The researchers found that the number of hairs on flies’ legs varies according to the level of activity of a so-called microRNA.  The results, published in the journal Current Biology, shed a completely new light on the molecular mechanisms of evolution.

It has long been known that certain proteins, known as transcription factors, directly control the way in which information is read from DNA.  As a result, it is widely believed that changes in genes encoding such proteins underlie the mechanisms responsible for evolutionary adaptation.  The idea that small RNA molecules, so-called microRNAs, may play an important part in evolutionary changes to animals’ appearance is completely new.  An international team of researchers, including Christian Schlötterer and Alistair McGregor from the Institute of Population Genetics of the University of Veterinary Medicine, Vienna (Vetmeduni Vienna), has now published a study that describes such an evolutionary mechanism.

Small and large bald patches

Insect bodies are generally covered with a large number of microscopic hairs.  This is the case for the legs of many closely related species of the fruit fly genus Drosophila, although the animals have a bald patch on the second pair of legs, intriguingly known as the naked valley.  Previous work had shown that the size of this patch is regulated by the gene ultrabithorax (Ubx) and that it differs between species.  However, the work at the Vetmeduni Vienna showed that similar differences are shown by individuals from different populations of Drosophila melanogaster.

Their search for the genetic basis of the variation led the researchers to a segment of fruit fly DNA that contained four genes.  Three of these genes were known to encode proteins with no role in the development of the hairs.  The fourth gene, known as miR-92a, encodes a microRNA.  Previous experiments had shown that an increase in activity of the miR-92a gene was associated with a loss of hairs from the animals’ wings.  By overexpressing the gene in the legs of the fruit flies, the scientists were able to cause hair loss on the animals’ legs.

Schlötterer is naturally excited by the findings.  “This is the first experiment to show that natural variation in the expression of a microRNA can lead to a change in the appearance of an organism.  MicroRNAs can fine-tune the level at which genes are expressed, so evolutionary changes in the production of microRNA would be an elegant way to cause morphological changes.”

The article “Evolution of mir-92a Underlies Natural Morphological Variation in Drosophila melanogaster” by Saad Arif, Sophie Murat, Isabel Almudi, Maria D.S. Nunes, Diane Bortolamiol-Becet, Naomi S. McGregor, James M.S. Currie, Harri Hughes, Matthew Ronshaugen, Élio Sucena, Eric C. Lai, Christian Schlötterer and Alistair P. McGregor appeared in the journal “Current Biology” (23(6), pp.523-528).

The same issue of Current Biology (23(6) includes on pp. R247-R249 a commentary on the article by Artyom Kopp (Department of Ecology and Evolution, University of California Davis, USA) under the title “Evolutionary Genetics: Big Effect of a Small RNA”.

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Automatic exchange of Intercell shares

On the expected closing date May 28, 2013, Intercell shareholders will receive 13 new ordinary shares and 13 new preferred shares of Valneva for every 40 Intercell shares (ISIN AT0000612601) that they own. The exchange of the shares will be executed automatically and without costs for shareholders. Fractional entitlements of less than one new Valneva share will be sold on the stock market and proceeds will be credited to each shareholders account free of all charges. Vivalis shares (ISIN FR0004056851) will not be affected by any share exchange and continue to exist under the new name of Valneva. The Valneva shares will be traded on both the NYSE Euronext Paris and the Vienna Stock Exchange.

Share trading on the Vienna Stock Exchange

Intercell shares will be suspended from trading on the Vienna Stock Exchange at close of business of May 21, 2013 in order to enable the settlement of all orders before the exchange into Valneva ordinary and preferred shares. Valneva ordinary shares (ISIN FR0004056851) will start trading in the Prime Market segment of the Vienna Stock Exchange on May 28, 2013 under the ticker symbol “VLA” and will continue to be listed on the regulated market of NYSE Euronext in Paris under the ticker symbol “VLS.PA”. Valneva preferred shares (ISIN FR0011472943) will start trading on May 28, 2013 on the regulated market of NYSE Euronext in Paris under ticker symbol “VLSpr.PA” and on the unregulated Third Market Segment of the Vienna Stock Exchange under the ticker symbol “VLAP”.

Our Annual Report provides information on our activities and results in 2012 while giving you an outlook on the fiscal year 2013.

