Multiple sclerosis-derived induced pluripotent stem cells

Funding Type: 
Tissue Collection for Disease Modeling
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Multiple sclerosis (MS) is a disease of the central nervous system; it is the most common cause of non-traumatic neurological disability in young adults, affecting approximately 2 million people worldwide. The incidence of MS appears to have increased considerably over the last century. In most cases, MS starts out as a relapsing-remitting disease with episodes during which neurological symptoms occur and persist for days to months and are followed by symptom-free intervals. After 10 to 15 years, a large percentage of patients begin to accumulate neurological disability and follow a progressively worsening disease course. Together with tissue changes observed in the brain and spinal cord of MS patients, this suggests inflammation and neurodegeneration to participate in MS pathology. MS is a prototypical complex genetic disease as multiple so-called "susceptibility loci" have been identified. The ensuing challenge is to design effective functional studies that link genetic variation to the underlying pathophysiology of MS. Such knowledge might translate into clinically useful genetic biomarkers and reveal novel targets for therapy. The availability of a representative panel of MS hiPSCs will undoubtedly aid in this effort. We plan to recruit tissue donors from a cohort of MS patients followed at[REDACTED]. These patients are extremely well studied and extensive clinical, imaging, laboratory, and genetic data information is available for each study participant

Statement of Benefit to California: 

Multiple sclerosis (MS) is a debilitating disease leading to significant neurological disability in about about 80% of patients within 15 years after diagnosis. MS mainly affects young adults aged 20 to 30 years-old; there are more than 50,000 MS patients living in California. MS symptoms are caused by inflammatory myelin destruction and neurodegenerative mechanisms. Our understanding of inflammatory activity in MS has led to the development of numerous treatments that reduce disease activity. However, our understanding of neurodegenerative processes occurring in MS patients and why in these patients the brain's ability to self-repair ultimately fails and permits accumulating neurological deficitis and disability, remains very limited. MS is a disease with a complex genetic background. As more-and-more genes are being identified that may be involved in the disease process, we begin to learn about genes that may be particularly important to the neurodengenerative aspect of the disease. The availability of a large cohort of clinically, genetically, and by imaging studies well-studied MS patients in [REDACTED], directly permits selection of patients carrying specific genetic markers. This study will obtain tissues from 100 MS patients based disease-course and genetic data to generate hiPSC which can then be used to better model MS. Understanding how to better repair brain or prevent lasting damage and disability will ultimately improve the lives and ability to work of many.