Therapeutics of xeroderma pigmentosum: A PRISMA-compliant systematic review

Andrade, Fernando Antônio Gomes de; Cavalcanti, Cláudio Eduardo de Oliveira; Isoldi, Felipe Contoli; Ferreira, Lydia Masako

doi:10.25259/ijdvl_431_19

Cited by 8 publications

(11 citation statements)

References 63 publications

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“…If this pathway is defective, this predisposes to cancer. Only very few therapeutic possibilities are available for these diseases (de Andrade et al, 2021) (Weon and Glass, 2019). Screening of a library comprising Food and Drug Administration (FDA)-approved drugs has shown that the sulfonylureas acetohexamide and glimepiride are able in vitro to enhance viability in XPA cells after UV radiation at rather high dosages (Mazouzi et al, 2017).…”

Section: Interfering With the Pathophysiological Pathways Disturbed By The Mutated Gene Intervening In Disease Pathwaysmentioning

confidence: 99%

“…The most essential action of MSCs is likely the secretion of anti-inflammatory agents, whereas they may also differentiate into fibroblasts and keratinocytes. Transplanted patients are able to receive skin grafts from the same donor, which survive for long periods and outgrow into adjacent wounds, thereby suggesting immune tolerance and outgrowth of stem cells ( Ebens et al, 2020 ).…”

Section: Restoring the Underlying Gene Defect/productmentioning

confidence: 99%

“…While treatment modalities are still limited, some of them evolve rapidly in regard to secondary inflammatory or oncologic consequences. At this moment, treatment options are for most of these diseases restricted to skin and wound care, comprising compounded topical preparations, surgery, symptomatic pain relief, treatment of itching, as well as treatment of complications (Bardhan et al, 2020;Bodemer et al, 2021;Lenders and Brand, 2021) like skin cancers (de Andrade et al, 2021). This is complemented with patient education designed to enhance disease understanding and therapy adherence, as well as to teach how to avoid triggering factors, including heat and sun exposure among others (de Andrade et al, 2021;Dufresne et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…At this moment, treatment options are for most of these diseases restricted to skin and wound care, comprising compounded topical preparations, surgery, symptomatic pain relief, treatment of itching, as well as treatment of complications (Bardhan et al, 2020;Bodemer et al, 2021;Lenders and Brand, 2021) like skin cancers (de Andrade et al, 2021). This is complemented with patient education designed to enhance disease understanding and therapy adherence, as well as to teach how to avoid triggering factors, including heat and sun exposure among others (de Andrade et al, 2021;Dufresne et al, 2013). Only very few systemic drugs are available and if so, undesirable effects must be taken into account, given that treatment may be required from birth or an early age on, as in the case of retinoid administration.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Interfering With the Pathophysiological Pathways Disturbed By The Mutated Gene Intervening In Disease Pathwaysmentioning

confidence: 99%

Section: Restoring the Underlying Gene Defect/productmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Challenges in Treating Genodermatoses: New Therapies at the Horizon

Morren

Legius

Giuliano³

et al. 2022

Front. Pharmacol.

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“…Despite this, no evidence against the use of T4N5 liposomal formulations have been reported. In particular, acute and chronic safety tests have been performed in both mice and humans, demonstrating that no adverse reactions or significant alterations in skin biology are induced by Dimericine [84,194].…”

Section: Liposomal Formulations As Nanocarriers For Dna Repair Enzymesmentioning

confidence: 99%

Xeroderma Pigmentosum: General Aspects and Management

Piccione

Fortina

Ferri³

et al. 2021

JPM

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Xeroderma Pigmentosum (XP) is a rare genetic syndrome with a defective DNA nucleotide excision repair. It is characterized by (i) an extreme sensitivity to ultraviolet (UV)-induced damages in the skin and eyes; (ii) high risk to develop multiple skin tumours; and (iii) neurologic alterations in the most severe form. To date, the management of XP patients consists of (i) early diagnosis; (ii) a long-life protection from ultraviolet radiation, including avoidance of unnecessary UV exposure, wearing UV blocking clothing, and use of topical sunscreens; and (iii) surgical resections of skin cancers. No curative treatment is available at present. Thus, in the last decade, in order to prevent or delay the progression of the clinical signs of XP, numerous strategies have been proposed and tested, in some cases, with adverse effects. The present review provides an overview of the molecular mechanisms featuring the development of XP and highlights both advantages and disadvantages of the clinical approaches developed throughout the years. The intention of the authors is to sensitize scientists to the crucial aspects of the pathology that could be differently targeted. In this context, the exploration of the process underlining the conception of liposomal nanocarriers is reported to focus the attention on the potentialities of liposomal technology to optimize the administration of chemoprotective agents in XP patients.

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