Last update 01 Nov 2024

RLBP1

Last update 01 Nov 2024

Basic Info

Synonyms

Cellular retinaldehyde-binding protein, CRALBP, retinaldehyde binding protein 1

+ [2]

Introduction

Soluble retinoid carrier essential the proper function of both rod and cone photoreceptors. Participates in the regeneration of active 11-cis-retinol and 11-cis-retinaldehyde, from the inactive 11-trans products of the rhodopsin photocycle and in the de novo synthesis of these retinoids from 11-trans metabolic precursors. The cycling of retinoids between photoreceptor and adjacent pigment epithelium cells is known as the 'visual cycle'.

Drugs associated with RLBP1

CPK-850

Target

RLBP1

Mechanism

RLBP1 stimulants

Active Org.

Novartis Pharmaceuticals Corp.

Originator Org.

Novartis Pharma AG

Active Indication

Retinitis Pigmentosa

Inactive Indication-

Drug Highest PhasePhase 1/2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

HORA RLBP1

Target

RLBP1

Mechanism

RLBP1 stimulants

Active Org.

Coave TherapeuticsStartup

Originator Org.

Atos SE [+1]

Active Indication

Retinitis Pigmentosa

Inactive Indication

Fundus Albipunctatus

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with RLBP1

NCT03374657 / Active, not recruitingPhase 1/2

An Open-label First-in-human Single Ascending Dose Study to Explore Safety, Tolerability and Efficacy of Subretinal Administration of CPK850 Gene Therapy in Patients With Retinitis Pigmentosa Due to Mutations in the Retinaldehyde Binding Protein 1 (RLBP1) Gene

The purpose of this first-in-human study is to explore the maximum tolerated dose (MTD) of CPK850 as determined by the single ascending dose ranging portion of the study. This study will also evaluate the safety and potential efficacy of CPK850 on improving visual function in patients with decreased visual function from RLBP1 retinitis pigmentosa due to biallelic mutations in the RLBP1 gene.

Start Date22 Aug 2018

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

100 Clinical Results associated with RLBP1

100 Translational Medicine associated with RLBP1

0 Patents (Medical) associated with RLBP1

375

Literatures (Medical) associated with RLBP1

01 Nov 2024·American Journal of Ophthalmology

RDH5 and RLBP1-Associated Inherited Retinal Diseases: Refining the Spectrum of Stationary and Progressive Phenotypes

Article

Author: Bianco, Lorenzo ; Condroyer, Christel ; Audo, Isabelle ; Navarro, Julien ; Zeitz, Christina ; Antropoli, Alessio ; Sahel, José-Alain ; Benadji, Amine ; Antonio, Aline

PURPOSETo investigate the clinical, functional, and imaging characteristics in patients affected by inherited retinal diseases associated with RDH5 and RLBP1 gene variants, and to report novel genotype-phenotype correlations.DESIGNRetrospective single-center cohort study.METHODSTwenty-two patients with molecularly confirmed RLBP1-associated retinopathy and 5 with RDH5-associated retinopathy. Medical records were reviewed to obtain data on family history and ophthalmologic examinations, including retinal imaging and full-field electroretinography (ffERG). Genotype was determined by targeted next-generation sequencing followed by confirmation and familial segregation by Sanger sequencing.RESULTSThe median (interquartile ranges) age at baseline for the RDH5 and RLBP1 cohort was 44.6 (38.2-67.9) years and 36.9 (23.1-45.2) years, respectively. Macular atrophy (MA) was found in approximately 80% of eyes from both cohorts. The RLBP1 genotype was associated with a lower macular volume by 0.28 mm³ (95% CI, -0.46 to -0.11; P = .005) compared to the RDH5 genotype. In both genotypic cohorts, we found a significant annual rate of macular volume loss, estimated at -0.007 mm³/y (95% CI, -0.012 to -0.001; P = .02), without any significant difference between the two genotypes. Three unrelated patients homozygous for the c.361C>T p.(Arg121Trp) RLBP1 variant showed minimal impairment of both the rod and cone systems function on ffERG and absence of MA.CONCLUSIONSProgressive MA in addition to congenital night blindness can be identified in adult patients with RDH5-associated retinopathy. Vice versa, hypomorphic RLBP1 variants may cause milder retinal phenotypes rather than the typical severe rod-cone dystrophy with MA. These findings could prove beneficial to improve the prognostication of patients and help in designing future interventional trials.