You can order a hardcopy of the Intercell Annual Report 2012 here: http://www.intercell.com/main/meta/contact/

Things stay fresh longer when refrigerated. That goes for lettuce as well as humans – especially when the body is not provided with an adequate supply of oxygen. This occurs following sudden cardiac arrest, which has a survival rate of less than ten percent. Cooling to 33 degrees Celsius – known as mild hypothermia – is actually the only effective therapy for improving the survival rates of these patients. A team of researchers from the Medical University of Vienna will now investigate how to improve hypothermic treatment when using it in combination with invasive resuscitation procedures.

RESUSCITATION & REPAIRING 

Hypothermia works by reduction of reperfusion injury – the damage that is inflicted by oxygenized blood flowing into oxygen-deprived tissue. As paradoxical as it may sound, the resuscitation that makes survival of the patient possible, likewise leads to damage of the heart muscle and brain. Dr. Andreas Janata from the Department of Emergency Medicine at the Medical University of Vienna and leader of the project on this topic: “Reperfusion injury occurs when blood flow is restored to the brain after a period of hypoxia, which is oxygen deprivation. Restoration of the blood flow actually triggers an inflammation reaction and oxidative stress that can damage the tissue. Hypothermia can reduce the effects of these mechanisms of damage.” Current conventional protocols involve reducing the body temperature down to 33 degrees Celsius. According to the hypothesis, even lower temperatures would minimise damaging after-effects in the brain – but they would lead to intolerable side effects for the heart.

Dr. Janata and his team want to get a grip on precisely this treatment dilemma. For invasive resuscitation procedures using a heart-lung machine relieve the heart during resuscitation and thus allow the use of lower temperatures. However, the best temperature scheme is not yet known and the project will settle this.

THERAPEUTIC COCKTAIL “ON THE ROCKS” 

Hypothermia influences a great many physiological processes, which is one of the challenges involved. These include programmed cell death (apoptosis), immune responses, and damage to nerve cells (excitotoxicity), as well as oxidative cellular stress. The processes affected are actually so complex that it would be difficult to identify any one single pharmaceutical therapy that could have just as comprehensive and positive an effect as hypothermia does. Dr. Janata comments: “Hypothermia is like a cocktail of various medications. That makes it very difficult to study its effect or determine the best practices for treatment.” Due to this complexity, a significant part of the work begun recently by his team consists of setting up a suitable multi-tier model that permits analysis of various treatment regimens.

In fact, the team had already managed to develop models for ventricular fibrillations and invasive resuscitation some time ago. The project will now include developing neuro-behavioural tests for this model. These tests will be carried out following an induced circulatory arrest and permit the consequences of treatments with varying degrees of hypothermia during invasive resuscitative procedures to be compared. The results of this project, which is supported by the FWF, will then offer a basis for best-practices treatment in cases of sudden cardiac arrest – a medical problem that has exhibited frighteningly low survival rates, despite its frequent occurrence.

AP301 is synthetic peptide which has been shown in animal studies in rats and pigs following application by inhalation of the nebulised compound, to prevent and treat ischemia reperfusion injury, to significantly improve gas exchange in pre-damaged donor lungs and to activate lung oedema reabsorption. Until today, no medicinal product has been specifically authorized by medicines agencies for prevention and treatment of primary graft dysfunction / ischemia reperfusion injury in the lung following lung transplantation.

The interventional, randomized, placebo-controlled, parallel-group study entitled “Pilot study to investigate the clinical effect of orally inhaled AP301 on treatment of primary graft dysfunction (PGD) in mechanically ventilated patients after primary lung transplantation” will be conducted at the Vienna General Hospital and the Medical University of Vienna, Austria. Immediately after lung transplantation, patients will be screened for early signs of primary graft dysfunction. Patients who are included into the study will receive doses of AP301 or matching placebo converted into an aerosol by state-of-the-art nebuliser technology over a period up to 7 days.

“We are very pleased that the Ethics Committee has approved our study” said Bernhard Fischer, CEO of APEPTICO. “Prevention and treatment of primary graft dysfunction represents an unmet medical need as no specific therapy or medicinal product has been approved so far for this life-threatening condition. Having successfully completed our Phase I clinical trial in 2011, this is our second Phase II clinical study in pulmonary patients. We initiated a Phase II clinical study in patients suffering from oedematous respiratory failure (ALI/ARDS) in summer 2012 and the new clinical study in lung transplantation patients broadens the therapeutic application of our lead compound AP301.”

