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Please note that we are a research service provider, not a pharmacy or clinic, so we are unable to see patients and do not offer diagnostic and treatment services for individuals.

Hereditary Macular Dystrophy

Hereditary Macular Dystrophy (HMD) involves a group of retinal disorders of genetic origin with a tendency for progressive bilateral degeneration of the macula, the central area of the retina responsible for sharp central vision. Protheragen is dedicated to supporting the development of novel diagnostics and therapeutics for hereditary macular dystrophies through our comprehensive research services.

Overview of Hereditary Macular Dystrophy

Hereditary Macular Dystrophy (HMD) refers to a collection of inherited retinal diseases which mainly affect the macula, that is, the region at the center of the retina responsible for high-acuity vision. These diseases are marked by the progressive loss of photoreceptor and retinal pigment epithelial (RPE) cell function, resulting in severe central vision impairment. HMD can present as Stargardt disease as well as Best disease and Sorsby fundus dystrophy, which is associated with specific heritable and characteristics.

Schematic representation of P-5 in preserving and maintaining normal macular function.

Fig.1 P-5 plays an important role in preserving and maintaining normal macular function. (Kaminska, K., et al., 2025)

Pathogenesis of Hereditary Macular Dystrophy

The pathogenesis of Hereditary Macular Dystrophy is multifactorial and includes genetic alterations that disturb the normal functioning of photoreceptors as well as the retinal pigment epithelium (RPE). Genetic mutations, including ABCA4 (linked to Stargardt disease), result in the excessive buildup of harmful cellular byproducts within photoreceptor cells as well as oxidative stress, leading to cell death. In Best disease, the BEST1 gene mutations also impact the RPE, leading to hydrops and macular degeneration. Likewise, TIMP3 mutations in Sorsby fundus dystrophy cause macular degeneration as a result of abnormal extracellular matrix timbering RPE atrophy. Such genetic insults initiate an array of pathological changes such as oxidative stress, inflammation, and photoreceptor apoptosis, which ultimately result in vision impairment.

Therapeutics Development for Hereditary Macular Dystrophy

Gene Therapy

Addressing the fundamental genetic flaws of HMD using gene therapy may yield favorable results. Viral vectors like adeno-associated viruses (AAVs) may be customized to transfer functional versions of genes such as ABCA4 and BEST1 to the relevant cells. A prime example is the Stargardt disease where preclinical models have shown the possibility of AAV mediated delivery of ABCA4 gene to restore normal functioning of photoreceptors and cessation of degeneration. Direct alteration of the detrimental mutations using new technologies like CRISPR/Cas9 is also under consideration.

Cell Therapy

Cell therapy consists of transplanting healthy cells to replace damaged photoreceptors or RPE cells. Retinal human iPSCs can be differentiated into functional photoreceptors or RPE cells and can be transplanted into the subretinal area. Preclinical investigations have shown the survival and integration of transplanted cells, with some models exhibiting enhanced retinal functionality. For instance, in a rodent model of retinal degeneration, the subretinal transplantation of iPSC-derived RPE cells resulted in remarkable preservation of both functional photoreceptors and vision.

Small Molecule Drugs

Compound vitamins C and E and other antioxidants are capable of modulating oxidative stress and shielding photoreceptors from impact. Corticosteroids and other anti-inflammatory agents are efficient for chronic inflammation in the retina. Moreover, preclinical models suggest promise for some drugs that enhance autophagy, the process of removing malfunctioning organelles from a cell, in decelerating disease advancement. For instance, a small molecule that activates autophagy has been shown to reduce lipofuscin accumulation in a cell model of Stargardt disease.

Our Services

Protheragen's expertise in genetic screening and sequencing enables precise identification of disease-causing mutations, providing a foundation for targeted therapeutic development. We utilize advanced functional assays and imaging techniques to model disease phenotypes and identify biomarkers for early diagnosis and monitoring. Our therapeutics development services include the development and testing of gene therapies, cell therapies, and small-molecule drugs, leveraging state-of-the-art technologies and models to evaluate efficacy and safety.

Diagnostics Development

Therapeutic Development

Disease Models

ABCA4 Knockout Mice
Timp3 Knock-in Mice
ELOVL4 Knock-in Mice
ABCA4 Mutant Dogs
RPE65 Mutant Dogs
RDH5 Mutant Cats
CLN7 Mutant Monkeys
BBS7 Mutant Monkeys

Preclinical Research

Protheragen's preclinical research services for Hereditary Macular Dystrophy are designed to accelerate the development of effective therapeutics. We specialize in the creation and validation of animal models that accurately reflect the genetic and pathological features of HMD. If you are interested in our services, please feel free to contact us.

Reference

Kaminska, Karolina, et al. "Bi-allelic variants in three genes encoding distinct subunits of the vesicular AP-5 complex cause hereditary macular dystrophy." The American Journal of Human Genetics 112.4 (2025): 808-828.