Multiple sclerosis (MS) is an inflammatory disease of the central nervous system. MS has a prominent neurodegenerative component that is most visible in the progressive phases of the disease and is not amenable to immunomodulatory treatments. We use a translational approach to understand mechanisms leading to neurodegeneration in MS.
Current projects are:
- Mechanisms of neurodegeneration in MS cortex
- Iron-sensitive phase/QSM imaging in multiple sclerosis patients
- Patient-specific neuronal susceptibility to inflammation
Mechanisms of neurodegeneration in MS cortexWe are using autopsy tissue from MS patients to define mechanisms of neuronal damage in cortical gray matter. I particular, we are interested in the roles of autophagy, mitochondrial dysfunction and oxidative damage in neuronal degeneration. For this, we are using a MS brain bank maintained in our laboratory.
Iron-sensitive phase/QSM imaging in multiple sclerosis patientsWith this research program we explore the role of iron accumulation in MS lesions. Iron deposition occurs during lesion development and can be visualized in MS patients with iron-sensitive magnetic resonance imaging (phase/QSM). Our work suggests that iron accumulates predominantly in activated microglia/macrophages within MS lesions and drives proinflammatory polarization. Iron-sensitive imaging is therefore likely to be indicative of low grade chronic inflammation and might be a useful tool to monitor the inflammatory status of MS patients.
Patient-specific neuronal susceptibility to inflammation
Recent advances in stem cell research, especially in induced pluripotent stem cell (iPSC) technology, lead to new opportunities for in vitro modeling of neurological diseases. A growing number of studies on familial forms of Alzheimer’s disease, Parkinson’s disease or amyotrophic lateral sclerosis (ALS) are demonstrating that aspects of these diseases can be recapitulated in patient-specific neuronal cultures in vitro.
We are applying this approach to multiple sclerosis, which has a genetically complex, multifactorial etiology. We examine whether iPSC-derived neurons from MS patients with specific clinical phenotypes differ in their vulnerability to inflammation. The goal of these experiments is to create a platform with which we can examine mechanisms of neurodegeneration in MS, prognosticate the risk for neurodegeneration in individual patients and determine the efficacy of neuroprotective treatments for a given patient, thereby creating a personalized approach to MS treatment.