Current and emerging treatments for albinism

Liu, Siyin; Kuht, Helen J; Moon, Emily Haejoon; Maconachie, Gail; Thomas, Mervyn G

doi:10.1016/j.survophthal.2020.10.007

Cited by 26 publications

(27 citation statements)

References 158 publications

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“…In addition, reaching an accurate diagnosis is especially important for informed genetic counselling and family planning advice, given the different inheritance patterns related to the other disease phenocopies. There are emerging gene-based applications for treating albinism [24] such as adeno-associated virus (AAV)-based Oa1 gene therapy which has been demonstrated in knockout mice models for ocular albinism [25] and with Tyr oculocutaneous albinism type 1 [26]. Successful CRISPR/Cas9 gene editing of Tyr has also been demonstrated for albinism in rabbits [27].…”

Section: Discussionmentioning

confidence: 99%

Novel Biallelic Variants and Phenotypic Features in Patients with SLC38A8-Related Foveal Hypoplasia

Schiff

Tailor

Chan

et al. 2021

IJMS

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Biallelic pathogenic variants in solute carrier family 38 member 8, SLC38A8, cause a pan-ocular autosomal recessive condition known as foveal hypoplasia 2, FVH2, characterised by foveal hypoplasia, nystagmus and optic nerve chiasmal misrouting. Patients are often clinically diagnosed with ocular albinism, but foveal hypoplasia can occur in several other ocular disorders. Here we describe nine patients from seven families who had molecularly confirmed biallelic recessive variants in SLC38A8 identified through whole genome sequencing or targeted gene panel testing. We identified four novel sequence variants (p.(Tyr88*), p.(Trp145*), p.(Glu233Gly) and c.632+1G>A). All patients presented with foveal hypoplasia, nystagmus and reduced visual acuity; however, one patient did not exhibit any signs of chiasmal misrouting, and three patients had features of anterior segment dysgenesis. We highlight these findings in the context of 30 other families reported to date. This study reinforces the importance of obtaining a molecular diagnosis in patients whose phenotype overlap with other inherited ocular conditions, in order to support genetic counselling, clinical prognosis and family planning. We expand the spectrum of SLC38A8 mutations which will be relevant for treatment through future genetic-based therapies.

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Section: Discussionmentioning

confidence: 99%

Novel Biallelic Variants and Phenotypic Features in Patients with SLC38A8-Related Foveal Hypoplasia

Schiff

Tailor

Chan

et al. 2021

IJMS

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“…Melaninin pigmentasyondan (cilt, saç ve göz rengi) sorumlu olmasının yanı sıra ultraviyole (UV) ışığının zararlı etkilerine karşı bariyer görevi vardır. [10][11][12] Melanin pigmentinin eksikliği UV ışınlarına karşı hassasiyete sebebiyet verir. Cilt pigmentasyonunun derecesi, güneş kaynaklı cilt kanseri riski ile ters orantılıdır.…”

Section: Patogenezunclassified

“…İridosikliti olan hastalarda ön kamarada ve vitreusta hücre, korneada keratik presipitatlar, anterior ve posterior sineşi, konjonktival hiperemi, göz içi basıncında değişiklikler gibi eşlik eden bulgular vardır. [12] Herpetik iridosiklitlerde de iriste sektöryel atrofiler ve göz içi basıncında yükselmeler eşlik edebilir. Fuchs üveitinde de iriste transillimünasyon beklenir ama genellikle tek taraflı olması ve ön kamara hücresinin eşlik etmesi ayırıcı özelliğidir.…”

Section: Tanıunclassified

“…Hafif olgular hariç hemen hemen tamamında foveal hipoplazi görülmektedir. [12] Fovea, retinanın ayrıntılı görme yeteneğine sahip tek kısmıdır. Her ne kadar aksamış fovea gelişimi albinizmde klasik bir bulgu olarak kabul edilse de, hem klinik hem de görüntüleme çalışmaları ilkel foveal gelişimi olan bazı bireyleri tanımlamıştır, bu da foveal hipoplazinin (veya fovea plana) tüm bireylerde maküler anatomiyi tanımlamak için yeterli olmayabileceğini göstermektedir.…”

