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Issue 01 - june 2013
BERENICE is an acronym for: “Benznidazol and Triazol REsearch group for Nanomedicine and Innovation on
Chagas diseasE”.
BERENICE is a Collaborative Project which is funded under the European Community’s 7th Framework Programme.
Grant agreement number: HEALTH-30593
Contents
• What is BERENICE? ......................... 1
• The European Commission
commitment with neglected
diseases............................................ 1
• News ................................................. 2
• Social burden of Chagas disease. 2
• Promising novel treatments for
chagas disease based on nano
drug delivery systems ..................... 3
• Facing Chagas by the pharma
industry: the need for open
innovation ........................................ 4
The European Commission
commitment with neglected
diseases
BERENICE Project is supported by
the European Commission, under
the 7th Framework Program. The
EC commission uses this instrument
through several calls to promote
and support R&D efforts to develop
and transfer novel technological
achievements to fight neglected
diseases, covering the existing innovation gap.
In this case, the Topic puts special interest in the development of
“Low-cost interventions for disease
control in resource poor settings”,
as it is necessary to give solutions
which are not only good from a
technological point of view but also
feasible to be applied in scarcity of
resources context.
www.berenice-project.eu
What is BERENICE?
B
ERENICE (BEnznidazol and triazol
REsearch group for Nanomedicine
and Innovation on Chagas disease) is a European research network
(Collaborative Project) coordinated
by Vall d’ Hebron University Hospital
and its Research Institute (ICS-HUVH,
Barcelona, Spain). Starting in September
2012, this 5-year project is supported by
the European Commission under the
Health Innovation Work Programme of
the 7th Framework Programme.
The main objective of BERENICE project
is to obtain a more effective, better tolerated and low-cost formulation of a
drug with trypanocidal activity to cure
Chagas disease in endemic and non
endemic countries.
Chagas disease is an important health
problem in Latin America and a challenge in non endemic countries. Its
prevalence is estimated between 8
and 10 million people infected and
approximately 14,000 deaths/year. It
represents the second highest burden
of disease among Tropical Diseases in
the Americas.
Although Chagas disease has been
identified and described for more than
100 years, the therapeutic alternatives
are limited and merits exploration: benznidazole and nifurtimox are the only 2
drugs available for treatment. Both benznidazole and nifurtimox have frequent
side effects, especially in adults, requiring
discontinuation in up to 10% of patients.
The encapsulation of benznidazole
using nanotechnology will generate a
new drug delivery system. A better toxic
profile will be obtained because of
the reduced amount of benznidazole
used, which will consequently lower the
side effects as wells as the cost.
BERENICE brings together 8 European
and Latin American partners: Nanomol
Group of the Materials Science Institute
of Barcelona-Spanish Scientific Research
Council (ICMAB-CSIC), NanoBioCel
Group of the University of Basque
Country (UPV/EHU), Instituto de Higiene e
Medicina Tropica de Lisboa, Parasitology
Laboratory of the Faculty of Pharmacy
at the University of Barcelona, Fundação
Oswaldo Cruz, National Institute of
Parasotology Argentina Dr. Mario Fatala
Chaben, and two pharmaceutical companies, ELEA and PRAXIS.
Berenice Project - Newsletter
1
NEWS
GENERAL ASSEMBLY
On June 26th 2013 the Second
General
Assembly
of
the
BERENICE project will be held in
Barcelona.
This meeting will congregate
all Berenice partners from 3
European Member States (Spain,
France & Portugal) and 2 countries in South America (Argentina
& Brasil), under the coordination
of the Hospital Universitari Vall
Hebron, Barcelona, Spain.
The purpose of the meeting will
be the discussion of the project
progress, especially the work
packages WP2, WP3 and WP4
and the presentation of the
next deliverable scheduled for
August 2013 (month 12 of the
project).
CONGRESS
From 20 to 23 April 2013 took
place in Lisbon the 2nd Tropical
Medicine National Congress
organized by the Institute of
Hygiene and Tropical Medicine
(IHMT). A round table in Chagas
disease was organized with the
participation of the Coordinator
and some of the partners.
Within the Congress it also was
held the 3rd working meeting
of Berenice project in which the
consortium had the opportunity
to exchange key information at
at this stage of the project.
