Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw

Life Sciences Research Partners Vzw

Thrombogenics Nv

K.u. Leuven Research & Development

Flanders Interuniversity Institute for Biotechnology

D. Collen Research Foundation Vzw

D. Collen Research Foundation

Collen Research Foundation Vzw

Viaams Interuniversitair Instituut Voor Biotechnologie Vzw

Vib Vzw

Life Sciences Research Partners

Désiré Collen

Peter Carmeliet

Jean-Marie Stassen

Bert Oosthuyse

Roger Bouillon

Sandro De Falco

Ruvo Menotti

Gertrudis Carmeliet

Edward M Conway

Jean Marie Stassen

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

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 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

The present invention relates to the field of pathological angiogenesis and arteriogenesis and, in particular, to a stress-induced phenotype in a transgenic mouse (PIGF) that does not produce Placental Growth Factor (PIGF) and that demonstrates an impaired vascular endothelial growth factor (VEGF)-dependent response. PIGF deficiency has a negative influence on diverse pathological processes of angiogenesis, arteriogenesis and vascular leakage comprising ischemic retinopathy, tumor formation, pulmonary hypertension, vascular leakage (edema formation) and inflammatory disorders. The invention thus relates to molecules that can inhibit the binding of PIGF to its receptor (VEGFR-1), such as monoclonal antibodies and tetrameric peptides, and to the use of these molecules to treat the above-mentioned pathological processes.

Inhibitors of placental growth factor for the treatment of pathological angiogenesis, pathological arteriogenesis, inflammation, tumor formation and/or vascular leakage

This invention relates to antagonists of placental growth factor and signalling thereof, pharmaceutical compositions containing such antagonists and the use of such antagonists to prevent bone loss or bone mass and to enhance bone healing including the treatment of conditions which present with low bone mass and/or bone defects in vertebrates, and particularly mammals, including humans.

Placental growth factor as a target for the treatment of osteoporosis

The in vivo role of the N-terminal lectin-like domain of thrombomodulin was studied by using homologous recombination in murine ES cells to create mutant mice that lack this region of thrombomodulin. Phenotypic analysis shows that said mice respond identically to their wild type littermates following pro-coagulant challenges meaning that the protein C pathway is not altered by the mutation. However, following several inflammatory stimuli, it was observed that the mutant mice showed an elevated neutrophil extravasation in several organs. It is found that leukocyte adhesion could be abrogated by addition of recombinant lectin-domain meaning that said domain has direct anti-inflammatory properties which means that the lectin-like domain can be used to manufacture a medicament useful for the treatment of a variety of inflammatory disease processes.

Lectin-like domain of thrombomodulin and its therapeutic use

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.

Growing community of inventors

Winksele, Belgium

Désiré Collen