Contributions
Abstract: P705
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Objective: Fingolimod is the first oral compound approved in the US, Canada and the EU for the treatment of Relapsing Remitting Multiple Sclerosis (RRMS). Inducing a S1P1 down-regulation that prevents lymphocyte egress from lymphoid tissues, it is considered an immunosuppressive agent. We used a well-defined experimental model to assess Fingolimod effects on cutaneous wound healing, a physiological process that involves neutrophils, lymphocytes and macrophages.
Background: Immunosuppressants are known to interfere with surgical wound healing. This is the case of Azathioprine, another oral drug labeled in Spain to treat RRMS. The increasing use of immunosuppressive drugs in MS asks for a better understanding of their effects on wound healing.
Design and methods: Sixty-three Sprague-Dawley rats received Fingolimod 0.3 mg/kg/day (n=21), Azathioprine 1.5mg/kg/day (n=21) or sham (n=21) for 6 weeks before a 2 cm linear dorsal surgical wound closed with surgical staples or a circular 2 cm diameter defect were performed. Animals were still receiving treatment for 7 (n=21, linear wound) and 21 (n=21 linear wound, N=21 circular defect) more days, until sacrifice, when surgical site tissue was collected and analyzed for optic microscopy (Masson´s tricromic), macrophage (total, M1 and M2 phenotypes) cell number (ED1) and collagen fiber content (Sirius red). Mass spectrometry was performed before surgery to confirm serum Fingolimod presence. The study followed the recommendations of the Guide for the Care and Use of Laboratory Animals of the National and European Institutes of Health.
Results: No differences were obtained with the circular defect model. Linear wound model: On day 7, Azathioprine provoked macroscopical disruption of the scar in 5/7 rats, compared to only 2/7 in the Fingolimod treated animals. Moreover, Macrophage content was lower in Azathioprine compared to Fingolimod and sham treated groups. No difference between the three groups on collagen formation was observed on day 7, but on day 21, Azathioprine group showed less collagen content.
Conclusions: Compared to Azathioprine, Fingolimod does not interfere with wound healing. Tissue repair was not delayed and is similar to the pattern observed in sham treated rats.
Disclosure: This study was funded by NOVARTIS PHARMA.
Dr. Ricardo C. Ginestal received compensation from Merck-Serono, Biogen-Idec, TEVA, Novartis and Bayer-Schering for consulting services, scientific advisory board and conference speaking.
Dr. Perez-Köhler: nothing to disclose.
Dr. Perez-Lopez: nothing to disclose.
Dr. Pascual-Gonzalez: nothing to disclose.
Dr. Rodríguez-Mancheno: nothing to disclose.
Dr. Cebrian: nothing to disclose.
Dr. Garcia-Moreno: nothing to disclose.
Dr. Bellon-Caneiro: nothing to disclose.
Abstract: P705
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Objective: Fingolimod is the first oral compound approved in the US, Canada and the EU for the treatment of Relapsing Remitting Multiple Sclerosis (RRMS). Inducing a S1P1 down-regulation that prevents lymphocyte egress from lymphoid tissues, it is considered an immunosuppressive agent. We used a well-defined experimental model to assess Fingolimod effects on cutaneous wound healing, a physiological process that involves neutrophils, lymphocytes and macrophages.
Background: Immunosuppressants are known to interfere with surgical wound healing. This is the case of Azathioprine, another oral drug labeled in Spain to treat RRMS. The increasing use of immunosuppressive drugs in MS asks for a better understanding of their effects on wound healing.
Design and methods: Sixty-three Sprague-Dawley rats received Fingolimod 0.3 mg/kg/day (n=21), Azathioprine 1.5mg/kg/day (n=21) or sham (n=21) for 6 weeks before a 2 cm linear dorsal surgical wound closed with surgical staples or a circular 2 cm diameter defect were performed. Animals were still receiving treatment for 7 (n=21, linear wound) and 21 (n=21 linear wound, N=21 circular defect) more days, until sacrifice, when surgical site tissue was collected and analyzed for optic microscopy (Masson´s tricromic), macrophage (total, M1 and M2 phenotypes) cell number (ED1) and collagen fiber content (Sirius red). Mass spectrometry was performed before surgery to confirm serum Fingolimod presence. The study followed the recommendations of the Guide for the Care and Use of Laboratory Animals of the National and European Institutes of Health.
Results: No differences were obtained with the circular defect model. Linear wound model: On day 7, Azathioprine provoked macroscopical disruption of the scar in 5/7 rats, compared to only 2/7 in the Fingolimod treated animals. Moreover, Macrophage content was lower in Azathioprine compared to Fingolimod and sham treated groups. No difference between the three groups on collagen formation was observed on day 7, but on day 21, Azathioprine group showed less collagen content.
Conclusions: Compared to Azathioprine, Fingolimod does not interfere with wound healing. Tissue repair was not delayed and is similar to the pattern observed in sham treated rats.
Disclosure: This study was funded by NOVARTIS PHARMA.
Dr. Ricardo C. Ginestal received compensation from Merck-Serono, Biogen-Idec, TEVA, Novartis and Bayer-Schering for consulting services, scientific advisory board and conference speaking.
Dr. Perez-Köhler: nothing to disclose.
Dr. Perez-Lopez: nothing to disclose.
Dr. Pascual-Gonzalez: nothing to disclose.
Dr. Rodríguez-Mancheno: nothing to disclose.
Dr. Cebrian: nothing to disclose.
Dr. Garcia-Moreno: nothing to disclose.
Dr. Bellon-Caneiro: nothing to disclose.