Abstract: 98
Type: Oral
The remarkable success of immunomodulatory therapies in relapsing forms of MS serves to heighten the need to both; 1) understand the indirect effects of suppressing inflammation for achieving neuroprotection, as well as to 2) identify the direct mechanisms underlying neuroaxonal loss to facilitate the development of therapies that might target progression of MS in the absence of overt inflammation. While mounting evidence supports the notion that anti-inflammatory therapies protect CNS tissue compartments from damage there remains an urgent need for tools that the clinician can use at the bedside to assess tissue protection outcomes in individual patients to guide therapeutic decision making processes. Furthermore, such tools will also be critical for testing the effects of putative neuroprotective agents in clinical trials.
A number of imaging outcome measures have the potential to reproducibly quantify tissue loss in neuronal and axonal enriched structures of the anterior and posterior visual pathways. One approach is optical coherence tomography (OCT), which has the desirable features of simplicity of acquisition, reproducibility across centers, and has been validated in both cross-sectional and longitudinal datasets by many investigators. A recent meta-analysis showed that OCT measures of the retina predict 5 year clinical outcomes, and a smaller cohort presented as a platform in this meeting now reveals that a baseline OCT can predict progression on EDSS ten years later. Additional measures of the visual pathway that corroborate these data include; MRI derived volumes of the optic nerve, thalamus and visual cortex. Physiological and functional outcome measurements, including resting state fMRI, spectroscopy, and electrophysiology are also revealing measurable pathology, which will add complementary information to our understanding of the dynamic aspect of disease progression.
While imaging and functional tools can provide accurate measures of pathology that may help to overcome the inherent noise in routine clinical assessments, they ultimately will need to be studied in concert with biomarkers that allow mechanistic understanding of the disease process. In this regard, there are ongoing projects to incorporate genomic and metabolomic experiments with OCT and MRI, in order to leverage the sensitivity of imaging and enable the identification of specific neuronal and glial molecular pathways involved in mediating neurodegeneration in MS.
Disclosure: Dr. Calabresi has received consulting fees from Vertex and grants to support research at Johns Hopkins from Biogen, MedImmune and Novartis.
Abstract: 98
Type: Oral
The remarkable success of immunomodulatory therapies in relapsing forms of MS serves to heighten the need to both; 1) understand the indirect effects of suppressing inflammation for achieving neuroprotection, as well as to 2) identify the direct mechanisms underlying neuroaxonal loss to facilitate the development of therapies that might target progression of MS in the absence of overt inflammation. While mounting evidence supports the notion that anti-inflammatory therapies protect CNS tissue compartments from damage there remains an urgent need for tools that the clinician can use at the bedside to assess tissue protection outcomes in individual patients to guide therapeutic decision making processes. Furthermore, such tools will also be critical for testing the effects of putative neuroprotective agents in clinical trials.
A number of imaging outcome measures have the potential to reproducibly quantify tissue loss in neuronal and axonal enriched structures of the anterior and posterior visual pathways. One approach is optical coherence tomography (OCT), which has the desirable features of simplicity of acquisition, reproducibility across centers, and has been validated in both cross-sectional and longitudinal datasets by many investigators. A recent meta-analysis showed that OCT measures of the retina predict 5 year clinical outcomes, and a smaller cohort presented as a platform in this meeting now reveals that a baseline OCT can predict progression on EDSS ten years later. Additional measures of the visual pathway that corroborate these data include; MRI derived volumes of the optic nerve, thalamus and visual cortex. Physiological and functional outcome measurements, including resting state fMRI, spectroscopy, and electrophysiology are also revealing measurable pathology, which will add complementary information to our understanding of the dynamic aspect of disease progression.
While imaging and functional tools can provide accurate measures of pathology that may help to overcome the inherent noise in routine clinical assessments, they ultimately will need to be studied in concert with biomarkers that allow mechanistic understanding of the disease process. In this regard, there are ongoing projects to incorporate genomic and metabolomic experiments with OCT and MRI, in order to leverage the sensitivity of imaging and enable the identification of specific neuronal and glial molecular pathways involved in mediating neurodegeneration in MS.
Disclosure: Dr. Calabresi has received consulting fees from Vertex and grants to support research at Johns Hopkins from Biogen, MedImmune and Novartis.