The Salk Institute for Biological Studies

The University of Sydney

Annette R Atkins

Ronald Mark Evans

Michael Downes

Ruth T Yu

Jae Myoung Suh

Eiji Yoshihara

John F W Keana

Christopher Liddle

Thomas J Baiga

Sungsoon Fang

Zong Wei

Sagar P Bapat

Ye Zheng

Yasuyuki Kida

Teruhisa Kawamura

Senyon Choe

Sihao Liu

Witek Kwiatkowski

Michael R Downes

Ronald M Evans

John FW Keana

The invention features compositions and methods treating or preventing for age-related insulin resistance, type 2 diabetes and related disorders. The method involves depleting fTreg cells with an anti-ST2 antibody to decrease age-related fTreg accumulation and restore insulin sensitivity, thereby treating age-related insulin resistance, type 2 diabetes and related disorders.

Compositions and methods for treating age-related diabetes and related disorders

The invention features compositions comprising in vitro generated beta cells capable of glucose-stimulated insulin secretion, methods of inducing beta cell maturation from embryonic or induced pluripotent stem cell-derived beta-like cells, and methods of using in vitro generated beta cells for the treatment of type 1 diabetes, type 2 diabetes, or a related disorder.

Compositions and methods for treating type 1 and type 2 diabetes and related disorders

The invention generally features compositions comprising induced pluripotent stem cell progenitors (also termed reprogramming progenitor cells) and methods of isolating such cells. The invention also provides compositions comprising induced pluripotent stem cells (iPSCs) derived from such progenitor cells. Induced pluripotent stem cell progenitors generate iPSCs at high efficiency.

Reprogramming progenitor compositions and methods of use thereof

The invention features pancreatic islet and pancreatic organoids, and cell cultures and methods that are useful for the rapid and reliable generation of pancreatic islet and pancreatic islet organoids. The invention also features methods of treating pancreatic diseases and methods of identifying agents that are useful for treatment of pancreatic diseases, such as type 2 diabetes and pancreatic cancer, using the pancreatic islet and pancreatic organoids of the invention.

Compositions and methods for organoid generation and disease modeling

The present disclosure provides FGF1 mutant proteins, which selectively bind to/activate FGFR1b. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed FGF1 mutants to reduce blood glucose in a mammal and treat a metabolic disorder are provided.

Fibroblast growth factor 1 (FGF1) mutant proteins that selectively activate FGFR1B to reduce blood glucose

Novel compounds having a formula embodiments of a method of making the same, and of a composition comprising them are disclosed herein. Also disclosed are embodiments of a method of treating or preventing a metabolic disorder in a subject, comprising administering to a subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and treating or preventing a metabolic disorder in the subject. Additionally disclosed are embodiments of a method of treating or preventing inflammation in an intestinal region of a subject, comprising administering to the subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and thereby treating or preventing inflammation in the intestinal region of the subject.

Analogs of fexaramine and methods of making and using

Methods are provided for reducing blood glucose, which utilize an agent that increases the biological activity of a vitamin D receptor (VDR) (e.g., a VDR agonist), in combination with an antagonist of bromodomain-containing protein 9 (BRD9). IN some examples, such methods treat type II diabetes.

Use of bromodomain-containing protein 9 antagonists in combination with vitamin D receptor agonists in diabetes treatment

The invention generally features compositions comprising induced pluripotent stem cell progenitors (also termed reprogramming progenitor cells) and methods of isolating such cells. The invention also provides compositions comprising induced pluripotent stem cells (iPSCs) derived from such progenitor cells. Induced pluripotent stem cell progenitors generate iPSCs at high efficiency. In particular embodiments the invention is predicated upon increased expression of an estrogen related receptor and changes in the oxidative and glycolytic pathways.

Reprogramming progenitor compositions and methods of use therefore

Methods of using FGF1 analogs, such as FGF1 mutant proteins having an N-terminal deletion, point mutation(s), or combinations thereof, to reduce blood glucose levels in subjects with steroid-induced diabetes, hypercortisolemia, or diabetes due to treatment with an antipsychotic agent, are provided. Such mutant FGF1 proteins can be part of a chimeric protein that includes a &#x3b2;-Klotho-binding protein, an FGFR1-binding protein, a &#x3b2;-Klotho-binding protein and a FGFR1-binding protein, a C-terminal region from FGF19 or FGF21.

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La Jolla, CA, United States of America

Annette R Atkins