Life Sciences Research Partners Vzw

Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw

Vib Vzw

Thrombogenics Nv

Flanders Interuniversity Institute for Biotechnology

D. Collen Research Foundation Vzw

Sanofi

Ludwig Institute for Cancer Research Limited

Universiteit Gent

Vrije Universiteit Brussel

K.u. Leuven Research & Development

Katholieke Universiteit Leuven, Ku Leuven R&d

F. Hoffmann-la Roche Ag

Life Sciences Research Partners

Vib Vzm

Peter Carmeliet

Désiré Collen

Jean-Marie Stassen

Bert Oosthuyse

Desire Collen

Ulf Eriksson

Roger Bouillon

Joost Schymkowitz

Sandro De Falco

Frederic Rousseau

Corentin Herbert

Xuri Li

Désiré J Collen

Diether Lambrechts

Massimiliano Mazzone

Frederik De Smet

Isabelle Colle

Anja Geerts

Julián Aragonés López

Frédéric Rousseau

Ruvo Menotti

Paul Delmar

Gertrudis Carmeliet

Veerle Compernolle

Sonja Loges

Marc Tjwa

Jean Marie Stassen

Sandra Schoors

Dorothee Foernzler

Stefan Scherer

The present application relates to the field of leukemias, and more in particular to how P1 GF inhibition can help to treat Philadelphia chromosome positive (Ph+) leukemias. Methods are provided for treating Ph+ leukemias by administering P1 GF inhibitors. Also disclosed are uses of P1 GF inhibitors in the treatment of Ph+ leukemias, or for the preparation of a medicament against Ph+ leukemias.

Inhibition of PLGF to treat philadelphia chromosome positive leukemia

The present invention relates to an extracellular binding domain for an allosteric inhibitor, whereby said binding domain is derived from a single membrane span tyrosine kinase receptor. More specifically, the invention relates to an extracellular domain derived from a Fibroblast Growth Factor Receptor (FGFR). It further relates to the use of this domain for the identification of similar domains in the extracellular part of other tyrosine kinase receptors, and to a screening method for identification of a small compound allosteric inhibitor.

Extracellular allosteric inhibitor binding domain from a tyrosine kinase receptor

The present invention provides novel monoclonal antibodies directed to PlGF and fragments and derivatives thereof, more particularly to humanized antibodies and fragments thereof for use in the treatment and/or prevention of pathological angiogenesis.

Anti-angiogenic therapy

A key function of blood vessels, to supply oxygen, is impaired in tumors because of abnormalities in their endothelial lining. PHD proteins serve as oxygen sensors and may regulate oxygen delivery. Therefore the role of endothelial PHD2 in vessel shaping by implanting tumors in PHD2mice was studied. Haplodeficiency of PHD2 did not affect tumor vessel density or lumen size, but normalized the endothelial lining and vessel maturation. This resulted in improved tumor perfusion and oxygenation, and inhibited tumor cell invasion, intravasation and metastasis. Haplodeficiency of PHD2 redirected the specification of endothelial tip cells to a more quiescent phenotype of a filopodia-lacking 'phalanx' cell type. Without being bound to a particular mechanism, this transition could at least in part be explained by upregulation of (soluble) VEGFR-1 and VE-cadherin. Thus, decreased activity of an oxygen sensor in hypoxic conditions prompts endothelial cells to readjust their shape and phenotype to restore oxygen supply. Inhibiting PHD2 may offer alternative therapeutic opportunities for anti-cancer therapy, or other therapies where vascular normalization is beneficial.

PHD2 inhibition for blood vessel normalization, and uses thereof

Described are methods of modulating stem/progenitor cell recruitment involving molecules that agonize the formation of plasmin stimulating the recruitment of stem/progenitor cells, including hematopoietic and endothelial precursor cells. Conversely, antagonists of plasmin can inhibit recruitment of the stem cells. In addition, the identification of the uPA receptor (uPAR) as a retention signal for stem cells in their niche suggests a novel method for increased engraftment and isolation of multipotent stem cells.

