Abstract: P1271
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: An increasing body of evidence suggests neuroaxonal damage to be the main determinant of long term disability. Among different markers of neuroaxonal damage neurofilament light (NFL) has emerged as a promising biomarker candidate. Still, an important obstacle for a wider introduction into clinical practice is that such analyses have required access to cerebrospinal fluid (CSF). Detection of NFL in serum or plasma have been reported previously, however, most technical platforms have an analytical sensitivity limit above levels normally seen in healthy controls and with a significant overlap with levels seen in MS patients.
Objective: To (i) determine the correlation between NFL in CSF and serum/plasma in a pilot cohort of MS patients and controls, and (ii) to determine levels of NFL in plasma at baseline and at 12 months of patients starting treatment with fingolimod (Gilenya).
Methods: We applied the Single Molecule Array (Simoa) technology for ultrasensitive detection of NFL using antibodies from UmanDiagnostics (UmanDiagnostics, Umeå, Sweden) transferred onto the Simoa platform using a homebrew kit (Quanterix Corp, Boston, MA, USA). The lower limit of quantification (LLoQ), determined by the blank mean signal + 10 SD was 1.95 pg/ml.
Results: The correlation between serum and CSF levels was high both in controls with non-inflammatory neurological conditions (Spearman rank test, Sr=0.759; p< 0.0001; n=27) and MS patients (Sr=0.5776; p< 0.0001; n=46). Furthermore, plasma and serum levels in MS patients were also highly correlated (Sr=0.684; p< 0.007; n=14). In patients being either treatment naïve or switching from injectable disease modulatory treatments the plasma level of NFL decreased significantly (baseline mean 26.4 ± 6.81 pg/ml, 12 months mean 22.3 ± 5.81; Paired T test, two tailed, p=0.004; n=30). Additional data on a cohort of 200 patients with correlation to clinical and treatment related outcomes will be included in the final presentation.
Conclusions: We here report a high correlation of CSF NFL levels in CSF and plasma/serum of MS patients and controls using an ultrasensitive analysis platform. Furthermore, plasma levels of NFL were significantly reduced at 12 months compared with baseline in MS patients initiating fingolimod treatment. The results suggest that NFL levels in plasma can be used to monitor treatment effectiveness in MS patients.
Disclosure: Fredrik Piehl: has received unrestricted academic research grants from Biogen, Genzyme and Novartis, and travel support and/or compensation for lectures and/or participation in advisory boards from Biogen, Merckserono, Novartis, Genzyme and Teva, which have been exclusively used for the support of research activities.
Ingrid Kockum: Nothing to disclose
Mohsen Khademi:Nothing to disclose
Kaj Blennow:Nothing to disclose
Niklas Norgren:is an employee of Uman Diagnostics AB, Umeå, Sweden
Henrik Zetterberg: has received an unrestricted academic research grant from Novartis,
Tomas Olsson: has received compensation for lectures and /or advisory boards, or unrestricted MS research grants from Biogen, Allmiral, Novartis, Genzyme, Astrazeneca and MerckSerono.
Abstract: P1271
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: An increasing body of evidence suggests neuroaxonal damage to be the main determinant of long term disability. Among different markers of neuroaxonal damage neurofilament light (NFL) has emerged as a promising biomarker candidate. Still, an important obstacle for a wider introduction into clinical practice is that such analyses have required access to cerebrospinal fluid (CSF). Detection of NFL in serum or plasma have been reported previously, however, most technical platforms have an analytical sensitivity limit above levels normally seen in healthy controls and with a significant overlap with levels seen in MS patients.
Objective: To (i) determine the correlation between NFL in CSF and serum/plasma in a pilot cohort of MS patients and controls, and (ii) to determine levels of NFL in plasma at baseline and at 12 months of patients starting treatment with fingolimod (Gilenya).
Methods: We applied the Single Molecule Array (Simoa) technology for ultrasensitive detection of NFL using antibodies from UmanDiagnostics (UmanDiagnostics, Umeå, Sweden) transferred onto the Simoa platform using a homebrew kit (Quanterix Corp, Boston, MA, USA). The lower limit of quantification (LLoQ), determined by the blank mean signal + 10 SD was 1.95 pg/ml.
Results: The correlation between serum and CSF levels was high both in controls with non-inflammatory neurological conditions (Spearman rank test, Sr=0.759; p< 0.0001; n=27) and MS patients (Sr=0.5776; p< 0.0001; n=46). Furthermore, plasma and serum levels in MS patients were also highly correlated (Sr=0.684; p< 0.007; n=14). In patients being either treatment naïve or switching from injectable disease modulatory treatments the plasma level of NFL decreased significantly (baseline mean 26.4 ± 6.81 pg/ml, 12 months mean 22.3 ± 5.81; Paired T test, two tailed, p=0.004; n=30). Additional data on a cohort of 200 patients with correlation to clinical and treatment related outcomes will be included in the final presentation.
Conclusions: We here report a high correlation of CSF NFL levels in CSF and plasma/serum of MS patients and controls using an ultrasensitive analysis platform. Furthermore, plasma levels of NFL were significantly reduced at 12 months compared with baseline in MS patients initiating fingolimod treatment. The results suggest that NFL levels in plasma can be used to monitor treatment effectiveness in MS patients.
Disclosure: Fredrik Piehl: has received unrestricted academic research grants from Biogen, Genzyme and Novartis, and travel support and/or compensation for lectures and/or participation in advisory boards from Biogen, Merckserono, Novartis, Genzyme and Teva, which have been exclusively used for the support of research activities.
Ingrid Kockum: Nothing to disclose
Mohsen Khademi:Nothing to disclose
Kaj Blennow:Nothing to disclose
Niklas Norgren:is an employee of Uman Diagnostics AB, Umeå, Sweden
Henrik Zetterberg: has received an unrestricted academic research grant from Novartis,
Tomas Olsson: has received compensation for lectures and /or advisory boards, or unrestricted MS research grants from Biogen, Allmiral, Novartis, Genzyme, Astrazeneca and MerckSerono.