Stargardt disease is an inherited retinal condition caused by mutations in several genes; symptoms generally manifest themselves during childhood or adolescence.

Ascidian Therapeutics’ lead program targets ABCA4-associated retinopathies, such as Stargardt disease. IND-enabling studies are underway and this clinical development pathway is progressing toward clinical completion.

MCO-010

MCO-010 (sonpiretigene isteparvovec, suspension for intravitreal injection) is an ambient-light activatable multi-characteristic optogenetic monotherapy designed to target abundant inner retinal neurons to restore permanently lost vision in advanced Stargardt disease. Utilizing an AAV2 vector carrying an expression cassette capable of stimulating robust bipolar cell responses after intravitreal administration. Recently, MCO secured EUR61 Million Series A financing in order to develop this therapeutic.

MCO-010’s clinical program currently involves two trials; an open-label Phase 1 dose-ranging/escalation study and a randomized phase 2b multicenter, double-masked placebo-controlled trial in patients with advanced RP. Both of these studies aim to assess its safety and efficacy before ultimately leading to the submission of its Biologics License Application (BLA).

Nanoscope Therapeutics is a clinical-stage biotechnology company offering gene therapies to treat retinal diseases in working-age populations, specifically Stargardt disease and Retinitis Pigmentosa – two leading causes of blindness among these groups. Their lead asset MCO-010, an ambient-light activatable multi-characteristic optogenetic monotherapy being developed as their lead asset is set out to restore vision in people suffering from Stargardt disease and Retinitis Pigmentosa respectively – two leading causes of blindness among this age cohort.

MCO-010 demonstrated significant benefits in its phase 1/2 RESTORE trial, including increased visual acuity for patients in bifocal mode as well as improvements to central and lateral macular function and color-contrast sensitivity, increased number of ETDRS letters read with wearable magnifiers, as well as significant reduction in wearable magnifier-related side effects. Furthermore, phase 2b RESTORE trial demonstrated favorable safety profiles among MCO-010-treated patients.

The RESTORE trial will assess MCO-010’s effects on several secondary endpoints, such as functional vision and glare tolerance. Furthermore, it will investigate whether treatment enhances central and lateral macular function measures like spatial acuity, depth perception, contrast sensitivity. Enrollment should conclude in 2022 and results will be reported back by 2023.

This rapid synthesis was undertaken as part of an ongoing systematic review to explore interventions designed to slow the progression of autosomal recessive Stargardt macular dystrophy/retinitis pigmentosa (ARMD/RP). To do this, an established framework was employed by authors in selecting and assessing available evidence from multiple databases.

MCO-020

Researchers recently published in Nature their finding that oral gildeuretinol stopped progression of Stargardt disease in early-stage patients. It’s an important finding, because it shows oral treatments can slow vision loss caused by this condition over time. Furthermore, their team used an enzyme to break down bile acids in the eye which helped decrease levels of lipofuscin – a substance known as lipofuscin that builds up in retina and leads to progressive vision loss over time. This research project involved multiple groups including National Institutes of Health and the University of Colorado as part of collaboration efforts on multiple studies involving multiple groups such as this project.

Dr. Allen C. Ho, a professor at the University of Washington and member of Retina Society. It was a phase 1/2 open-label dose-ranging/dose escalation study involving 42 Stargardt disease subjects across five clinical trial centers in the US to test AAV5-hRORA to deliver an adeno-associated virus vector into their eye – targeting retinal pigment epithelium – an essential cell type essential to vision. Researchers discovered hRORA played key roles in multiple key pathways involving lipid metabolism, oxidative stress responses as well as anti-inflammatory responses.

Other studies have also demonstrated that Stargardt disease medications can improve vision in those suffering from it, with some trials being randomized controlled while others examining natural history data. One such natural history study of autosomal recessive Stargardt macular dystrophy in untreated eyes found that its central visual acuity (BCVA) gradually declined with age but at a slower pace than expected.

Proqr Therapeutics NV is developing gene therapies to treat Stargardt disease and other forms of macular degeneration, specifically QR-1011 for treating genetic mutations that cause this disorder. This therapy targets ABCA4 gene which produces protein essential to convert light into electrochemical signals for retina function; Proqr plans on publishing initial results of its STARLIGHT trial of this therapy by 2023.

RESTORE

Nanoscope Therapeutics of Dallas will present results of RESTORE, a clinical trial to test their multi-characteristic optineurin (MCO) gene therapy platform and therapeutic agent MCO-010 that targets Stargardt macular degeneration among others. They will also highlight recent progress made during Phase 2 multicenter open label trial STARLIGHT using MCO-010 with patients who have advanced Stargardt macular degeneration.

Nanoscope’s treatment involves injecting autologous bone marrow stem cells directly into the eye, where they regenerate damaged photoreceptors in the retina. A small study of 34 Stargardt disease patients saw either stabilization or improvement in vision; retinal prosthetics and anti-VEGF drugs can slow progression, but cannot restore lost vision. Nanoscope was one of two TechFW incubator clients to secure Orphan drug designation this week; AyuVis was also granted one for their pulmonary medicine being developed.

STARLIGHT

Starlight Cardiovascular’s treatment for Stargardt disease, or juvenile macular degeneration, uses an AAV vector to deliver gene-modified proteins directly into the eye’s transport process so it can convert light into electrochemical signals again. The company successfully completed a Phase 1/2 clinical trial that demonstrated both safety and efficacy of its approach for treating patients with genetically confirmed Stargardt disease with favorable clinical profiles, showing no adverse events related to systemic or ocular inflammation during this phase of testing. Average best corrected visual acuity improved by five ETDRS letters at both baseline and longitudinal locations with or without wearable magnifiers; Octopus visual field perimetry and multi-luminance shape discrimination testing also saw improvements at both points.

Starlight pays its respects to renowned cardiac surgeon Dr Nina Starr Braunwald, known for her passionate advocacy on behalf of children and families. Her legacy will continue to live on through Starlight’s efforts in inspiring and empowering young people everywhere.