Means and methods for the recruitment and identification of stem cells

The present invention relates to neurological and physiological dysfunction associated with neuron disorders. In particular, the invention relates to the involvement of vascular endothelial growth factor (VEGF) and homologues in the aetiology of motor neuron disorders. The invention further concerns a novel, mutant transgenic mouse (VEGF) with a homozygous deletion in the hypoxia responsive element (HRE) of the VEGF promoter which alters the hypoxic upregulation of VEGF. These mice suffer severe adult onset muscle weakness due to progressive spinal motor neuron degeneration which is reminiscent of amyotrophic lateral sclerosis (ALS)&#x2014;a fatal disorder with unknown aetiology. Furthermore, the neuropathy of these mice is not caused by vascular defects, but is due to defective VEGF-mediated survival signals to motor neurons. The present invention relates in particular to the isoform VEGFwhich stimulates survival of motor neurons via binding to neuropilin-1, a receptor known to bind semaphorin-3A which is implicated in axon retraction and neuronal death, and the VEGF Receptor-2. The present invention thus relates to the usage of VEGF, in particular VEGF, for the treatment of neuron disorders and relates, in addition, to the usage of polymorphisms in the VEGF promotor for diagnosing the latter disorders.

Use of VEGF and homologues to treat neuron disorders

Anti-PLGF antibody

The present invention relates to the field of liver diseases, more particularly to the field of portal hypertension and liver cirrhosis. The invention relates to the use of molecules which can inhibit the binding of placental growth factor (PIGF) to its receptor (VEGFR-1), such as monoclonal antibodies, for the manufacture of a medicament to treat liver cirrhosis, portal hypertension and its complications.

Treatment of liver cirrhosis and its complications

The present invention relates to the treatment of motoneuron diseases. More particularly, the invention relates to the treatment of amyotrophic lateral sclerosis (ALS). It is found that the intracerebroventricular delivery of low amounts of vascular endothelial growth factor into a pre-clinical ALS animal model induces a significant motor performance and prolongation of survival time of the animals.

Treatment of amyotrophic lateral sclerosis

The invention relates to the field of muscle pathologies, more particularly to the field of diseases where skeletal muscle degeneration occurs. The invention describes transgenic mice that do not produce prolyl-hydroxylase-1, -2 or -3. It is revealed that the phenotype of the prolyl-hydroxylase 1 knock-out mouse is characterized by a protection of skeletal muscle atrophy due to a variety of muscle damages, especially ischemic insults. The invention thus relates to the use of molecules that can bind to prolyl-hydroxylase-1 for the prevention and/or treatment of skeletal muscle degeneration.

Inhibitors of prolyl-hydroxylase-1 for the treatment of skeletal muscle degeneration

The present invention relates to prevention and treatment of strokes and ischemic diseases and to post-ischemic therapeutic treatment. The invention furthermore relates to the use of a growth factor or nucleic acids ensuring increased expression of a growth factor for treating, more particularly restoring the function of ischemic tissue, in particular muscles such as myocardium and skeletal muscles.

Use of placental growth factor for treating ischemic muscle disease

VEGF-B is shown to be needed for cardiac muscle revascularization after heart infarction, and methods of promoting or stimulating vascular development, e.g. angiogenesis and/or arteriogenesis, particularly in ischemic mammals, are disclosed.

Stimulation of vascularization with VEGF-B-186

The present invention relates to the treatment of motoneuron diseases. More particularly the invention relates to the treatment of amyotrophic lateral sclerosis (ALS). It is found that the intracerebroventricular delivery of low amounts of vascular endothelial growth factor into a preclinical ALS animal model induces a significant motor performance and prolongation of survival time of said animals.

Growing community of inventors

Blanden, Belgium

Peter Carmeliet