Researchers have developed a novel laboratory model using stem cells derived from the skin of individuals with progressive multiple sclerosis (PMS) to investigate the role of cholesterol in nerve damage. The study, published in Cell Stem Cell, reveals that elevated cholesterol levels in neural stem cells can have detrimental effects on nerves, potentially contributing to the progression of PMS. The findings suggest that cholesterol-lowering drugs like simvastatin could mitigate these harmful effects, offering a new treatment avenue for PMS.
Uncovering the Role of Cholesterol in Progressive MS
Progressive MS is characterized by a steady worsening of symptoms over time, leading to increasing disability. Researchers are focused on understanding the underlying mechanisms that drive nerve damage in PMS, particularly the changes occurring within brain cells. As cells age, they can acquire harmful traits and lose their natural balance, affecting their function. Studies have shown that aging cells accumulate in the brains of older adults and individuals with neurodegenerative diseases.
When cells are injured or affected by disease, they adapt by reprogramming themselves, taking on early-stage characteristics and entering a new state. This can lead to alterations in energy processing and signs of aging. This study specifically examined whether increased cholesterol production in certain brain cells contributes to nerve damage and whether simvastatin, a common cholesterol-lowering medication, could help.
Modeling PMS in the Lab
The scientists created a model using skin cells (fibroblasts) from individuals with PMS. These fibroblasts were reprogrammed into induced neural stem cells, mimicking the behavior of the brain's natural neural stem cells. This allowed the researchers to compare the function of these cells in PMS patients versus those without MS. They examined how the cells processed energy (from glucose) and produced cholesterol, observing the effects on the surrounding environment. The researchers also tested whether simvastatin could reduce the harmful effects observed in the PMS cells.
Key Findings: Cholesterol and Inflammation
The researchers discovered that stem cells from individuals with PMS were more active in breaking down sugar and producing cholesterol compared to those from individuals without MS. This increased cholesterol production led to the accumulation of fat droplets within the cells and triggered the release of inflammatory substances, which could harm surrounding nerve cells. This inflammation may exacerbate nerve damage and contribute to the progression of PMS.
Treatment with simvastatin helped reduce the release of these harmful substances, creating a more protective environment for the cells. While simvastatin did not completely reverse all the changes in the cells, it significantly reduced their negative impact on nearby nerve cells.
Implications for PMS Treatment
These findings offer hope for individuals living with PMS, a form of MS with limited treatment options compared to relapsing-remitting MS (RRMS). The study suggests that controlling cholesterol levels within certain brain cells might protect against nerve damage and slow down the progression of disability. Simvastatin, a widely used medication, could potentially play a new role in managing PMS, benefiting both cardiovascular and brain health.
It is important to note that recent findings from the MS-STAT2 trial, a phase III study presented at ECTRIMS 2024, indicated that simvastatin was not effective in treating secondary progressive MS in its cohort of participants. While the MS-STAT2 results are important, this cellular study provides valuable insights into the underlying mechanisms of PMS. The novel technique of using skin cells from individuals with PMS to create neural stem cells allows researchers to investigate how brain cells respond to cholesterol imbalance at a cellular level, potentially identifying new therapeutic targets. While these findings are at the cellular level, understanding these small-scale changes can inform broader research aimed at whole-body effects in PMS.
While this research does not represent a cure for MS, it marks an exciting step forward in understanding the condition. It also highlights the potential of repurposing existing medications to improve the lives of individuals with MS. Further research could pave the way for new treatment options, bringing us closer to effectively managing PMS and enhancing overall quality of life.