01 Oct 2024·Molecular Therapy

Dual CRALBP isoforms unveiled: iPSC-derived retinal modelling and AAV2/5-RLBP1 gene transfer raise considerations for effective therapy

Article

Author: Hirtz, Christopher ; Bernex, Florence ; Brabet, Philippe ; Redmond, T Michael ; Sanjurjo-Soriano, Carla ; Erkilic, Nejla ; Mamaeva, Daria ; Guillou, Laurent ; Dubois, Gregor ; Meunier, Isabelle ; Kalatzis, Vasiliki ; Bocquet, Béatrice ; Arsenijevic, Yvan ; Redmond, T. Michael ; Damodar, Krishna ; Boukhaddaoui, Hassan ; Pequignot, Marie ; Vialaret, Jérôme

Inherited retinal diseases (IRDs) are characterised by progressive vision loss. There are over 270 causative IRD genes and variants within the same gene can cause clinically distinct disorders. One example is RLBP1 that encodes CRALBP. CRALBP is an essential protein in the rod and cone visual cycles that take place primarily in the retinal pigment epithelium (RPE) but also in Müller cells of the neuroretina. RLBP1 variants lead to three clinical subtypes: Bothnia dystrophy, retinitis punctata albescens and Newfoundland rod-cone dystrophy. We modelled RLBP1-IRD subtypes using patient-specific iPSC-derived RPE and identified pathophysiological markers that served as pertinent therapeutic read-outs. We developed an AAV2/5-mediated gene supplementation strategy and performed a proof-of-concept study in the human models, which was validated in vivo in an Rlbp1^-/- murine model. Most importantly, we identified a previously unsuspected smaller CRALBP isoform that is naturally and differentially expressed both in the human and murine retina. This previously unidentified isoform is produced from an alternative methionine initiation site. This work provides further insights into CRALBP expression and RLBP1-associated pathophysiology and raises important considerations for successful gene supplementation therapy.

10 Sep 2024·Nature communications

Interim safety and efficacy of gene therapy for RLBP1-associated retinal dystrophy: a phase 1/2 trial.

Article

Author: Stasi, Kalliopi ; Liew, Melissa S H ; Jennings, Nicki ; Holopigian, Karen ; Geirsdottir, Asbjörg ; Watters, Christine ; Westman, Sofie ; Grosskreutz, Cynthia ; Venkataraman, Abinaya ; André, Helder ; Rangaswamy, Nalini ; Burstedt, Marie ; Bigelow, Chad ; Kvanta, Anders

Gene therapy holds promise for treatment of inherited retinal dystrophies, a group of rare genetic disorders characterized by severe loss of vision. Here, we report up to 3-year pre-specified interim safety and efficacy results of an open-label first-in-human dose-escalation phase 1/2 gene therapy clinical trial in 12 patients with retinal dystrophy caused by biallelic mutations in the retinaldehyde-binding protein 1 (RLBP1) gene of the visual cycle. The primary endpoints were systemic and ocular safety and recovery of dark adaptation. Secondary endpoints included microperimetry, visual field sensitivity, dominant eye test and patient-reported outcomes. Subretinal delivery of an adeno-associated viral vector (AAV8-RLBP1) was well tolerated with dose-dependent intraocular inflammation which responded to corticosteroid treatment, and focal atrophy of the retinal pigment epithelium as the dose limiting toxicity. Dark adaptation kinetics, the primary efficacy endpoint, improved significantly in all dose-cohorts. Treatment with AAV8-RLBP1 resulted in the resolution of disease-related retinal deposits, suggestive of successful restoration of the visual cycle. In conclusion, to date, AAV8-RLBP1 has shown preliminary safety and efficacy in patients with RLBP1-associated retinal dystrophy. Trial number: NCT03374657.

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