Researchers are taking several Stargardt disease treatments into clinical testing this year, such as RNA exon editors and antisense oligonucleotides.

Lipofuscin accumulates in retinal pigment epithelium cells as a result of gene mutations and contributes to progressive vision loss and the formation of drusen. As this waste product accumulates over time, vision loss progresses rapidly.

MCO-010

MCO-010 is an optogenetic monotherapy developed by Nanoscope Therapeutics – a clinical-stage biotechnology company. This therapy has been demonstrated to restore vision in mice. MCO-010 could potentially treat various retinal diseases including Stargardt disease and Retinitis Pigosa (RP). MCO-010 acts as an ambient-light activatable gene-based therapy targeting inner retinal neurons to elicit wide range functional responses that could ultimately restore vision permanently in advanced cases of RP patients.

Gene mutations responsible for Stargardt disease lead to the accumulation of lipofuscin – a toxic waste substance composed of lipids, proteins, and toxic bis retinoids – in retinal pigment epithelium cells over time. Over time this causes degeneration of vision as lipofuscin accumulates over time resulting in vision loss resulting in legal blindness. Legal blindness is often passed along genetically.

Nanoscope Therapeutics is dedicated to developing gene-agnostic, sight-restoring optogenetic therapies for millions of people worldwide affected by retinal degenerative diseases that lack current treatments. Their lead asset MCO-010 is currently being tested in Phase 2b multicenter, randomized double-masked sham controlled clinical trials for Retinitis Pigmentosa and Stargardt disease patients in the U.S.; additionally MCO-010 received Fast Track and Orphan Drug designation from FDA respectively for these trials.

University of Michigan Health System’s Ophthalmology Research Team recently published a paper exploring the effect of orally administered ALK-001 on Stargardt disease progression in a mouse model of this disorder. Results demonstrated that ALK-001 significantly reduced formation of drusen within retina and protected it against oxidative damage. Furthermore, researchers intend to further examine ALK-001 effects using other models of Stargardt and dry age-related macular degeneration.

ACDN-01

Proqr Therapeutics NV, one of several companies developing treatments for Stargardt disease, is testing an antisense oligonucleotide called QR-1011 which aims to correct splicing abnormalities in the ABCA4 gene that cause this disorder. The trial will include patients diagnosed either clinically or genetically as having Stargardt disease and will include multiple vision function tests including ETDRS 50 cm charts both with and without wearable magnifiers; Octopus visual field perimetry; and multi-luminance shape discrimination tests.

Gene therapy offers great promise for restoring vision lost from Stargardt disease. Atidarsagene autotemcel, one of the company’s lead candidates, has demonstrated on-target effects across multiple measurements while having a favorable safety profile; additionally it holds orphan drug designation in several indications, such as Stargardt disease and retinitis pigmentosa associated with Usher syndrome type 1b.

The gene therapy company AAVantgarde Bio SrL is raising a series A financing of EUR61 million ($65 million). They intend to use this money for two innovative AAV gene-delivery technologies that overcome packaging limitations of AAV vectors, and AAVantgarde’s lead program — using AAV gene-based therapy against mutations of ABCA4 gene — is expected to enter clinical testing later this year.

ALK-001 is a once-daily oral medication designed to prevent lipofuscin accumulation in retinal pigment epithelia. Lipofuscin is a metabolic waste product produced in our bodies which accumulates in non-dividing tissues like RPE. When these deposits appear in eyes they contribute to macular degeneration and drusen formation.

QR-1011

Stargardt disease treatments range from drug therapies and cell and gene therapies, such as gene editing, to cell therapies that improve retinal health and slow its degeneration. Some of the more promising approaches include gene therapy, RNA exon editing, optical coherence tomography (OCT) imaging technology. Furthermore, several firms are researching new formulations and delivery systems for eye drops; Aequus Pharmaceuticals and Revision Therapeutics recently collaborated to create REV-0100 to reduce lipofuscin accumulation while Aldeyra announced phase 3 TRANQUILITY results of its reproxalap treatment against dry AMD/Stargardt disease.

The ABCA4 gene provides instructions for producing a protein essential to visual processing by transporting retinaldehyde through retinal pigment epithelial cells. Certain sequence variants in this gene cause Stargardt disease, which involves accumulation of toxic waste product called lipofuscin in retinal pigment epithelial cells; this accumulates and leads to the appearance of drusen as well as eventual vision loss.

