- Researchers developed a laboratory model using stem cells derived from the skin of people with progressive multiple sclerosis (PMS) to investigate how increased cholesterol production may contribute to nerve damage.
- They found that elevated cholesterol levels in neural stem cells could have harmful effects on nerves.
- Using a cholesterol-lowering drug, they demonstrated potential to reduce these harmful effects, suggesting a new treatment approach for PMS.
Uncovering the Hidden Drivers of Nerve Damage in Progressive MS
Researchers wanted to understand what causes nerve damage in progressive multiple sclerosis (PMS). PMS is a stage of MS where symptoms steadily get worse over time, leading to increasing disability. One key question is what changes occur inside brain cells to drive this process.
As people age, their cells also age, often gaining harmful traits and losing their natural balance, which affects how they work. Studies have shown that aging cells accumulate in the brains of older adults and people with neurodegenerative diseases.
When cells are injured or affected by disease, they adapt by reprogramming themselves. They take on early-stage characteristics and enter a new state, which can lead to changes in how they process energy and show signs of aging.
This study, published in Cell Stem Cell, specifically examined if increased cholesterol production in certain brain cells could contribute to nerve damage and explored whether a common cholesterol-lowering medication could help. Cholesterol is a fatty substance that cells need in small amounts to function, but high levels can disrupt cell processes and increase the risk of cardiovascular diseases.
What Did the Researchers Do?
The scientists created a model using skin cells, called fibroblasts, from people with PMS. The fibroblasts were ‘reprogrammed’ into stem cells, called induced neural stem cells, which behave like the brain’s natural neural stem cells. This allowed them to study how these cells function in PMS compared to cells from people without MS. The researchers examined how the cells processed energy (from glucose) and produced cholesterol, observing the effects on the cells’ surrounding environment. They also tested whether simvastatin, a common cholesterol-lowering medication, could reduce the harmful effects seen in the PMS cells.
What Did the Researchers Find?
The researchers found that the stem cells from people with PMS were more active in breaking down sugar and making cholesterol than those from people without MS. This increased cholesterol production led to the buildup of fat droplets within the cells and triggered a release of inflammatory substances, which could harm surrounding nerve cells. This inflammation may worsen nerve damage and contribute to the progression of PMS.
When the researchers used simvastatin on these cells, it helped reduce the release of these harmful substances, making the cell environment more protective. While simvastatin did not completely reverse all the changes in the cells, it did make a difference in reducing their negative impact on nearby nerve cells.
What Does this Mean for People with MS?
This study offers hope for people living with PMS, a form of MS that we know has fewer treatment options than relapsing-remitting MS (RRMS). It suggests that controlling cholesterol levels inside certain brain cells might help protect against nerve damage and slow down the progression of disability. Simvastatin, a medication familiar to many, could potentially play a new role in managing PMS, benefiting not only cardiovascular health but also brain health.
Recent findings from the MS-STAT2 trial, a phase III study presented at ECTRIMS 2024, showed that simvastatin did not prove effective in treating secondary progressive MS in its cohort of participants. These results are yet to be peer-reviewed. While the outcomes from MS-STAT2 are important, this cellular study remains valuable as it helps deepen our understanding of PMS through innovative approaches, including using skin cells from people with PMS to create neural stem cells. This novel technique allows researchers to investigate how brain cells respond to cholesterol imbalance at a cellular level, providing insights that could help target therapeutic pathways. 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 is not a cure for MS, it’s an exciting step forward in understanding the condition. It also highlights the utility of repurposing existing medications to help people with MS live healthier and more fulfilling lives. With further research, these findings could help pave the way for new treatment options, bringing us a step closer to managing PMS more effectively and improving overall quality of life.
