Contributions
Abstract: P778
Type: Poster
Abstract Category: Therapy - disease modifying - 30 Tools for detecting therapeutic response
Background and aims: The systemic anti-inflammatory action of Dimethyl fumarate (DMF) is hypothesized to be partly due to its modulation of glutathione levels. Its impact on neurometabolite profiles and anti-inflammatory status of the brain is less understood. In this study we applied non-invasive 1H-MRS to evaluate hippocampal neurometabolite changes in RRMS patients compared to healthy controls(HCs) and then assessed changes associated with DMF treatment over time.
Methods: 1H-MRS was undertaken on 20 RRMS patients prior to treatment onset (baseline) and at 1, 6 and 12 months post-inception of DMF treatment and 20 age and sex-matched healthy controls, using a Siemens Prisma 3T MRI scanner. Spectroscopic data were acquired by using single voxel spectroscopy (6.75mL, PRESS, TE 30ms). Hippocampal metabolite to total creatine ratios of 5 neurometabolites of interest were derived using LCModel(v6.2-2B), this included: N-acetylaspartate(NAA), glutamine+glutamate, glutathione(GSH), myo-inositol(mI), and phosphocreatine. Comparisons of mean metabolite levels between controls and the RRMS group at baseline were undertaken using T-tests. In the patient group at baseline, bivariate correlation analysis evaluated association of clinical covariates with each metabolite. Changes in metabolite levels during treatment was performed using repeated measures ANOVA, adjusted for appropriate covariates, followed by post hoc testing using least significant difference.
Results: We identified a significant decrease in hippocampal NAA (13%, P=0.0001) and increase in mI (+9%, P=0.02) in RRMS patients at baseline compared to HCs.Following DMF treatment, mean hippocampal GSH levels differed over 12 months of treatment (F=2.8, P< 0.05). There was a significant reduction in GSH from baseline to 1 month of treatment (0.6±0.06 vs 0.43±0.04, respectively) (P=0.014). This reduction remained statistically significant after 6 months of treatment (0.45±0.03, P=0.035), but slightly increased after 12 months to approach levels seen in HCs (0.48±0.04, P=0.15). None of the other metabolites evaluated in this study showed a significant treatment effect (P>0.05).
Conclusions: Our findings suggest that DMF treatment is associated with a modification in the level of glutathione in the hippocampus. Further studies with larger patient numbers and longer treatment durations are warranted to investigate the impact of DMF on metabolic changes in the MS brain.
Disclosure:
Oun Al-iedani: Nothing to disclose.
Karen Ribbons: Funding for the study was provided by Biogen Australia Pty Ltd as an investigator-initiated trial grant.
Rod Lea: Nothing to disclose.
Saadallah Ramadan: Nothing to disclose.
Jeannette Lechner-Scott: Accepted travel compensation from Novartis, Biogen and Merck. Her institution receives the honoraria for talks and advisory board commitment from Bayer Health Care, Biogen, Genzyme Sanofit, Merck, Novartis, Teva and Roche, has been involved in clinical trials with Biogen, Novartis and Teva.
Abstract: P778
Type: Poster
Abstract Category: Therapy - disease modifying - 30 Tools for detecting therapeutic response
Background and aims: The systemic anti-inflammatory action of Dimethyl fumarate (DMF) is hypothesized to be partly due to its modulation of glutathione levels. Its impact on neurometabolite profiles and anti-inflammatory status of the brain is less understood. In this study we applied non-invasive 1H-MRS to evaluate hippocampal neurometabolite changes in RRMS patients compared to healthy controls(HCs) and then assessed changes associated with DMF treatment over time.
Methods: 1H-MRS was undertaken on 20 RRMS patients prior to treatment onset (baseline) and at 1, 6 and 12 months post-inception of DMF treatment and 20 age and sex-matched healthy controls, using a Siemens Prisma 3T MRI scanner. Spectroscopic data were acquired by using single voxel spectroscopy (6.75mL, PRESS, TE 30ms). Hippocampal metabolite to total creatine ratios of 5 neurometabolites of interest were derived using LCModel(v6.2-2B), this included: N-acetylaspartate(NAA), glutamine+glutamate, glutathione(GSH), myo-inositol(mI), and phosphocreatine. Comparisons of mean metabolite levels between controls and the RRMS group at baseline were undertaken using T-tests. In the patient group at baseline, bivariate correlation analysis evaluated association of clinical covariates with each metabolite. Changes in metabolite levels during treatment was performed using repeated measures ANOVA, adjusted for appropriate covariates, followed by post hoc testing using least significant difference.
Results: We identified a significant decrease in hippocampal NAA (13%, P=0.0001) and increase in mI (+9%, P=0.02) in RRMS patients at baseline compared to HCs.Following DMF treatment, mean hippocampal GSH levels differed over 12 months of treatment (F=2.8, P< 0.05). There was a significant reduction in GSH from baseline to 1 month of treatment (0.6±0.06 vs 0.43±0.04, respectively) (P=0.014). This reduction remained statistically significant after 6 months of treatment (0.45±0.03, P=0.035), but slightly increased after 12 months to approach levels seen in HCs (0.48±0.04, P=0.15). None of the other metabolites evaluated in this study showed a significant treatment effect (P>0.05).
Conclusions: Our findings suggest that DMF treatment is associated with a modification in the level of glutathione in the hippocampus. Further studies with larger patient numbers and longer treatment durations are warranted to investigate the impact of DMF on metabolic changes in the MS brain.
Disclosure:
Oun Al-iedani: Nothing to disclose.
Karen Ribbons: Funding for the study was provided by Biogen Australia Pty Ltd as an investigator-initiated trial grant.
Rod Lea: Nothing to disclose.
Saadallah Ramadan: Nothing to disclose.
Jeannette Lechner-Scott: Accepted travel compensation from Novartis, Biogen and Merck. Her institution receives the honoraria for talks and advisory board commitment from Bayer Health Care, Biogen, Genzyme Sanofit, Merck, Novartis, Teva and Roche, has been involved in clinical trials with Biogen, Novartis and Teva.