Social burden of Chagas disease
hagas disease is a parasitic infection caused by the protozoa
Trypanosoma cruzi which affects
about 10 million people worldwide.
About 80% of infections occur through
the main vector, the kissing bug, which
is generally found in adobe houses. It
also could be transmitted from mother
to child during pregnancy, blood transfusion, organ transplantation, and ingestion of contaminated food.
C
The barrier in the diagnosis
and treatment
Chagas disease is directly linked to the
precarious conditions of life from sufferers and is one of the biggest health
problems in Latin America. Due to immigration, the disease also affects people in the United States and Europe.
Simplified diagnostic tools and better
treatments adapted to different contexts are also needed. These have to
be accessible to patients in their health
centers and close from their community.
In Latin America, the parasite T. cruzi is
transmitted primarily through infected
feces of triatomine bugs (known as kissing bugs) that feed on blood. Usually
they live in cracks and holes of poorly
constructed houses in rural and suburban areas. They remain hidden during
the day and become active at night
feeding on human blood and other
mammals. Generally, they bite into
an exposed area of the skin such as
the face, and defecate near the bite.
The parasites enter into the body when
the person is bitten and push instinctively rubbed feces into the bite, eyes,
mouth, or an open skin lesion.
Not only new drugs are needed to go
along with this process, but also health
authorities must ensure that the necessary drugs are available in all concerned countries. The patient care
must be accompanied by a monitoring and vector control effort, which
would allow the eradication of insects
that transmit the parasite of Chagas
disease.
This disease, in its chronic stage, may
cause cardiac complications and / or
digestive in 20-30% of cases. Because
of cardiac complications (arrhythmias
and heart failure) approximately 10,000
people die annually.
Nowadays, the lack of human resources and strong health infrastructures are the main barriers to guarantee
access to diagnosis and treatment for
patients. These should go together with
promotion and education programs for
both the population and health professionals.
Similar to many parasitic diseases,
Chagas disease is related to population’s low economic and social development. Thus, triatomine insects and
diseases they transmit will exist as long
as depressed housing persists in Latin
America.
Improving these conditions of life would
be the best weapon to combat this
and many other endemic diseases.
CONGRESS
From 29-31 May 2013 it was held
the XVII Congress of the Spanish
Society of infectious diseases
and clinical microbiology.
www.berenice-project.eu
2
Berenice Project - Newsletter
Chagas disease represents
the second highest burden
of disease among Tropical
Diseases in the Americas.
Issue 01 - june 2013
Simplified diagnostic tools and
better treatment adapted to
different needed to combat
Chagas disease.
Promising novel treatments for
chagas disease based on nano
drug delivery systems
N
anomedicine is the innovative
application of nanotechnology
to the diagnosis, prevention,
and treatment of disease in the human
body. Usually, this kind of deep innovation has being fully applied only for diseases affecting developed countries.
But this technology can be applied to
fight several neglected parasitic diseases, like Chagas, that affect hundreds of millions of people and result in
high morbidity and
mortality worldwide.
Efforts
to
reach
that goal are being
made, with projects
like BERENICE being
an example. Efficient
Nano-Drug Delivery
Systems (DDSs) are
of great interest for
neglected diseases
treatment. This approach allows tuning
up existent, low efficient and no safe
treatments, as a way to obtain novel
treatments but avoiding the extremely
high costs related to novel compounds
discovery , which is a critical aspect in
the scarcity of novel therapeutics for
neglected diseases like Chagas.
These advantages derived from the use
of nanocarriers are especially interesting in the treatment of Chagas disease,
as the only current existent treatment
(Benznidazol©) presents significant side
effects and low efficacy for treatment
of the chronic phase of the disease.
1.
Small Unillamelar Vesicles (SUVs),
which constitute one of the most
promising drug nanocarriers in
the field of drug delivery and
Nanomedicine, will be conjugated
to Benznidazole. The use of compressed fluids like CO2 has shown
to provide very effective methodologies for the robust and environmental respectful preparation of
this kind of nanoparticulated conjugates. SUVs obtained using this
methodology present finely tuned
size distributions, highly homogeneous supramolecular structure
and morphology and an acute
response to external stimuli, factors
which improve their pharmacological properties.
2.
