CLERAPLIQ

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Clerapliq – RGTA® mimic heparan sulfate in regenerative medicine

Clerapliq -RGTA® or ReGeneraTing Agents mimic heparan sulfate in regenerative medicine: from concept to curing patients

Denis Barritault & Marie Gilbert-Sirieix & Kim Lee Rice & Fernando Siñeriz & Dulce Papy-Garcia & Christophe Baudouin & Pascal Desgranges & Gilbert Zakine & Jean-Louis Saffar8 & Johan van Neck

Abstract The importance of extracellular matrix (ECM) in- tegrity in maintaining normal tissue function is highlighted by numerous pathologies and situations of acute and chronic in- jury associated with dysregulation or destruction of ECM components. Heparan sulfate (HS) is a key component of the ECM, where it fulfils important functions associated with tissue homeostasis. Its degradation following tissue injury dis- rupts this delicate equilibrium and may impair the wound healing process. ReGeneraTing Agents (RGTA®s) are poly- saccharides specifically designed to replace degraded HS in injured tissues. The unique properties of RGTA® (resistance to degradation, binding and protection of ECM structural and signaling proteins, like HS) permit the reconstruction of the ECM, restoring both structural and biochemical functions to this essential substrate, and facilitating the processes of tissue repair and regeneration. Here, we review 25 years of research surrounding this HS mimic, supporting the mode of action, pre-clinical studies and therapeutic efficacy of RGTA® in the clinic, and discuss the potential of RGTA® in new branches of regenerative medicine.

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Clerapliq – JAMA Ophtalmology

Clerapliq – Jama Ophtalmology clinical trial

2016 Oct 1;134(10):1169-1176.

doi: 10.1001/jamaophthalmol.2016.3019.

Ahmed M Bata , Katarzyna J Witkowska , Piotr A Wozniak , Klemens Fondi , Gerald Schmidinger , Niklas Pircher , Stephan Szegedi , Valentin Aranha Dos Santos , Anca Pantalon , René M Werkmeister, Gerhard Garhofer , Leopold Schmetterer, Doreen Schmidl

Importance: Corneal abrasions are frequent after standard (epithelium-off [epi-off]) corneal collagen cross-linking (CXL) in patients with progressive keratoconus. A new matrix therapy agent (ReGeneraTing Agent [RGTA]) has been developed to promote corneal wound healing.

Objective: To assess the effect of the new type of matrix therapy agent on corneal wound healing after epi-off CXL in patients with keratoconus.

Design, setting, and participants: This double-masked randomized clinical trial enrolled 40 patients with keratoconus undergoing epi-off CXL from July 18, 2014, to October 21, 2015, when the last follow-up was completed. The analysis of the intention-to-treat population was performed at the Department of Clinical Pharmacology in cooperation with the Center for Medical Physics and Biomedical Engineering and the Department of Ophthalmology and Optometry of the Medical University of Vienna.

Interventions: Patients were randomized to receive the matrix therapy agent or hyaluronic acid-containing eyedrops, 0.1%, every other day starting immediately after surgery. The size of the corneal defect was measured using ultrahigh-resolution optical coherence tomography (OCT) and slitlamp photography (SLP) with fluorescein staining.

Main outcomes and measures: Corneal wound healing rate, defined as the size of the defect over time.

Results: Among the 40 patients undergoing epi-off CXL (31 men; 9 women; mean [SD] age, 31 [10] years), wound healing was significantly faster in the matrix therapy agent group compared with the hyaluronic acid group (4.4 vs 6.1 days; mean difference, 1.7 days; 95% CI, 0.25-3.15 days; P = .008). The defect size was smaller in the matrix therapy agent group than in the hyaluronic acid group as measured with OCT (12.4 vs 23.9 mm2; mean difference, 11.6 mm2; 95% CI, 0.8-23.5 mm2; P = .045) and SLP (11.9 vs 23.5 mm2; mean difference, 11. 6 mm2; 95% CI, 1.3-22.9 mm2; P = .03). A correlation between the defect size measured with OCT and SLP was found (r = 0.89; P < .001). No ocular or serious adverse events occurred.

Conclusions and relevance: Use of a new matrix therapy agent appears to improve corneal wound healing after CXL in patients with keratoconus. Monitoring of corneal wound healing using ultrahigh-resolution OCT might be an attractive alternative to SLP because OCT provides an objective and 3-dimensional evaluation of the corneal defect.

Trial registration: clinicaltrials.gov Identifier: NCT02119039.

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Clerapliq – Topical Treatment with a New Matrix Therapy Agent

Clerapliq – Topical Treatment with a New Matrix Therapy Agent

Abdelouahab Aifa, Julie Gueudry, Alexandre Portmann, Agn`es Delcampe, and Marc Muraine

PURPOSE. Neurotrophic keratopathy is a degenerative disease of the corneal epithelium resulting from impaired corneal innervation, possibly leading to perforation. We aimed to assess the efficacy and tolerance of a new matrix therapy agent (RGTA, Cacicol20), mimicking heparan sulfates, for the management of neurotrophic keratopathy.

METHODS. We carried out an uncontrolled, prospective, single- center clinical study on 11 patients (11 eyes) with severe corneal neurotrophic ulcers, despite the use of preservative- free artificial tears, for 15 days. Patients were treated with RGTA eye drops, instilled at a dosage of one drop in the morning, on alternate days. Evolution and follow-up during treatment were evaluated by slit-lamp examination, photogra- phy, fluorescein-dye testing, tests of corneal sensitivity, and best corrected visual acuity. The main outcome measures for each patient were healing of the corneal surface and best corrected visual acuity before and after RGTA therapy.

RESULTS. Eight patients displayed complete corneal healing after a mean period of 8.7 weeks (range; 1 to 22 weeks). Mean ulcer area decreased significantly, from 11.12% to 6.37% (P 1⁄4 0.048) in the first week, and to 1.56% (P 1⁄4 0.005) at 1 month. Treatment failure was observed in three cases, requiring amniotic membrane transplantation in two patients and penetrating keratoplasty in one patient. At the end of the study, none of the patients displayed significant improvement in visual acuity. There were no systemic or local side effects of treatment.

CONCLUSIONS. RGTA seems to be a potentially useful, alternative, noninvasive therapeutic approach in neurotrophic keratopathy management. However, randomized studies are necessary.

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Clerapliq – L’essentiel (FR)

Clerapliq -Prise en charge médicale des ulcères cornéens avec RGTA

Cas clinique – L’Essentiel

Bertrand Michaud – Docteur vétérinaire

Les ulcères cornéens sont des affections fréquemment rencontrées en pratique vétérinaire quotidienne. Leur trai- tement passe par la mise en évidence de l’origine de la lésion. Ainsi, le traitement devra être adapté à la cause, il n’y a pas de recette pré-établie, seul le sens clinique du praticien et un suivi régulier permettront de traiter correc- tement l’ulcère.

Une nouvelle classe de molécules est récemment appa- rue dans le traitement des ulcères cornéens et de la cica- trisation des tissus en général, les RGTA (ReGeneraTing Agents – Clerapliq®). Nous expliquerons les modalités d’action de l’OTR4120 et son intérêt en les illustrant par trois cas cliniques.

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