About APEPTICO GmbH (www.apeptico.com)

APEPTICO is a privately-held biotechnology company based in Austria, developing peptide-based products targeting chronic and life-threatening diseases. The peptide molecules correspond to validated, pharmacodynamic active structures and domains of well-known proteins and biopharmaceuticals. By concentrating on synthetically produced protein structures APEPTICO avoids general risks associated with gene- and cell-technologies. APEPTICO makes use of its technology platforms PEPBASETM and PEPSCREENTM to significantly reduce cost and to shorten time to market.

About AP301 peptide family

AP301 and derived peptides are synthetic molecules whose structures are based on naturally occurring motifs. AP301 peptides are water soluble and can be administered into the lung by oral inhalation. Formulated AP301 is easily nebulised and the resulting aerosol is composed of peptide/water droplets of diameter 4 μm or less. AP301 and derived peptides are designed for activation of the pulmonary epithelial sodium channel (ENaC). Activation of ENaC by AP301 results an accelerated lung oedema clearance in the airspace. Comprehensive research and development conducted by APEPTICO has demonstrated that AP301 peptides are effective in animal models of various forms of pulmonary oedema, including high altitude pulmonary oedema, acute lung injury / acute respiratory distress syndrome, pneumonia, influenza virus lung infection, and lung transplantation. Currently, AP301 is subject to a Phase IIa clinical study for the treatment of patients suffering from life-threatening oedematous respiratory failure.

About Primary Graft Dysfunction

Primary Graft Dysfunction (PGD) / Ischemia Reperfusion Injury (IRI) is characterized by poor oxygenation as the main criterion for the condition and is also characterized by low pulmonary compliance, interstitial/alveolar oedema, pulmonary infiltrates on chest radiographs, increased pulmonary vascular resistance, intrapulmonary shunt and acute alveolar injury, as revealed by diffuse alveolar damage (DAD) on pathology. PGD occurs in approximately 20% of lung transplant recipients and patients face prolonged ventilation, prolonged stays in the ICU and the hospital overall, increased medical costs, and increased risk of morbidity and mortality.

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Activartis has developed a novel patented cancer immunotherapy concept, AV0113, based on dendritic cells (DC).While DCs have already demonstrated their potential in cancer immunotherapy, the novel feature of AV0113 is that exposure to bacterial endotoxins enables the DC to prime type 1 T helper cells, which support cytolytic anti-tumour immune responses. This is comparable to conjugated vaccines, which are a more artificial way to modulate the features of an immune response.

At the beginning of 2013, Activartis completed recruitment of around 100 brain cancer patients for a multi-centre, randomised, phase II clinical trial. This randomised study aims to deliver safety and efficacy data for the first time. Early results do not exhibit an improvement in progression-free survival, but overall survival seems to clearly favour GBM patients.

The study
Activartis has completed recruiting around 100 patients suffering from GBM for the phase II clinical trial (GBM-Vax) designed to provide evidence for the effectiveness of AV0113 cancer immunotherapy. GBM-Vax is being conducted at eight neuro-surgery/neuro-oncology institutions in Austria, three of them being university hospitals. The primary study objective is progression-free survival; the secondary objective is overall survival.

All patients aged 18-70 years receive standard first-line therapy; in the randomised treatment group, the AV0113 DC-CIT is administered as an add-on. The DC-CIT is inoculated into inguinal lymph nodes: after six weeks of chemo and radiotherapy, four weekly applications; accompanying the maintenance chemotherapy, six more applications every 4 weeks; finally one boost immunisation every three months as long as DC-CIT is available.

Preliminary results
Preliminary results presented at the AACR Annual Meeting (April 6-10, 2013, Washington) revealed a very promising trend suggesting a survival benefit of patients in the AV0113 treatment group compared to the randomised control group. This was notably the case for a subgroup for which, although only one third of the patients were available for assessment at this time, the difference in overall survival appeared to be quite remarkable.

At 12 months, 21/33 (64 %) of patients in the treatment group and 17/35 (48 %) of patients in the control group were still alive. At 18 months, 8/15 (50 %) of patients in the treatment and 6/18 (33 %) of patients in the control group were still alive.

Patients receiving AV0113 cancer immunotherapy tended to experience signs of relapse earlier compared to control patients. AV0113-triggered inflammation in the tumour tissue may explain this observation, which was also made in other clinical trials studying cancer immunotherapy.

