Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa

Instituto Di Ricerche Di Biologia Molecolare P. Angeletti

Anna De Martis

Ralph Laufer

Annalise Di Marco

Isabelle Gloaguen

Riccardo Cortese

Gennaro Ciliberto

Giacomo Paonessa

Domenico Lazzaro

Isabella Saggio

Patrizia Costa

The subject of the present invention are variants of ciliary neurotrophic factor with enhanced receptor selectivity (CNTFR), useful for the treatment of diseases and disorders including motor neuron diseases and muscle degenerative diseases. Another subject of the invention is to provide a method for identifying the above mentioned CNTF variants. The hCNTF variants with the amino acid substitutions in accordance with the present invention, have a reduced ability, as compared to the human CNTF, to elicit biological effects through soluble CNTFR, without affecting its ability to activate membrane-bound neuronal CNTF receptors, thereby improving its therapeutic properties. FIG. 1 shows the reduced CNTFR binding affinity of a CNTF variant according to the invention (IA-CNTF; SEQ ID NO: 2). It is evident that the binding affinity of this variant to the CNTFR is reduced as compared to the wild-type human CNTF molecule.

Variant of ciliary neurotrophic factor and DNA encoding the variant

The present invention refers to the use of hCNTF (human ciliary neurotrophic factor), mutants thereof or other molecules that activate the CNTF receptor, for the preparation of drugs for the treatment of obesity and associated disease, for example hyperglycemia. FIG. shows the anti-obesity effect of hCNTF and leptin on body weight (left panels) and on food intake (right panels) in genetically obese mice and in mice with diet-induced obesity (DIO).

Use of CNTF (ciliary neurotrophic factor) receptor activators for the treatment of obesity

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Rome, Italy

Anna De Martis