Dry age-related macular degeneration: A currently unmet clinical need

Girmens, Jean-François; Sahel, José‐Alain; Marazova, Katia

doi:10.5582/irdr.2012.v1.3.103

Cited by 25 publications

(25 citation statements)

References 76 publications

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“…Interestingly, SOD2 knockdown in the RPE induces early AMD phenotypes (70), and many additional lines of evidence suggest that oxidation plays a role in AMD. These vectors may thus be useful in this disease, particularly for dry AMD, which has no effective treatment and is quite common in individuals over the age of 75 (71). The antioxidant gene therapy demonstrated here can significantly slow down cone death such that, in the fastest model of degeneration, the rd1 mouse, there are more cones present in the NRF2-treated retinae than in the GFP-treated retinae at P70.…”

Section: Discussionmentioning

confidence: 90%

NRF2 promotes neuronal survival in neurodegeneration and acute nerve damage

et al. 2015

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Section: Discussionmentioning

confidence: 90%

NRF2 promotes neuronal survival in neurodegeneration and acute nerve damage

et al. 2015

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“…Worldwide, there are more than 5 million people with GA (Sunness et al, 1997;Wong et al, 2014). Despite the increasing prevalence of GA, it currently remains a largely unmet clinical need as no approved therapy is available (Girmens et al, 2012). The pathogenesis of AMD is not well understood; however, genetic and environmental factors appear to contribute to the disease process (de Jong, 2006).…”

Section: Introductionmentioning

confidence: 99%

A Mechanistic Pharmacokinetic/Pharmacodynamic Model of Factor D Inhibition in Cynomolgus Monkeys by Lampalizumab for the Treatment of Geographic Atrophy

Le¹,

Gibiansky²,

Good³

et al. 2015

J Pharmacol Exp Ther

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Lampalizumab is an antigen-binding fragment of a humanized monoclonal antibody against complement factor D (CFD), a ratelimiting enzyme in the activation and amplification of the alternative complement pathway (ACP), which is in phase III clinical trials for the treatment of geographic atrophy. Understanding of the pharmacokinetics, pharmacodynamics, and biodistribution of lampalizumab following intravitreal administration in the ocular compartments and systemic circulation is limited but crucial for selecting doses that provide optimal efficacy and safety. Here, we sought to construct a semimechanistic and integrated ocularsystemic pharmacokinetic-pharmacodynamic model of lampalizumab in the cynomolgus monkey to provide a quantitative understanding of the ocular and systemic disposition of lampalizumab and CFD inhibition. The model takes into account targetmediated drug disposition, target turnover, and drug distribution across ocular tissues and systemic circulation. Following intravitreal administration, lampalizumab achieves rapid equilibration across ocular tissues. Lampalizumab ocular elimination is relatively slow, with a t 1/2 of approximately 3 days, whereas systemic elimination is rapid, with a t 1/2 of 0.8 hours. Target-independent linear clearance is predominant in the eye, whereas targetmediated clearance is predominant in the systemic circulation. Systemic CFD synthesis was estimated to be high (7.8 mg/day); however, the amount of CFD entering the eye due to influx from the systemic circulation was small (,10%) compared with the lampalizumab dose and is thus expected to have an insignificant impact on the clinical dose-regimen decision. Our findings support the clinical use of intravitreal lampalizumab to achieve significant ocular ACP inhibition while maintaining low systemic exposure and minimal systemic ACP inhibition.

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“…Age-related macular degeneration (AMD) is an acquired degeneration of the retina that causes significant central visual impairment [1,2]. AMD is the most common cause of irreversible vision loss in the developed world.…”

Section: Introductionmentioning

confidence: 99%

“…AMD is the most common cause of irreversible vision loss in the developed world. The disease manifests with two types: the non-neovascular or dry type, which includes the formation of drusen and retinal pigment epithelium abnormalities, and or wet type, which includes a choroidal neovascular membrane formation [1][2][3]. Approximately 85% to 90% of the cases of macular degeneration are dry type.…”

Section: Introductionmentioning

confidence: 99%

Fundus autofluorescence and multicolour imaging comparison in assessing disease severity in patients suffering from geographic atrophy. A case series analysis

Mallias

Mylova²,

Tassiopoulou³

2017

Ophthalmology J

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introduCtion. The aim of the study is to determine which depicting modality, fundus autofluorescence or multicolour imaging, is a better diagnostic tool in the monitoring of the progression of geographic atrophy in patients with severe dry macular degeneration. MateriaL and Methods. Fifty patients (93 eyes) participated in this study. OCT examination (Spectralis HRA + OCT, Heidelberg Engineering, Germany) was performed in order to confirm that they fit the criteria to proceed in the study. In all patients, fundus autofluorescence and multicolour imaging was performed. resuLts. The area of geographic atrophy was depicted with both modalities and useful information was obtained. In some cases, multicolour imaging provided more useful clues and in other cases the fundus autofluorescence provided useful information for the progression of the disease. ConCLusions. Both modalities provide a wide range of useful information about the progression of geographic atrophy in patients with severe dry age-related macular degeneration and should both be performed in order to gather all the useful information about the disease progression.

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Dry age-related macular degeneration: A currently unmet clinical need

Cited by 25 publications

References 76 publications

NRF2 promotes neuronal survival in neurodegeneration and acute nerve damage

NRF2 promotes neuronal survival in neurodegeneration and acute nerve damage

A Mechanistic Pharmacokinetic/Pharmacodynamic Model of Factor D Inhibition in Cynomolgus Monkeys by Lampalizumab for the Treatment of Geographic Atrophy

Fundus autofluorescence and multicolour imaging comparison in assessing disease severity in patients suffering from geographic atrophy. A case series analysis

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