Contributions
Abstract: EP1659
Type: ePoster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Acute multiple sclerosis (MS) relapses are a major factor that contributes to permanent neurological disability in MS patients. The current use of corticosteroids in the treatment of acute relapse has no effect on the sustained residual disability. Therefore, there is a need for a better treatment of acute MS relapses to reduce relapse residual disability. Recently, we have designed an innovative Polymerase1 inhibiting compound, RAM-589.555, that suppresses ribosomal biogenesis and activates apoptosis as an innovative therapeutic approach to ameliorate MS relapse.
Objective: To evaluate effect of RAM-589.555 on B-cell apoptosis in-vitro during acute MS relapse as compared with methylprednisolone (MP).
Design and methods: CD19+ B-cells lymphocytes were obtained from relapsing-remitting (RRMS) patients during acute MS relapse. Cells were incubated for 72h with RAM-589.555 in concentration of 50 and 100 nM or with 400 mg/ml MP. Thereafter, cells were stained with Annexin V for early and Annexin/PI for late apoptosis level (MBL). Samples were analyzed by FACS Calibur (BD, Germany) and data were evaluated using FLowJo software (USA).
Results: Five RRMS patients, age 40.8±3.1 years, disease duration 9.1±1.6 years and EDSS increase during relapse >=2.0 were included in the study. Incubation of B-cells with 50 and 100 nM RAM-589.555 or 400 mg/ml MP increased early apoptosis by 2.6 (p=0.002), 3.5 (p=0.001) and 2.5 (p=0.01) folds, respectively. Late apoptosis of B-cells were increased by 7.5 (p=4.69E-06) and 8.9 (5.73E-06) times using 50 and 100 nM RAM-589.555 respectively, and significantly less by MP (p=0.01).
Conclusion: As compared to MP, RAM-589.555 significantly increased late apoptosis of B-cells obtained from RRMS patients in acute relapse. These findings suggest RAM-589.555 as a potential treatment for acute MS relapse.
Disclosure:
Michael Gurevich: contracted research (Biogen Idec, Teva, Merck)
Anat Achiron: Consulting fees (EMD Serono, Genzyme, Roche); contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Anna Feldman: nothing to disclose
Abstract: EP1659
Type: ePoster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Acute multiple sclerosis (MS) relapses are a major factor that contributes to permanent neurological disability in MS patients. The current use of corticosteroids in the treatment of acute relapse has no effect on the sustained residual disability. Therefore, there is a need for a better treatment of acute MS relapses to reduce relapse residual disability. Recently, we have designed an innovative Polymerase1 inhibiting compound, RAM-589.555, that suppresses ribosomal biogenesis and activates apoptosis as an innovative therapeutic approach to ameliorate MS relapse.
Objective: To evaluate effect of RAM-589.555 on B-cell apoptosis in-vitro during acute MS relapse as compared with methylprednisolone (MP).
Design and methods: CD19+ B-cells lymphocytes were obtained from relapsing-remitting (RRMS) patients during acute MS relapse. Cells were incubated for 72h with RAM-589.555 in concentration of 50 and 100 nM or with 400 mg/ml MP. Thereafter, cells were stained with Annexin V for early and Annexin/PI for late apoptosis level (MBL). Samples were analyzed by FACS Calibur (BD, Germany) and data were evaluated using FLowJo software (USA).
Results: Five RRMS patients, age 40.8±3.1 years, disease duration 9.1±1.6 years and EDSS increase during relapse >=2.0 were included in the study. Incubation of B-cells with 50 and 100 nM RAM-589.555 or 400 mg/ml MP increased early apoptosis by 2.6 (p=0.002), 3.5 (p=0.001) and 2.5 (p=0.01) folds, respectively. Late apoptosis of B-cells were increased by 7.5 (p=4.69E-06) and 8.9 (5.73E-06) times using 50 and 100 nM RAM-589.555 respectively, and significantly less by MP (p=0.01).
Conclusion: As compared to MP, RAM-589.555 significantly increased late apoptosis of B-cells obtained from RRMS patients in acute relapse. These findings suggest RAM-589.555 as a potential treatment for acute MS relapse.
Disclosure:
Michael Gurevich: contracted research (Biogen Idec, Teva, Merck)
Anat Achiron: Consulting fees (EMD Serono, Genzyme, Roche); contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Anna Feldman: nothing to disclose