Abstract: Recombinant herpes simplex virus (HSV)-1 capable of selectively replicating in alternative lengthening of telomeres (ALT)-dependent tumor cells are described. The recombinant HSV-1 are ICP0-deficient, such as by complete deletion of the ICP0 gene, or mutation of the ICP0 gene sufficient to diminish or eliminate E3 ubiquitin ligase activity of ICP0. In some cases, the recombinant HSV-1 further include additional gene deletions or mutations, such as those that render the virus glycoprotein C (gC) deficient, or include a heterologous gene, such as a gene encoding an immunostimulatory molecule. Methods of treating ALT-dependent cancer, and methods of selectively killing ALT-dependent tumor cells are also described.
Abstract: Provided herein are compounds of formula (I) useful for the treatment of PPAR-delta related diseases (e.g. mitochondrial diseases, muscular diseases, vascular diseases, demyelinating diseases and metabolic diseases).
Type:
Grant
Filed:
October 7, 2015
Date of Patent:
January 29, 2019
Assignees:
Mitobridge, Inc., Salk Institute for Biological Studies
Inventors:
Michael Downes, Ronald Evans, Arthur Kluge, Bharat Lagu, Masanori Miura, Sunil Kumar Panigrahi, Michael Patane, Susanta Samajdar, Ramesh Senaiar, Taisuke Takahashi
Abstract: Methods, systems, and devices are disclosed for acquiring and analyzing physiological signals. In one aspect, a physiological sensor device includes a substrate formed of an electrically insulative material and structured to allow physical contact of the device with the frontal region of the head of a user, a recording electrode configured at a first location on the substrate to acquire an electrophysiological signal of the user, a reference electrode configured at a second location on the substrate to acquire a reference signal to the electrophysiological signal, and a ground electrode configured at a third location at least partially between the first and the second locations on the substrate, in which the first location is posterior to the second and third locations, and in which the device is operable when electrically coupled to an electrical circuit to detect physiological signals of the user.
Type:
Grant
Filed:
October 14, 2013
Date of Patent:
January 22, 2019
Assignees:
The Regents of the University of California, The Salk Institute for Biological Studies
Inventors:
Todd Prentice Coleman, Rui Ma, Michael Bajema, Ricardo Gil Da Costa, Raynard Fung
Abstract: This disclosure reveals that cyclic corticotrophin releasing factor (CRF) antagonist peptides (such as astressin B, its functional fragments, and their derivatives) induce hair growth and prevent hair loss in vivo. This important discovery enables, for instance, methods of promoting hair growth, and methods of treating hair loss (such as the hair loss that occurs normally in some individuals or that is the result of a health disorder or therapeutic treatment). Exemplary cyclic CRF antagonist peptides useful in the disclosed methods are provided throughout the disclosure.
Type:
Grant
Filed:
June 20, 2007
Date of Patent:
January 1, 2019
Assignees:
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, SALK INSTITUTE FOR BIOLOGICAL STUDIES
Abstract: The method provides methods and compositions for treating metabolic disorders such as impaired glucose tolerance, elevated blood glucose, insulin resistance, dyslipidemia, obesity, and fatty liver.
Type:
Grant
Filed:
November 14, 2016
Date of Patent:
December 25, 2018
Assignee:
Salk Institute for Biological Studies
Inventors:
Johan W. Jonker, Michael Downes, Ronald M. Evans, Jae Myoung Suh
Abstract: Recombinant adenovirus genomes that include a heterologous open reading frame (ORF) and a self-cleaving peptide coding sequence are described. The recombinant adenovirus genomes and recombinant adenoviruses produced by the disclosed genomes can be used, for example, in high-throughput assays to measure virus replication kinetics. Methods for measuring replication kinetics of a recombinant adenovirus are also described.
