Introduction
The first direct renin inhibitor has recently been licensed for use
as an anti-hypertensive drug in
both the United States and Europe. Many analysts suggest that
Aliskiren (Tekturna, Rasilez)
(Novartis), as the first of its class to market, has blockbuster
potential, with projected annual
sales of > $2.5 billion by 2012. The market for blockers of the
renin angiotensin system (RAS) is
large - in excess of 70% of those over 50 years of age suffer from
hypertension, diabetes
mellitus, coronary artery disease, renal dysfunction or stroke. Use
of the REN -5312C/T genotype
as a pharmacogenetic assay offers a significant opportunity for the
marketing of renin inhibitors.
This common polymorphism in a renin distal enhancer element,
REN-5312C/T, identifies a large
target population (65% of the total population) who respond better
to renin inhibition than to
other blockers of the RAS. Hence this assay has the potential to
increase market penetrance of
Aliskiren and other renin inhibitors as first line therapy in many
millions of patients.
Technology
REN-5312C/T
had been reported to influence in
vitro gene
transcription in transfected human
choriodecidual cells. Researchers at RCSI have provided the first
evidence that REN–5312C/T has
in
vivo functional
activity. Carriage of the -5312T allele, a specific marker for a single
renin
haplotype, is associated with both elevated ambulatory and elevated
clinic blood pressure (BP)
levels in healthy humans. Of greater importance was the discovery,
by the RCSI team, that the
polymorphism predicts BP lowering responses to RAS blockade in
hypertensive patients, and
that this prediction is additional to, and independent of plasma
renin activity. Clinic and
ambulatory pressure responses to aliskiren among REN-5312CC
homozgotes were almost
double those achieved among T allele carriers. By contrast BP
lowering responses with losartan
was greatest among REN-5312T allele carriers.
Moore N, Dicker P, O’Brien J, Stojanovic M, Conroy R, Treumann A,
O’Brien E, Fitzgerald D, Shields D,
Stanton AV. Renin gene polymorphisms and haplotypes, blood pressure
and responses to renin angiotensin
system inhibition. Hypertension
2007.
RCSI Page 2
Applications
Personalised medicine – Selection of the optimal blocker of the RAS
in individual hypertensive
patients.
Advantages
If genotyping the REN-5312C/T polymorphism is confirmed to identify
individuals who get 50-
80% greater BP lowering with particular classes of therapy; the
current physician “trial and
error” approach to matching a drug with a particular patient could
be superseded. Improved
control of BP could be achieved, with the same or a lesser number
of prescription drugs. Control
of BP is likely to be achieved more rapidly with a reduced number
of clinic visits. Patients would
be less likely to be prescribed drugs that would not yield a
beneficial response, and therefore
would not be exposed to adverse drug reactions unnecessarily.
Ultimately protection from
atherosclerotic vascular events could be greatly
enhanced.
Patent
status:
WO 2006/082570
This opportunity is available for licensing with a number of
potential commercial partners
namely (1) Genotyping companies (for physician end use) (2)
pharmaceutical companies (for
clinical development and physician end use), and (3) medical device
companies (point of care
assays).
Contacts:
Dr. Gearóid Tuohy, RCSI Technology Transfer, 123 St Stephen’s
Green, Dublin 2, Ireland.
Email: gearoidtuohy@rcsi.ie Tel: +353 1 4022362
Dr Aoife Gallagher, RCSI Technology Transfer, 123 St Stephen’s
Green, Dublin 2, Ireland.
Email: aoifegallagher1@rcsi.ie. Tel: +353 1
4022394
Dr Liz Moran, Enterprise Ireland, East Point Business Park, Dublin
3.
Email: liz.moran@enterprise-ireland.com. Tel: +353 1
7272696
Principle Investigator:
Prof. Alice Stanton, Dept. Molecular & Cellular Therapeutics,
Royal College of Surgeons, 123 St Stephen’s
Green, Dublin 2, Ireland. Email: astanton@rcsi.ie. Tel: +353 1
40222796