UCLA

Multiple sclerosis (MS) affects more than 1 million Americans every year and is a chronic, demyelinating, neurodegenerative disease of the central nervous system. MS is a challenging disease to diagnose and treat as it can be a heterogenous in both its biological aspects and clinical presentation. Standard of care for diagnosing patients with MS is through the use of magnetic resonance imaging (MRI). While this technique is informative about anatomical structures, an imaging modality that can provide functional information about the disease will help to elucidate the complex mechanisms involved. Furthermore, current therapies for MS can have significant side effects on patients and/or only target a certain subset of patients. New therapies are needed to not only help MS patients but also patients with other autoimmune diseases.

Chapter one of this dissertation will be a review about the current state of MS, introduction into positron emission tomography (PET) and the current radiotracers that have been developed to image different aspects of MS, and the deoxyribonucleoside salvage pathway in autoimmunity.

Chapter two describes the first project that I worked on in which I utilize [18F]FAC to image brain-infiltrating leukocytes in the experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Brain-filtrating leukocytes contributes to MS pathology and have been shown to contribute to pathology in other neurological diseases including autoimmune encephalomyelitis. Because of its role in disease pathology, it is of importance that a strategy is available to image these pathogenic immune cells.

Chapter three will talk about understanding the functional aspect of the deoxyribonucleoside salvage in EAE and the broader implications of this pathway for MS disease. Through our previous work on imaging this pathway in EAE, we found that this pathway is upregulated during disease onset and progression. I show that in this chapter the deoxyribonucleoside salvage is functionally-relevant for EAE and that specifically targeting this pathway in EAE leads to improvement of clinical symptoms in MS. Discoveries made here can be translated into understanding and developing therapies for other autoimmune diseases. The result of this work demonstrates the potential of targeting the deoxyribonucleoside salvage in autoimmune diseases and the success of this target in MS mouse models support further evaluation into the clinical for patients with autoimmune diseases.

In chapter 4, I draw conclusions to my work during this PhD and in chapter 5, I highlight some of the works that I have contributed to during my time at UCLA.