Type:
Application
Filed:
August 22, 2018
Publication date:
December 13, 2018
Applicant:
Salk Institute for Biological Studies
Inventors:
Clodagh O'Shea, William Partlo, Colin Powers
Abstract: Recombinant adenovirus genomes that include an exogenous open reading frame (ORF) and a self-cleaving peptide coding sequence are described. Optimal placement of the exogenous genes for minimal impact on viral kinetics is further disclosed. Therapeutic applications of the recombinant adenoviruses are also described.
Type:
Application
Filed:
August 23, 2018
Publication date:
December 13, 2018
Applicant:
Salk Institute for Biological Studies
Inventors:
Clodagh O'Shea, William Partlo, Colin Powers
Abstract: The present disclosure provides compositions that include a nanoparticle and a compound that reduces the biological activity of one or more bromodomain and extra-terminal family member (BET) proteins (e.g., a bromodomain inhibitor), and methods of using such compounds to increase retention or storage of vitamin A, vitamin D, and/or lipids by a cell, such as an epithelial or stellate cell.
Type:
Application
Filed:
May 18, 2018
Publication date:
November 15, 2018
Applicant:
Salk Institute for Biological Studies
Inventors:
Ronald M. Evans, Michael Downes, Mara Sherman, Ning Ding
Abstract: The present disclosure provides FGF2 mutant proteins, such as those having an N-terminal deletion, point mutation(s), or combinations thereof, which can reduce blood glucose in a mammal. Thus, the disclosed mutant FGF2 proteins can be used to treat one or more metabolic diseases. In some examples, mutant FGF2 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels, for example to treat a metabolic disorder are also provided.
Type:
Application
Filed:
July 13, 2018
Publication date:
November 8, 2018
Applicant:
Salk Institute for Biological Studies
Inventors:
Ronald M. Evans, Michael Downes, Annette Atkins, Ruth T. Yu
Abstract: Provided herein are deuterated compounds and compositions useful in increasing PPAR? activity. The compounds have a formula where L5 comprises at least one deuterium. Exemplary species include The compounds and compositions provided herein are useful for the treatment of PPAR? related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).
Type:
Application
Filed:
June 28, 2018
Publication date:
October 25, 2018
Applicant:
The Salk Institute for Biological Studies
Abstract: 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.
Type:
Application
Filed:
January 12, 2016
Publication date:
September 20, 2018
Applicant:
SALK INSTITUTE FOR BIOLOGICAL STUDIES
Inventors:
SAGAR P. BAPAT, YE ZHENG, RONALD EVANS, MICHAEL DOWNES, ANNETTE R. ATKINS, RUTH T. YU
Abstract: Novel FXR agonists are disclosed, 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.
Type:
Grant
Filed:
September 12, 2016
Date of Patent:
September 18, 2018
Assignee:
Salk Institute for Biological Studies
Inventors:
Ronald M. Evans, Michael Downes, Thomas J. Baiga, John F.W. Keana, Christopher Liddle
Abstract: 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 ?-Klotho-binding protein, an FGFR1-binding protein, a ?-Klotho-binding protein and a FGFR1-binding protein, a C-terminal region from FGF19 or FGF21.
Type:
Application
Filed:
April 13, 2018
Publication date:
August 16, 2018
Applicant:
Salk Institute for Biological Studies
Inventors:
Ronald M. Evans, Michael Downes, Annette Atkins, Ruth T. Yu
Abstract: Synthetic adenoviruses having chimeric fiber proteins and liver detargeting mutations are described. The synthetic adenovirus vectors are capable of specifically infecting cells at wound sites or in regions of damaged tissue. The synthetic adenovirus vectors also are capable of expressing transgenes, such as wound healing factors, at sites of wounded or damaged tissue. Accordingly, the described vectors can be used to detect wounded or damaged tissue, and/or to promote wound healing and regeneration of damaged tissue, such as by expression of heterologous wound healing or tissue regeneration factors.