SLN´s (Solid Lipid Nanoparticles)
is other possible nanoformulation
of this triazols that could increase
the activity and reduce the toxicity of Benznidazol by providing a
sustained release formulation of
the drug. SLNs are colloidal carrier
systems made from solid lipids, introduced at the beginning of the
nineties as drug delivery systems alternative to existing colloidal carriers. Excellent tolerability, increased
drug stability, reduced citotoxicity
and possibility of qualified industrial
large scale production are clear
advantages of SLN.
New developments in innovation
based on lipid nanoformulations would
alleviate the limitations of current
Chagas treatments.
It is expected to
improve the pharmacokinetics
and
pharmacodynamics
of current Chagas
disease therapies by
decreasing the total
dose of drug used,
minimizing the toxicity profile, reducing
the appearance of
resistance and increasing the tissue
concentration.
In the framework of BERENICE project,
two groups of CIBER-BBN, NANOMOL
and NANOBIOCEL, will develop new
methodologies for preparing formulations which are based on:
Berenice Project - Newsletter
3
PARTNERS
Spain
Argentina
Brasil
France
Portugal
Project Coordinator
Israel Molina
P. de la Vall d’Hebron, 119-129
08035 Barcelona, SPAIN
Phone: +34 93 274 62 51
Email: [email protected]
Project Manager
Esperanza Esteban
P. de la Vall d’Hebron, 119-129
08035 Barcelona, SPAIN
Phone: +34 93 274 60 00 (Ext. 64 73)
Email: [email protected]
For further information, please visit our website at:
www.berenice-project.eu
4
Berenice Project - Newsletter
Facing Chagas by the pharma
industry: the need for open
innovation
Neglected diseases, like Chagas,
mean a major health problem for a
significant number of people, generally located in pour resource setting
and endemic zones, mostly Central
and South America, Africa and parts
of Asia. There exist different definitions
for neglected diseases, but the fact is
that they afflict more than 1400 million
people worldwide. Many of them live
on less than $1.25 per day. Neglected
diseases are linked to poverty, bad
hygienic conditions, lack of access
to clean water, extremely low quality
buildings, and, in many cases, scarcity
of access to adequate treatments for
patients suffering this kind of diseases.
This difficult of access to treatment is
due to several conditions: scarcity of
economic resources, difficulties for distribution due to lack of infrastructures
and no existence of efficient, actualized treatments. The improvement of
living conditions led to eradication of
these diseases in places where people
has access to good health services
and a reasonable standard of living.
Consequently,
efforts for development
of novel treatments
has been discontinued for decades, as
Pharmaceutical industry and capacity for innovation is established
in the no affected
countries.
The described situation
leads to an “innovation
gap”, motivated by the
lack of purchasing power which would
drive the investment in novel medicines
to treat neglected diseases. Chagas is
a paradigmatic example of this situation, as only two treatments exist currently (Benznidazol and Nifurtimox),
both of them discovered more than 40
years ago, when pharmaceutical development was conditioned by the existent technological level and clinical
trials, side effects evaluation, etc, were
less strict than nowadays. Connected
to this innovation scarcity, market
problems have also raised, leading to
definitively stop the production and
sale of Nifurtimox and causing that
Benznidazol production was discontinued for some months, until laboratory
Elea took the responsibility of re-start
the production of this drug, which,
even if it is not ideal, is the best currently
existent weapon against the disease.”
Fortunately, during the last decade
this situation is changing. Efforts from
private and public initiatives (DNDi, Bill
and Melinda Gates Foundation, the
European Commission, Mundo Sano,
CyCA-Ciencia y Conocimiento en
Acción Foundations, etc), together with
a major compromise from the Pharma
industry, is leading to the development
of novel treatments for neglected diseases. The industry is conscious of the
demands of the world of neglected
diseases, and is getting more and more
compromised with the problem, due to
social responsibility convincement, personal compromise of the major shareholders (as happens
with Praxis and Chagas
disease) and opportunities to face projects
prioritized by unmet
medical needs and
no commercial benefit. This new approach
should be faced using
open innovation paradigms, which means
developing
solutions
through collaboration
with different partners,
sharing technology, intellectual property, knowledge, etc, allowing the obtaining of solutions with low cost and
lower risk. BERENICE project is a clear
example of this strategy, putting together clinicians, academics and industry in order to obtain a lower cost,
more efficient and safer treatment for
Chagas disease.