BACKGROUND: In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression. OBJECTIVE: The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13). METHODS: CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays. RESULTS: The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline. CONCLUSIONS: Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in phase II trials of MS.
BACKGROUND: In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression. OBJECTIVE: The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13). METHODS: CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays. RESULTS: The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline. CONCLUSIONS: Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in phase II trials of MS.
Authors: Shahin Aeinehband; Rickard P F Lindblom; Faiez Al Nimer; Swetha Vijayaraghavan; Kerstin Sandholm; Mohsen Khademi; Tomas Olsson; Bo Nilsson; Kristina Nilsson Ekdahl; Taher Darreh-Shori; Fredrik Piehl Journal: PLoS One Date: 2015-04-02 Impact factor: 3.240
Authors: Renan Barros Domingues; Gustavo Bruniera Peres Fernandes; Fernando Brunale Vilela de Moura Leite; Charles Peter Tilbery; Rodrigo Barbosa Thomaz; Gisele Sampaio Silva; Cristóvão Luis Pitangueira Mangueira; Carlos Augusto Senne Soares Journal: Einstein (Sao Paulo) Date: 2017 Jan-Mar
Authors: Faiez Al Nimer; Christina Elliott; Joakim Bergman; Mohsen Khademi; Ann M Dring; Shahin Aeinehband; Tommy Bergenheim; Jeppe Romme Christensen; Finn Sellebjerg; Anders Svenningsson; Christopher Linington; Tomas Olsson; Fredrik Piehl Journal: Neurol Neuroimmunol Neuroinflamm Date: 2016-01-07
Authors: Lenka Novakova; Henrik Zetterberg; Peter Sundström; Markus Axelsson; Mohsen Khademi; Martin Gunnarsson; Clas Malmeström; Anders Svenningsson; Tomas Olsson; Fredrik Piehl; Kaj Blennow; Jan Lycke Journal: Neurology Date: 2017-10-27 Impact factor: 9.910