When tumour growth is controlled by cancer immunotherapy, this is accomplished by inflammation, thereby resulting in a larger oedema and infiltration with immune cells. This may very easily result in pressure-induced neurological symptoms, which then are wrongly interpreted as “progression”. True progression would go along with reduced overall survival – preliminary results of the ongoing study, however, suggest that overall survival may in fact be positively influenced.

AV0113 treatment was well tolerated; no serious adverse events were noted that could clearly be attributed to DC-CIT. Inoculation into inguinal lymph nodes causes local swelling, redness and tenderness; some of the patients ran a temperature of around 40°C. Although these are early data, Activartis has already concluded that the DC-CIT treatment is well tolerated.

Confirmation of that trend is expected in the second half of 2013. If the trend currently observed is confirmed, AV0113 is bound to become part of the standard therapy for GBM.

About Activartis
Activartis is a biotech company based in Vienna. The majority owner is the Austrian pharmaceutical company AOP Orphan Pharmaceuticals AG, which specialises in the development and distribution of pharmaceuticals for Orphan Diseases. Activartis was founded in 2003 as a spin-off of the St. Anna Children’s Cancer Research Institute, Vienna, Austria. Activartis is currently in phase II of clinical trials for a new kind of Cancer Immunotherapy. The therapeutic technology combines a completely new, patented approach, AV0113, that uses a bacterial danger signal together with the patient’s tumour antigens, with the concept of dendritic cells already on the market. The aim is to enable the immune system to gain control of the cancer.
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The race to overcome weaknesses in the cold-chain for vaccine transport and storage is on! Many people in tropical and developing countries cannot benefit from life-saving vaccines because these vaccines are damaged during transport and storage. Many vaccines need to be kept at a cool and stable temperature to remain effective and this is difficult to ensure in these regions.

The European Commission is offering a EUR 2 million prize for innovations which can solve this global health problem.

If you are established as a legal entity in the EU or in a country associated with the 7th Research Framework Programme you can compete for this prize.

The competition is open from 16 April 2012 until 3 September 2013.

For further information have a look at http://ec.europa.eu/research/health/vaccine-prize_en.html

Vienna, 27 March 2013 – The Viennese biotech boutique Themis has reported rapid progress in the development of two highly efficient vaccines against Dengue and Chikungunya fever. In the just concluded preclinical studies, the two vaccine candidates, based on a technology by the Parisian Pasteur Institute, displayed exceedingly good efficacy. With a single vaccination against Chikungunya it was possible to develop full vaccination protection. The Dengue fever vaccine candidate proved effective against all of the four known serotypes of this infection. On the basis of these excellent results, Themis will start the clinical phase I study for both vaccines before the end of this year.

The Viennese biotech company Themis Bioscience GmbH today released data from two preclinical programs for the development of vaccines against Dengue and Chikungunya fever. Both diseases already cause massive problems in tropical countries and, due to increased foreign travel, are also becoming an increasing threat to Western industrialized nations. The currently released data convincingly confirm the technology platform “Themaxyn” developed by Themis: Both of the vaccine candidates for Dengue fever and for Chikungunya fever achieved significantly higher survival rates compared with the control groups.

CEO and founder of Themis, Dr. Erich Tauber commented: “Our Themaxyn platform is based on a standard vaccination against measles. In addition to its excellent safety and production profiles, it has also proven its high efficiency millions of times. We are actually using this vaccine as a kind of Trojan horse: Gene sequences of the pathogens with a length of up to 5,000 base pairs are “smuggled in” and ultimately lead to the immunization of the vaccinated individual.”

The ability to integrate such large sequences in the vector is a blessing for the development of a Dengue fever vaccine. There are four serotypes of the pathogen known worldwide and immunization against one serotype does not protect against infection by another – on the contrary: The probability of serious consequences increases considerably. A truly efficient vaccine against Dengue fever therefore has to protect against all four serotypes at the same time. This is exactly what the vaccine candidate from Themis does, thanks to the possibility of inserting long gene sequences. This means that four epitopes – one from each serotype – can be expressed simultaneously to allow a tetravalent vaccine.

According to Dr. Tauber: “Effective vaccines against Dengue fever must be effective against all four Dengue virus strains. Our technology allows this with a single vector and we have seen very promising data from animal models. Other studies on dosing and administration are currently underway, and the results will go directly into the phase I clinical study which we plan to start before the end of this year.” In addition to this, the Themis team is already developing vaccine candidates of the second generation against Dengue fever – and securing options for itself for the development of vaccines against yellow fever, Japanese encephalitis, West Nile Fever and further undisclosed targets on the basis of the Themaxyn platform.