Type:
Application
Filed:
April 4, 2018
Publication date:
August 9, 2018
Applicant:
Salk Institute for Biological Studies
Inventors:
Clodagh O'Shea, Colin Powers, Lei Zhang
Abstract: Provided herein are deuterated compounds and compositions useful in increasing PPAR? activity. The compounds have a formula where L5 comprises at least one deuterium. Exemplary species include The compounds and compositions provided herein are useful for the treatment of PPAR? related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).
Type:
Grant
Filed:
April 7, 2017
Date of Patent:
July 31, 2018
Assignee:
The Salk Institute for Biological Studies
Abstract: Brown adipose tissue (BAT) plays a role in keeping an organism warm in response to a cold environment. In response to cold, transcription factors, including peroxisome proliferator receptor alpha (PGC1?), mediate the adaptive changes in the expression of oxidative and thermogenic genes in BAT. However, even without cold, BAT exhibits high expression of these genes relative to white adipose tissue (WAT). It is shown herein that estrogen related receptor gamma (ERR?) is a critical factor that controls the expression of key metabolic genes in BAT under basal conditions. ERR? is highly expressed in BAT versus WAT, yet is not transcriptionally induced by cold, suggesting it plays an important role in innate basal BAT function rather than in the adaptive response to cold. Based on these observations, methods of increasing thermogenesis in a subject by administering a therapeutically effective amount of one or more agents that increase ERR? activity are provided.
Type:
Application
Filed:
March 21, 2018
Publication date:
July 26, 2018
Applicant:
Salk Institute for Biological Studies
Inventors:
Ronald M. Evans, Michael Downes, Annette Atkins, Ruth T. Yu, Maryam Ahmadian
Abstract: Provided herein are methods of treating pancreatic ductal adenocarcinoma in a mammalian subject. In some examples, such methods include administering a therapeutically effective amount of a VDR agonist (such as calcipotriol and/or paricalcitol) and administering a therapeutically effective amount of one or more chemotherapeutic agents, wherein the one or more chemotherapeutic agents comprise gemcitabine, 5-fluorouracil, cisplatin, protein-bound paclitaxel, and a PD-1 monoclonal antibody and/or PDL-1 monoclonal antibody.
Type:
Application
Filed:
February 19, 2018
Publication date:
July 19, 2018
Applicant:
Salk Institute for Biological Studies
Inventors:
Mara Sherman, Michael Downes, Ronald M. Evans
Abstract: The method provides methods and compositions for treating metabolic disorders such as impaired glucose tolerance, elevated blood glucose, insulin resistance, dyslipidemia, obesity, and fatty liver.
Type:
Application
Filed:
February 26, 2018
Publication date:
July 19, 2018
Applicant:
Salk Institute for Biological Studies
Inventors:
Johan W. Jonker, Michael Downes, Ronald M. Evans, Jae Myoung Suh
Abstract: The present disclosure provides FGF1 mutant proteins, such as those having an N-terminal deletion, point mutation(s), or combinations thereof, which can reduce blood glucose in a mammal. Such mutant FGF1 proteins can be part of a chimeric protein that includes a ?-Klotho-binding protein, an FGFR1c-binding protein, a ?-Klotho-binding protein and a FGFR1c-binding protein, a C-terminal region from FGF19 or FGF21. In some examples, mutant FGF1 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.
Type:
Application
Filed:
March 2, 2018
Publication date:
July 12, 2018
Applicant:
Salk Institute for Biological Studies
Inventors:
Jae Myoung Suh, Michael Downes, Ronald M. Evans, Annette Atkins, Ruth T. Yu
Abstract: The finding that phosphatidylserine (PtdSer) exposure on the outer leaflet of virally transduced cells triggers their engulfment by resident immune cells is described. It is demonstrated that inhibition of phospholipid scramblase 1 (PLSCR1) activity prevents PtdSer externalization and enables prolonged protection of vector-transduced cells from phagocytosis. Methods of inhibiting a virus vector-induced inflammatory response in tissue, methods of prolonging virus vector encoded transgene expression, and methods of modulating an inflammatory response in tissue of a subject, by administering an inhibitor of PLSCR1 are described.