Growth factor mutants with altered biological attributes

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This invention concerns novel recombinant mutant growth factors from the TGF-β (transforming growth factor-beta) superfamily, specifically mutated at a critical amino acid position to confer new antagonistic (inhibitory) biological properties. By introducing a proline residue into certain positions of proteins like GDF-5 and related bone morphogenetic proteins (BMPs), these mutants inhibit the normal action of BMPs, allowing control over cell differentiation and growth. The invention covers these proteins, the DNA that encodes them, host cells, pharmaceutical compositions, and their use in various therapies, especially those involving abnormal bone, muscle, or tissue growth and regeneration.

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• Therapeutic treatments for diseases caused by excessive bone and tissue formation (e.g., fibrodysplasia ossificans progressiva, sclerosteosis, progressive osseous heteroplasia, osteoma cutis, myositis ossificans, arterial sclerosis).
• Supportive therapy for muscular diseases and conditions involving muscle wasting or weakness (e.g., Duchenne muscular dystrophy, ALS, cardiac insufficiency, AIDS-related muscle weakness, age-related muscle atrophy).
• Prevention or treatment of disorders linked to excessive BMP signaling, such as ectopic ossification post-surgery, ossification of heart valves, and cancer-induced aberrant angiogenesis.
• Control and direction of stem cell and progenitor cell differentiation, especially to promote muscular rather than bone cell fates in regenerative medicine and cell therapy.
• Modulation of tissue regeneration for organs, muscles, or connective tissue post-injury or in degenerative diseases.
• Replacement of natural BMP antagonists (e.g., Noggin, Chordin) where their activity is insufficient, for therapeutic interventions.
• Use in research and drug development to investigate signaling pathways and cellular responses regulated by the TGF-β superfamily.
• Potential applications in tissue engineering, including controlled formation of muscle or inhibition of excess bone formation in engineered tissues.

BenefitsContent extracted from patent full text and abstract with AI.

• Provides a targeted approach to inhibit excessive or unwanted bone and tissue growth by antagonizing BMP activity.
• Enables fine control of cell differentiation, allowing promotion of muscle over bone formation, which is valuable in regenerative medicine and treatment of muscular diseases.
• Offers therapeutic options for currently untreatable or difficult-to-treat disorders related to abnormal ossification or muscle degeneration.
• Extends to a wide variety of applications including gene therapy (using vectors/host cells), antibody therapy, and cell therapy.
• Can be used to modulate tissue regeneration and repair after injury, surgery, or degenerative disease, improving recovery and functional outcomes.
• Potential to replace or supplement endogenous BMP antagonists in diseases where natural mechanisms are insufficient.
• Versatile: the invention covers proteins, encoding DNA, vectors, host cells, pharmaceutical compositions, and diagnostic or research tools.
• May reduce side effects compared to less specific, systemic treatments for disorders characterized by overactive BMP signaling.

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Patent Abstract

The invention relates to novel recombinant growth factor mutants with altered biological attributes which are derived from proteins of the TGF-² superfamily of signalling molecules and exhibit novel antagonistic properties. They are particularly suitable for the determination of cell fates, the growth stimulation and differentiation of various cells including stem cells and the regeneration of organs. They are also useful for the supportive therapy of muscular diseases and treatment of disorders characterized by the excessive action of TGF-² superfamily members.