Proqr Therapeutics NV recently conducted a clinical trial to assess the efficacy of QR-1011. This antisense oligonucleotide targets abnormalities in ABCA4 gene that alter protein expression levels, marking its success as the first gene therapy treatment for Stargardt disease to enter clinical trial stages. 25 participants with genetically confirmed Stargardt disease who exhibited best corrected visual acuities between 1.3 logMAR and 1.9 logMAR were included; safety testing including early treatment diabetic retinopathy studies charts, Octopus visual field perimetry testing and multi luminance shape discrimination testing were all monitored throughout this research process.

AAVantgarde Bio SrL recently secured EUR61 million through a series A financing round to advance their optogenetic approach to gene therapy. Utilizing their technology, AAVantgarde hopes to overcome traditional AAV vector limitations which are restricted by how much genetic cargo they can transport; AAVantgarde plans on starting its first clinical program later this year for treating retinitis pigmentosa associated with Usher Syndrome type 1b patients.

Xipere

Xipere is a corticosteroid medication approved for treating stargardt disease. As the first approved treatment of its kind, it reduces inflammation in the eye while relieving macular edema. Thanks to its unique suprachoroidal delivery system, Xipere reaches retina and choroid fluid buildup that leads to blurry vision – an area often neglected when treatment options for stargardt are limited. Administered through Bausch And Lomb Inc, its active ingredient triamcinolone acetonide protects intellectual property rights as an injection into eye.

Stargardt disease is an inherited disorder caused by mutations to the ABCA4 gene. This condition results in subretinal deposition of lipofuscin-like substances, eventually leading to photoreceptor death and eventual blindness. Although several treatments for Stargardt exist – dietary supplements, lutein, zinc carnosine – Xipere is a unique alternative that addresses its root cause instead of just treating lost vision.

CMS (Centers for Medicare and Medicaid Services) recently issued a permanent J-code for Xipere medication to facilitate access for Medicare beneficiaries as well as reimbursement by commercial and government payers.

Patients diagnosed with Stargardt disease (STGD1) containing two or more ABCA4 mutations will find benefit in using Xipere treatment. This eye injection is intended to treat macular edema caused by noninfectious uveitis. Clinical studies have demonstrated its efficacy, and its suprachoroidal delivery method reduces side effects compared to traditional anterior segment use. More research needs to be conducted before this drug can be recommended routinely; further evaluation must take place first in order to understand risks and benefits, and manage medication accordingly.

Antisense oligonucleotides

Antisense oligonucleotides represent an emerging field in medicine that holds great promise for treating diseases at their genetic root. These synthetic short sequences of nucleotides bind directly to specific RNA targets and effectively silence genes; often used as primer and probe reagents in PCR and microarray-based diagnostic test kits and now being developed into direct therapeutic agents to treat various medical conditions.

Stargardt disease is caused by mutations to the ABCA4 gene, which provides instructions for producing a protein essential to vision processing in the retina. This protein transports retinaldehyde necessary for light conversion into electrochemical signals in the retina – but due to mutations, its function no longer functions normally and patients experience progressive loss of vision. There have been various clinical trials conducted attempting to treat Stargardt disease using antisense drugs and gene therapy, yet none has proven successful at doing so yet.

Companies are currently creating antisense oligonucleotides to target the ABCA4 gene responsible for Stargardt disease. These antisense molecules can reduce lipofuscin accumulation in animal models while blocking production of toxic protein aggregates that damage cells of retinal pigment epithelium cells and stimulate stem cell growth; additionally they can inhibit complement system dysregulation as well as stem cell growth stimulation in retinal pigment epithelium cells. Tinlarebant (LBS-008; Belite Bio) has proven safe and effective treatment results in children diagnosed with Stargardt disease. Its development and evaluation has already led to promising results in children. DRAGON Trial study results have demonstrated this potential and has already produced promising results in treating children affected by Stargardt disease – safe yet effective medication with limited side effects seen so far compared with treatment of harmful protein aggregate production as well as potential complement system dysregulation as well as stimulation of stem cell growth. Currently being evaluated under phase 3 study evaluation through its evaluation in children diagnosed with Stargardt disease. tinlarebant (LBS-008; belite Bio) is being evaluated in its phase 3 trial evaluation phase 3 study called the DRAGON trial currently, showing signs of being safe yet effective against Stargardt.