Section: Tanıunclassified

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Ocular and Oculocutaneous Albinism: Pathogenesis, Diagnosis, and Treatment

2023

Güncel Retina (Current Retina)

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Oculocutaneous albinism (OCA) is the common name of a group of hereditary diseases accompanied by disorders in the production of melanin pigment and affect the hair, skin, and eyes. Besides being responsible for pigmentation, melanin acts as a barrier against the harmful effects of ultraviolet (UV) light. Individuals with pigment deficiency are at risk for the development of disorders such as visual impairment and nystagmus, as well as the development of skin cancer depending on the type of disease and therefore the degree of pigmentation. The diagnosis of OCA is mainly based on dermatological and biomicroscopic examination. Although there is no specific treatment method for ocular or oculocutaneous albinism today, treatments to improve patients' quality of life and protective measures are important.

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“…Upon Cas binding, hybridization of the guide RNA spacer to the target DNA strand causes displacement of the PAM-containing genomic DNA strand to form a ssDNA R-loop ( Anzalone et al, 2020 ), while within this loop, bases can be edited. A first proof of concept study was conducted in RDEB, providing promising results ( Osborn et al, 2020 ). The technique’s advantage is that it is template independent, giving rise to fewer indels, while enabling high correction efficacy.…”

Section: Restoring the Underlying Gene Defect/productmentioning

confidence: 99%

Challenges in Treating Genodermatoses: New Therapies at the Horizon

Morren

Legius

Giuliano³

et al. 2022

Front. Pharmacol.

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Genodermatoses are rare inherited skin diseases that frequently affect other organs. They often have marked effects on wellbeing and may cause early death. Progress in molecular genetics and translational research has unravelled many underlying pathological mechanisms, and in several disorders with high unmet need, has opened the way for the introduction of innovative treatments. One approach is to intervene where cell-signaling pathways are dysregulated, in the case of overactive pathways by the use of selective inhibitors, or when the activity of an essential factor is decreased by augmenting a molecular component to correct disequilibrium in the pathway. Where inflammatory reactions have been induced by a genetically altered protein, another possible approach is to suppress the inflammation directly. Depending on the nature of the genodermatosis, the implicated protein or even on the particular mutation, to correct the consequences or the genetic defect, may require a highly personalised stratagem. Repurposed drugs, can be used to bring about a “read through” strategy especially where the genetic defect induces premature termination codons. Sometimes the defective protein can be replaced by a normal functioning one. Cell therapies with allogeneic normal keratinocytes or fibroblasts may restore the integrity of diseased skin and allogeneic bone marrow or mesenchymal cells may additionally rescue other affected organs. Genetic engineering is expanding rapidly. The insertion of a normal functioning gene into cells of the recipient is since long explored. More recently, genome editing, allows reframing, insertion or deletion of exons or disruption of aberrantly functioning genes. There are now several examples where these stratagems are being explored in the (pre)clinical phase of therapeutic trial programmes. Another stratagem, designed to reduce the severity of a given disease involves the use of RNAi to attenuate expression of a harmful protein by decreasing abundance of the cognate transcript. Most of these strategies are short-lasting and will thus require intermittent life-long administration. In contrast, insertion of healthy copies of the relevant gene or editing the disease locus in the genome to correct harmful mutations in stem cells is more likely to induce a permanent cure. Here we discuss the potential advantages and drawbacks of applying these technologies in patients with these genetic conditions. Given the severity of many genodermatoses, prevention of transmission to future generations remains an important goal including offering reproductive choices, such as preimplantation genetic testing, which can allow selection of an unaffected embryo for transfer to the uterus.

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Current and emerging treatments for albinism

Cited by 26 publications

References 158 publications

Novel Biallelic Variants and Phenotypic Features in Patients with SLC38A8-Related Foveal Hypoplasia

Novel Biallelic Variants and Phenotypic Features in Patients with SLC38A8-Related Foveal Hypoplasia

Ocular and Oculocutaneous Albinism: Pathogenesis, Diagnosis, and Treatment

Challenges in Treating Genodermatoses: New Therapies at the Horizon

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