Researchers at the Dunn School of Pathology at the University of Oxford
have played a major role in the development of an effective and innovative
treatment for the chronic debilitating disease multiple sclerosis (MS).
Research arising from the work of immunologists in Oxford, and partner
neuroscientists in Cambridge University, has shown that low dose treatment
with the lymphocyte depleting antibody alemtuzumab can break the cycle of
disease in MS. Alemtuzumab acts by re-setting the immune system, leading
to long-term arrest or remission, without increasing the risk of infection
or malignancy. Large-scale studies since 2008 have shown that treatment is
more effective and better tolerated than conventional forms of therapy. In
June 2013, the European Medicines Agency's Committee for Medicinal
Products for Human Use recommended that the drug be licensed for people
with active relapsing-remitting MS. The research by Oxford University and
its collaborators into the use of alemtuzumab in MS has been shown to
benefit patients; it offers hope to millions of sufferers worldwide; and
has had a major impact on the pharmaceutical industry.
Psoriatic arthritis (PsA) is a chronic inflammatory disease of joints,
skin and tendons that affects 0.5-0.8% of the population worldwide. PsA
can cause substantial psychological and social problems and also causes
increased risk of death from cardiovascular disease. Research conducted by
Prof Iain McInnes at the University of Glasgow in partnership with leading
pharmaceutical company, Janssen, has provided robust evidence of the
clinical benefits and safety of the cytokine blocker ustekinumab, leading
to its approval for use for PsA by the European Medicines Agency in July
2013. This was the first approval of a PsA drug with a new mode of action
in a decade, providing a novel treatment for approximately 1.25 million
PsA patients across Europe.
Alemtuzumab, a humanised therapeutic antibody, is a major addition to the
immunosuppressive agents used for organ and stem cell transplants.
Administered as an induction
agent in a short course of treatment, alemtuzumab reduces the incidence of
graft rejection without
preventing recovery of the patient's ability to fight infection.
Alemtuzumab also decreases graft
versus host disease, a vital factor in the treatment of aplastic anaemia
and acute leukaemias.
Furthermore, its important role in minimising immunosuppressive therapy
helps prevent treatment-associated
problems for the patient. Currently used off-licence for transplants,
improves patient survival and healthcare.
Sustained research by the University of Oxford's Mahidol Oxford Tropical
Medicine Research Unit in Thailand (MORU) has been the driving force
behind the current World Health Organization recommendations for the
management of acute and chronic infection in patients with melioidosis.
This research has motivated improvements in treatments and provided new
strategies to identify at-risk populations, enabling clinicians to make
early diagnoses. Melioidosis is a major cause of severe illness in parts
of Southeast Asia and there are increasing numbers of cases in India,
China, and Brazil.
Multiple Sclerosis (MS) is the most common disabling neurological disease
of young adults in the UK, affecting 1 in 800 of the population. In most
patients the early years are characterised by relapse and remissions;
relapses are often disabling and permanent disability occurs when
remissions fail to recover fully. Research at the UCL Institute of
Neurology — from early MRI studies through phase 1-3 clinical trials — has
resulted in the licensing of natalizumab for highly active relapsing
remitting MS. Natalizumab is now widely used to treat such patients with
very good efficacy and close monitoring. Natalizumab is a potent treatment
that has reduced relapse rate by two-thirds and relapse-related disability
by 50%. By July 2013, over 115,000 patients around the world had received
Jayne's team have co-ordinated a sequence of randomised clinical trials,
that have defined the standard of care for ANCA vasculitis treatment and
shaped national and international guideline statements, NHS national
commissioning guidance and an on-going NICE assessment. Together with Ken
Smith his group have pioneered the use of the B cell-depleting agent
rituximab, in vasculitis, contributing key evidence that led to its
licence approval (USA and EU) for this indication. Ken Smith's group
supported by Jayne's clinical team have discovered novel therapeutic
biomarkers, patented and being assessed in Phase II clinical studies, that
promise to deliver "personalised medicine" in this and related conditions.
These activities have harmonised the management of vasculitis, are
improving patient outcomes, and have provided a resource for on-going
scientific and clinical studies.
Professor Platt and colleagues at the University of Oxford have developed
the drug miglustat, the first oral therapy for rare lysosomal storage
diseases. These are primarily neurodegenerative diseases that affect 1 in
5,000 live births, always leading to premature death. In 2009, miglustat
became the first treatment to be licensed for treating neurological
manifestations in Niemann-Pick disease type C (NPC). It is now prescribed
for the majority of NPC patients worldwide, and has led to significant
improvements in both life expectancy and quality of life. Miglustat was
approved for type 1 Gaucher disease in 2002 and, since 2008, has proved an
effective treatment for patients previously stabilised with enzyme
replacement therapy; miglustat has the additional benefit of improving
bone disease. Sales of miglustat since 2008 have generated CHF 315 million
in revenues for Actelion, the company sublicensed to sell the drug.
Research led by University of Oxford scientists has resulted in
widespread use of the humanised therapeutic antibody, Campath
(alemtuzumab), in patients with chronic lymphocytic leukaemia (CLL).
Licensed by both the European and American regulatory authorities in 2004
for the treatment of CLL, Campath is used as first-line treatment for
patients with aggressive forms of the disease and following relapse. It
can induce long-term clinical remission even in cases resistant to other
drugs. Campath has now been used in approximately 15,000 patients, and has
generated revenues of approximately £750 million from the licensed
treatment of CLL.
In 2012, around 19,500 kidney transplant operations were performed in the
UK and USA. The greatest infection risk to transplant recipients is from
cytomegalovirus (CMV), the standard 2-4 week treatment for which involves
an average of 5 days as an inpatient, which can cost up to £13,000.
University of Glasgow research has led to revised standards of care for
the prevention and treatment of CMV disease in kidney transplant
recipients (KTRs). First, that antiviral treatment with oral
valganciclovir for 200 days can be used to prevent CMV disease in
postoperative KTRs and is twice as effective as treatment for 100 days.
Secondly, the team found that the use of oral valganciclovir was a
practical and cost-effective alternative to intravenous ganciclovir for
treatment of mild CMV disease in solid-organ transplant recipients. Since
2009, the use of these therapies has been recommended in key national and
international guidelines for the care of KTRs. The research also provided
the evidence base that was used for evaluating, and subsequently amending,
the marketing authorisation of oral valganciclovir for use in preventative
treatment of CMV disease in KTRs in the UK and USA.
Research conducted by Professor TM Cox has led to several advances in the
management of lysosomal storage disorders; i) development of miglustat
(Zavesca®); now available throughout the world (EMA and FDA approved) for
adult patients with Gaucher's disease and throughout the European Union
and five other countries worldwide for adult and pediatric patients with
Niemann- Pick type C disease, ii) development of the potential successor
eliglustat; now in Phase 3 clinical trials, iii) identification of a
biomarker for Gaucher's: CCL18/PARC, now incorporated into NHS standard
operating procedures for monitoring therapeutic intervention. His
pre-clinical research into gene therapy for Tay-Sachs disease also helped
establish the NIH-funded Gene Therapy Consortium and gain the FDA's
pre-IND approval for clinical trials in 2013, which together have raised
public awareness of this disease.