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A combination treatment based on drug repurposing demonstrates mutation agnostic efficacy in pre-clinical retinopathy models.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE238218 | GEO | 2024/06/06

REPOSITORIES: GEO

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A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models.

Project description:Inherited retinopathies are devastating diseases that in most cases lack treatment options. Disease-modifying therapies that mitigate pathophysiology regardless of the underlying genetic lesion are desirable due to the diversity of mutations found in such diseases. We tested a systems pharmacology-based strategy that suppresses intracellular cAMP and Ca2+ activity via G protein-coupled receptor (GPCR) modulation using tamsulosin, metoprolol, and bromocriptine coadministration. The treatment improves cone photoreceptor function and slows degeneration in Pde6βrd10 and RhoP23H/WT retinitis pigmentosa mice. Cone degeneration is modestly mitigated after a 7-month-long drug infusion in PDE6A-/- dogs. The treatment also improves rod pathway function in an Rpe65-/- mouse model of Leber congenital amaurosis but does not protect from cone degeneration. RNA-sequencing analyses indicate improved metabolic function in drug-treated Rpe65-/- and rd10 mice. Our data show that catecholaminergic GPCR drug combinations that modify second messenger levels via multiple receptor actions provide a potential disease-modifying therapy against retinal degeneration.

| S-EPMC11251169 | biostudies-literature

A combination treatment based on drug repurposing demonstrates mutation agnostic efficacy in pre-clinical retinopathy models. [RNA-seq: Rd10]

Project description:To determine the gene expression changes in the retina of two separate groups (experimental groups: vehicle and TMB) of vivarium-reared 5-week-old Rd10 mice (strong disease), as well as one group of 4-week-old dark-reared Rd10 mice (mild disease) and one group of wild-type mice (healthy). TMB group received dietary administration of tamsulosin, metoprolol and bromocriptine drug cocktail between 4-5-weeks of age, for 9 days prior to sample collection. All other groups received base/vehicle diet.

2024-06-06 | GSE238217 | GEO

A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models [scRNA-seq: Rd10]

Project description:To determine the gene expression changes in the retina of 2-month-old Rd10 mice reared in darkness throughout their lifespan, we collected retina samples from Rd10 and WT (C57BL/6J mice) mice, generated single-cell suspensions, and performed scRNA-Seq (10X Genomics). One group of Rd10 mice was treated for 1 month via dietary administration of tamsulosin, metoprolol and bromocriptine drug cocktail.

2024-06-06 | GSE234797 | GEO

A combination treatment based on drug repurposing demonstrates mutation agnostic efficacy in pre-clinical retinopathy models. [RNA-seq: RPE65-KO]

Project description:To determine the gene expression changes in the retina of two separate groups (experimental groups: vehicle and TMB) of Rpe65-/- mice at P64, as well as one group of age-matched wild-type mice (healthy). Mice in the TMB group received dietary administration of tamsulosin, metoprolol and bromocriptine drug cocktail between P22-P64. All other mice received base/vehicle diet.

2024-06-06 | GSE238216 | GEO

A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models [scRNA-seq: Rpe65-KO]

Project description:To determine the gene expression changes in the retina P57-P60 Rpe65-/- mice , we collected retina samples from Rpe65-/- and WT (C57BL/6J mice) mice, generated single-cell suspensions, and performed scRNA-Seq (10X Genomics). One group of Rpe65-/- mice was treated for 5 weeks via dietary administration of tamsulosin, metoprolol and bromocriptine drug (TMB) cocktail.

2024-06-06 | GSE263877 | GEO

A combination treatment based on drug repurposing demonstrates mutation agnostic efficacy in pre-clinical retinopathy models.

Project description:A combination treatment based on drug repurposing demonstrates mutation agnostic efficacy in pre-clinical retinopathy models.

| PRJNA998379 | ENA

A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models [scRNA-seq: Rd10]

Project description:A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models [scRNA-seq: Rd10]

| PRJNA983249 | ENA

A combination treatment based on drug repurposing demonstrates mutation agnostic efficacy in pre-clinical retinopathy models. [RNA-seq: Rd10]

Project description:A combination treatment based on drug repurposing demonstrates mutation agnostic efficacy in pre-clinical retinopathy models. [RNA-seq: Rd10]

| PRJNA998385 | ENA

A combination treatment based on drug repurposing demonstrates mutation agnostic efficacy in pre-clinical retinopathy models. [RNA-seq: RPE65-KO]

Project description:A combination treatment based on drug repurposing demonstrates mutation agnostic efficacy in pre-clinical retinopathy models. [RNA-seq: RPE65-KO]

| PRJNA998380 | ENA

A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models [scRNA-seq: Rpe65-KO]

Project description:A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models [scRNA-seq: Rpe65-KO]

| PRJNA1099665 | ENA

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