Methods and compositions for treating and preventing muscle wasting disorders
Inventors
Lukasiewicz Hagai, Esther • Ofir, Rachel • Fuchs Telem, Dana
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10258652-B2
Publication Date
2019-04-16
Expiration Date
Abstract
Described herein are methods of treating and preventing muscle wasting and muscle loss, using adherent stromal cells and conditioned medium produced thereby.
Core Innovation
The disclosed subject matter relates to methods and compositions for treating, preventing, and inhibiting muscle wasting and/or muscle loss. The approaches use adherent stromal cells (ASC) and conditioned medium (CM) and/or exosomes produced by ASC. The ASC are cultured under 2D and/or 3D conditions, and the resulting ASC-derived products are used to address muscle mass decline associated with muscle wasting syndrome.
The document describes ASC sources and preparations, including placental-derived ASC in which fetal-enriched and maternal-enriched cell populations are distinguished. It further identifies additional tissue sources for ASC. The cultured ASC are characterized by functional and immunologic features, including immune modulation and cytokine secretion profiles, including responses under inflammatory stimulation.
The disclosure includes reporting that placental-derived ASC show differentiation capacity distinct from bone-marrow-derived ASC, including that placental-derived ASC do not osteogenically or adipogenically differentiate under the induction conditions described. The document also reports that ASC suppress lymphocyte proliferation and modulate cytokine secretion, including an increase in IL-10 and a reduction in TNF-α. In a muscular dystrophy mouse model, ASC treatment is reported to reduce creatine phosphokinase and to show trends toward reduced inflammation/necrosis with improved regeneration scores, with additional testing described for other muscle loss contexts such as heart-failure-associated muscle wasting and aging-associated muscle loss.
The disclosure further describes potential medicament formulations using pharmaceutically acceptable carriers and excipients, including freezing and cryoprotectants. It also describes routes of administration including intramuscular injection and intravenous injection, and it includes discussion of culture system features relevant to generating the ASC-derived conditioned medium and/or exosomes, including 3D bioreactors and carriers such as FibraCel® and perfusion-related conditions.
Claims Coverage
Not explicitly described in patent.
Not explicitly described in patent.
Stated Advantages
Treat, prevent, and inhibit muscle wasting and/or muscle loss using adherent stromal cells (ASC) and ASC-derived conditioned medium and/or exosomes.
ASC-based treatment suppresses lymphocyte proliferation and modulates cytokine secretion, including increased IL-10 and reduced TNF-α under inflammatory stimulation.
In a muscular dystrophy mouse model, ASC treatment reduces creatine phosphokinase and shows trends toward reduced inflammation/necrosis with improved regeneration scores.
Placental-derived ASC preparations show differentiation capacity distinct from bone-marrow-derived ASC, including reduced osteogenic/adipogenic differentiation under the induction conditions described.
Documented Applications
Muscular dystrophy-associated muscle wasting/muscle loss, including use in an mdx mouse model with reported effects on creatine phosphokinase, inflammation/necrosis trends, and regeneration scores.
Heart-failure-associated muscle wasting.
Aging-associated muscle loss.
Human treatment and/or assessment endpoints.
Interested in licensing this patent?