Genetic therapy of Xeroderma Pigmentosum: analysis of strategies and translation

Gonçalves-Maia, Maria; Magnaldo, Thierry

doi:10.1080/21678707.2017.1256770

Cited by 5 publications

(9 citation statements)

References 127 publications

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“…Gene therapy: Early clinical and genetic diagnosis is essential. Attempts to genetically correct XP cells by retrovirus‐mediated gene transfer have been successful and held promise for ex vivo cutaneous gene therapy of XP cells using retrovirus‐mediated transfer of the therapeutic (XP) genes 27,28 . Ideal recommended plan for the treatment of XP is shown in Table 6.…”

Section: Discussionmentioning

confidence: 99%

Xeroderma pigmentosum in Yemen

Khatri

2021

Int J Dermatology

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Background The incidence of xeroderma pigmentosum (XP) in Yemen seems to be quite high but there are no previous reports. Objective To study the clinicoepidemiologic aspect of XP in Yemen. Methods All 40 patients (24 male and 16 female patients from 32 families) treated and followed between 1997 and 2014 were subjected to detailed analysis with the help of a standardized protocol. The diagnosis was based on clinical features and histopathologic data, when needed. The diagnosis of tumors was confirmed by histopathologic examination in all cases. Results The median age of onset of initial manifestations was 9.5 months, and that of malignant lesions was 7 years. Parents of the patients were not affected, but history of consanguinity was recorded in 38. Initial lesions, such as dryness of the skin and freckles on the face, were noticed in all patients. In addition, erythema of the face with photosensitivity was observed in 21 patients. Premalignant and malignant skin lesions observed later were actinic keratosis in 15 patients, lentigo maligna in one, squamous cell carcinoma (SCC) in 10, and basosquamous carcinoma in one. Eyes were affected with SCC in seven and malignant melanoma (MM) in two patients. SCC of the lip developed in two patients and that of the tongue in one patient. Judicious use of acitretin in 12 patients showed good result. Conclusion XP in Yemen is characterized by a relatively high incidence, high percentage of consanguinity in parents of the patients, early onset of initial manifestations, malignant tumors, and severe ocular and oral lesions. Acitretin showed good result.

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Section: Discussionmentioning

confidence: 99%

Xeroderma pigmentosum in Yemen

Khatri

2021

Int J Dermatology

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“…To date, among the photosensitive molecules, the photofrin is not recommended for the treatment of XP patients because it induces excessive wound healing and consequential scarring [125]. Therefore, the topical application of 5-aminolevulinic acid (ALA)-a synthetic precursor of the protoporphyrin IX-is now indicated as the best approach.…”

Section: Phototherapy and Laser Resurfacingmentioning

confidence: 99%

“…Nevertheless, it implies the onset of adverse effects, such as inflammation, scarring, altered pigmentation and a prolonged healing period [125,130]. Therefore, the fractionated/pulsed lasers are today the preferred method.…”

Section: Phototherapy and Laser Resurfacingmentioning

confidence: 99%

“…Some classes of anti-cancer drugs have been considered for the treatment of XP patients as alternative to the surgical resection of skin tumours. Among these, the topical application of 5-Fluorouracil (5-FU) or Imiquimod has demonstrated to be the most efficient drug [125]. In particular, 5-FU has shown to exert its functions through the inhibition of deoxythymidine mono-phosphate (dTMP), a key component in the replication and transcription of DNA [138,139].…”

Section: Chemotherapeutic Drugsmentioning

confidence: 99%

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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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“…The authors are aware of no studies as yet to evaluate the therapeutic potential of antioxidants in the treatment of XP, although genetic strategies to ameliorate ROS generation are being considered [ 158 ].…”

Section: Xeroderma Pigmentosummentioning

confidence: 99%

Evidence of Oxidative Stress and Secondary Mitochondrial Dysfunction in Metabolic and Non-Metabolic Disorders

Stępień

Heaton

Rankin

et al. 2017

JCM

108

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Mitochondrial dysfunction and oxidative stress have been implicated in the pathogenesis of a number of diseases and conditions. Oxidative stress occurs once the antioxidant defenses of the body become overwhelmed and are no longer able to detoxify reactive oxygen species (ROS). The ROS can then go unchallenged and are able to cause oxidative damage to cellular lipids, DNA and proteins, which will eventually result in cellular and organ dysfunction. Although not always the primary cause of disease, mitochondrial dysfunction as a secondary consequence disease of pathophysiology can result in increased ROS generation together with an impairment in cellular energy status. Mitochondrial dysfunction may result from either free radical-induced oxidative damage or direct impairment by the toxic metabolites which accumulate in certain metabolic diseases. In view of the importance of cellular antioxidant status, a number of therapeutic strategies have been employed in disorders associated with oxidative stress with a view to neutralising the ROS and reactive nitrogen species implicated in disease pathophysiology. Although successful in some cases, these adjunct therapies have yet to be incorporated into the clinical management of patients. The purpose of this review is to highlight the emerging evidence of oxidative stress, secondary mitochondrial dysfunction and antioxidant treatment efficacy in metabolic and non-metabolic diseases in which there is a current interest in these parameters.

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Genetic therapy of Xeroderma Pigmentosum: analysis of strategies and translation

Cited by 5 publications

References 127 publications

Xeroderma pigmentosum in Yemen

Xeroderma pigmentosum in Yemen

Xeroderma Pigmentosum: General Aspects and Management

Evidence of Oxidative Stress and Secondary Mitochondrial Dysfunction in Metabolic and Non-Metabolic Disorders

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