Ocular Diseases
Inherited Retinal Dystrophies (IRDs) are a group of rare genetic diseases that cause progressive dysfunction or loss of photoreceptors in the retina. The onset, severity, and rate of progression vary depending on the specific mutation and the type of cells affected.
Retinitis Pigmentosa
Vision loss may begin at birth or develop later in life. To date, more than 300 genes have been associated with IRDs. Retinitis Pigmentosa (RP) is the most common form of IRD, affecting approximately 1 in 4,000 people worldwide. It is the leading cause of irreversible blindness in developed countries among individuals under 70 years of age.
RP has a highly heterogeneous genetic basis. Most cases are monogenic, with mutations identified in more than 80 different genes. These genes are crucial for the normal structure and function of photoreceptors, the cells in the retina that detect and respond to visual stimuli.
Mutations in any of these genes cause a gradual loss of photoreceptor cells. The disease often begins with night blindness, followed by progressive narrowing of the visual field (tunnel vision) and, in many cases, complete loss of vision over time.
| Inheritance of RP | Estimate prevalence worldwide | RP causative genes |
|---|---|---|
| Autosomal dominant (adRP) | 15 to 25% | 24 genes associated |
| Autosomal recessive (arRP) | 5 to 20% | 46 genes associated |
| X-linked recessive (xlRP) | 7 to 15% | 6 genes associated |
| Non-mendelian inheritance | No data available | Exceptional rare cases |
| Simple or isolated (sRP) | 40-50% | Non-consanguineous affected individuals |
CURRENT CARE LEAVES MANY RETINITIS PIGMENTOSA PATIENTS BEHIND
Diagnosis
Retinitis pigmentosa symptoms vary greatly in both severity and rate of progression, making it difficult to establish a single standard approach to diagnosis, counselling, and treatment for all patients.
Clinical diagnosis of RP involves comprehensive assessment that may include medical history, visual field testing, retinal imaging to evaluate photoreceptor function, and molecular genetic testing.
Treatment & Management
Retinitis pigmentosa is a highly variable disease, making treatment especially challenging and underscoring the need for new strategies.
At Miramoon Pharma, we focus on a neuroprotective approach: while current options cannot cure the disease, our goal is to slow down or stop the degeneration of photoreceptors.
By protecting these cells and keeping them viable for longer—independently of the mutated gene—we aim to give patients a critically extended therapeutic window, allowing them more time to benefit from future curative treatments.
Symptomatic treatment:
Currently, there is no standardized and effective therapy for the treatment of early-stage retinitis pigmentosa. There are some proposed treatments, although they are not specific and cannot cure RP.
Curative treatment:
There is currently only one curative drug on the market for RP based on gene therapy. This treatment is only applicable to less than 1% of RP patients. Despite the promising potential of gene therapy to treat RP, this strategy has several limitations. Despite the promising potential of gene therapy to treat RP, this strategy has several limitations.
Targeting central pathogenic mechanisms represents a promising strategy to prevent disease progression of degenerative disorders that currently have no effective treatments.
The Disease Process
Multiple genes regulate photoreceptor activity by controlling the expression of proteins and channels, one of whose most critical functions is maintaining intracellular calcium levels, essential for transmitting visual signals.
Mutations in these genes disrupt calcium homeostasis, leading to photoreceptor damage and, ultimately, the degeneration of rods and cones.
Because calcium imbalance is a common hallmark of many forms of retinitis pigmentosa (RP), restoring proper calcium regulation in photoreceptors represents a promising therapeutic strategy.
Mutations in these genes disrupt calcium homeostasis, leading to photoreceptor damage and, ultimately, the degeneration of rods and cones.
Because calcium imbalance is a common hallmark of many forms of retinitis pigmentosa (RP), restoring proper calcium regulation in photoreceptors represents a promising therapeutic strategy.
RyR2 as a New Therapeutic Target for RP
Ryanodine receptor (RyR2) channels are essential for maintaining calcium balance in photoreceptors, which is crucial for their survival.
In models of inherited retinal diseases, changes in RyR2 activity contribute to cell stress and photoreceptor degeneration.
Our preclinical studies in mice show that normalizing RyR2 function can reduce cell stress and prevent photoreceptor death, highlighting it as a potential therapeutic target.