This means that the development pipeline of the company is currently full to the brim and a substantial target of the corporate strategy has been achieved. The business model of the biotech boutique provides for the continuous and simultaneous development of several vaccine candidates at its Vienna location. Successful candidates will be sold at ideal points of the value-added chain and the revenue reinvested in the company´s own R&D.

About Themis (as of March 2013):

Themis Bioscience GmbH develops vaccines against infectious diseases. The company focuses on emerging tropical infectious diseases and develops vaccines from the preclinical to the early clinical phase. Initial vaccine candidates are currently being developed against Dengue, Chikungunya and yellow fever, with vaccines against other diseases a future possibility. The company´s own Themaxyn technology platform, which has been licensed by the internationally respected Pasteur Institute in Paris, forms the basis for all vaccine candidates of the Vienna-based company. This platform is highly innovative and fully protected by patents.

Contact Themis Bioscience GmbH:

Vienna, Austria, March 18, 2013 / B3C newswire / – Anagrelide a selective platelet lowering agent is not inferior compared to hydroxyurea in preventing disease related complications in patients with WHO-ET. ANAHYDRET study data now provide evidence that anagrelide can be considered as first line therapy for lowering of platelet count in WHO-ET.

High platelet counts in essential thrombocythemia (ET) can be effectively lowered by treatment with either anagrelide or hydroxyurea. However, previous data on this treatment stem from PVSG classified ET and until recently it was still unknown whether existing treatment recommendations could also be applied to ET patients diagnosed according to the contemporary World Health Organization (WHO) classification (WHO-ET). Now, data of the ANAYDRET study confirm anagrelide to be non-inferior to hydroxyurea in the treatment of WHO-ET.

“Our thanks go to the investigators and their staff who participated in this compelling study. I truly believe that these results with anagrelide will translate into clinical benefits for patients with ET”, Dr. Rudolf Widmann, CEO of the sponsor AOP Orphan Pharmaceuticlas AG, Vienna, Austria commented.

In 259 previously untreated, high-risk ET patients, diagnosed according to the WHO classification system, efficacy and tolerability of anagrelide compared to hydroxyurea was investigated in a prospective randomized non-inferiority phase III study in an a-priori ordered hypothesis. Confirmatory proof of non-inferiority of anagrelide was achieved after 6 months using the primary endpoint criteria and further confirmed after an observation time of 12 and 36 months for platelet counts, hemoglobin levels, leukocyte counts (significantly lower in hydroxyurea group due to its non-selective mode of action) (all p<0.001) and ET related events (Hazard Ratio [95%CI]=1.19[0.61-2.30], 1.03[0.57-1.81] and 0.92[0.57-1.46] respectively). During the total observation time of 730 patient-years, there was no significant difference between the anagrelide and hydroxyurea group regarding incidences of major arterial (7 vs. 8) and venous (2 vs.6) thrombosis, severe bleeding events (5 vs. 2), minor arterial (24 vs. 20) and venous (3 vs. 3) thrombosis and minor bleeding events (18 vs. 15), or discontinuation rates (adverse events 12 vs. 15 or lack of response (5 vs. 2). Disease transformation into myelofibrosis or secondary leukemia was not reported.

“I am extremely pleased with the ANAHYDRET study results. With this well designed study, we now have clear evidence for an equi-effective treatment option devoid of the leukemogenic properties of hydroxyurea”, declared Prof. Heinz Gisslinger, Medical University of Vienna, principal investigator on behalf of the ANAHYDRET Study Group.

About ET

Essential thrombocythemia (ET) is a disorder of the bone marrow characterized by a neoplastic overproduction of platelets (thrombocytes). This overproduction of platelets can lead to an increased risk of blood clots (thrombus) and bleeding (hemorrhage). However, with permanent control of platelet numbers, most patients with ET have a near normal life expectancy.

About Anagrelide

Anagrelide (Thromboreductin®) is an oral imidazoquinazoline agent which selectively slows the maturation of platelet precursor cells. Anagrelide is indicated for the reduction of elevated platelet counts in at risk patients with ET.

About Hydroxyurea

Hydroxyurea is a mild cytostatic agent working by antagonizing the production of deoxyribonucleotides (DNA components). Thereby hydroxyurea non selectively slows the proliferation of rapidly growing cells such as blood cells. Hydroxyurea is indicated for the treatment of several neoplastic blood diseases.