Exciting news on the front lines of Amyotrophic Lateral Sclerosis (ALS) research! A recent study has identified a class of FDA-approved drugs, known as sartans, as potential powerful tools to combat the neuroinflammation that drives this devastating disease. Specifically, the common blood pressure medication telmisartan has shown remarkable promise in pre-clinical models. Understanding ALS and …
Exciting news on the front lines of Amyotrophic Lateral Sclerosis (ALS) research! A recent study has identified a class of FDA-approved drugs, known as sartans, as potential powerful tools to combat the neuroinflammation that drives this devastating disease. Specifically, the common blood pressure medication telmisartan has shown remarkable promise in pre-clinical models.
Understanding ALS and Neuroinflammation
ALS is a fatal neurodegenerative disease that relentlessly attacks motor neurons (MNs), the nerve cells responsible for controlling voluntary muscle movement. As these motor neurons progressively die, individuals lose the ability to move, speak, eat, and eventually breathe.
One of the most common genetic causes of ALS is a specific genetic mutation called a hexanucleotide repeat expansion in the C9orf72 gene (C9-ALS). This genetic flaw disrupts the normal function of microglia, which are specialized immune cells in the brain and spinal cord. When microglia go awry, they contribute to neuroinflammation – a chronic inflammation within the nervous system that is a key driver of ALS progression.
A New 3D Model and a Surprising Discovery
To better understand and combat C9-ALS, researchers developed an innovative three-dimensional spinal microtissue (SM) model. This sophisticated model incorporates human induced pluripotent stem cell (hiPSC)-derived motor neurons, astrocytes (another type of brain cell), and microglia, providing a more realistic environment to study the disease outside of the body.
Using this cutting-edge model, the scientists screened a vast library of 190 FDA-approved compounds – drugs already deemed safe for human use. This approach significantly speeds up the drug discovery process.
Their efforts led to a groundbreaking discovery: sartans, also known as angiotensin II receptor I blockers (ARBs), emerged as potent inhibitors of neuroinflammation.
Telmisartan: A Promising Candidate
Among the sartans, telmisartan stood out. This particular ARB is known for its ability to effectively cross the blood-brain barrier, making it an excellent candidate for targeting brain diseases.
In the C9-ALS SM models, telmisartan significantly:
- Reduced the levels of pro-inflammatory cytokines like interleukin (IL)-6 and IL-8, which are key chemical messengers that fuel inflammation.
- Rescued motor neuron loss, helping to preserve the vital cells that are destroyed in ALS.
The Implications
These findings strongly suggest that the dysfunctional microglia in C9-ALS are directly contributing to the death of motor neurons. Crucially, the study demonstrates that telmisartan can effectively mitigate this inflammation and protect motor neuron viability.
This groundbreaking work not only provides a valuable new model for studying disease-related neuroinflammation but also points to telmisartan as a highly promising therapeutic candidate for treating C9-ALS.
What This Means for the Future
While these results are from pre-clinical studies and further research, including clinical trials in humans, is needed, the discovery of an existing, FDA-approved drug with the potential to target a fundamental aspect of ALS is incredibly exciting. It offers a ray of hope for individuals living with C9-ALS and their families, potentially paving the way for new and effective treatment strategies.
Telmisartan is neuroprotective in a hiPSC-derived spinal microtissue model for C9orf72 ALS via inhibition of neuroinflammation
Sonustun, Berkiye et al.
Stem Cell Reports, Volume 0, Issue 0, 102535Stay tuned for more updates as this promising research continues to unfold!
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