apparent.

"We are delighted to be involvedwith GlaxoSmithKline's Discovery Partnerships with Academia (DPAc) alliancewith the goal of developing and commercializing medicines to treat a clearunmet medical need," said Dr. Emma Barker of Cambridge Enterprise in a pressrelease announcing the partnership.

The DPAc program is an ongoingeffort on the part of GSK to partner with academic institutions to translateinnovative research into medicines that benefit patients by working towardshared goals and by sharing information.

"This (collaboration) will see GSKand Cambridge scientists work together to build on the work of Cambridgeresearchers," says Eleanor Bunch, media manager at GSK. "It is hoped thatcombining this long-term research with GSK's expertise in drug discovery willfacilitate the development of new treatments for this disease."

Lomas' research is funded by theMedical Research Council, a publicly funded organization in the United Kingdomdedicated to improving human health.