siRNAs May Help Reduce Neuro-inflammation In Patients With Alzheimer’s Disease.
In a significant stride toward combating neuro-inflammation, researchers have explored the potential of small interfering RNAs (siRNAs) to silence the translation machinery of specific mRNAs, consequently halting the production of certain proteins (Source: Medical News today.) This breakthrough holds promise for addressing neurological conditions, including Alzheimer’s disease, where inflammation in the brain plays a pivotal role.
The delivery system devised by the researchers is particularly noteworthy, as it opens avenues for future investigations into gene knockout strategies for microglia, the immune cells of the central nervous system. SiRNAs operate by targeting the translation process of mRNAs into proteins, offering a precise mechanism to influence protein production within cells.
A major hurdle in drug development for neurological conditions is the blood-brain barrier, restricting the passage of many drugs to the brain through the bloodstream. This limitation has posed challenges in treating complex disorders like Alzheimer’s disease, where accessing the brain is crucial for therapeutic efficacy.
Despite the prevalence of Alzheimer’s disease, effective treatments remain elusive. The recent FDA approval of aducanumab, a drug targeting beta-amyloid associated with dementia, highlighted the urgency in finding viable solutions. However, neuroinflammation, identified as a hallmark of neurodegenerative disorders like Alzheimer’s, offers an alternative avenue for exploration.
Researchers honed in on PU.1, a transcription factor implicated in Alzheimer’s-related neuroinflammation. Developing an siRNA to disrupt PU.1 protein production was a significant achievement, but the challenge lay in efficiently delivering the siRNA into cells, particularly microglia. To overcome this hurdle, the team formulated seven lipid nanoparticle (LNP) formulations to transport the siRNA into the cells.
LNP formulations, previously employed in Pfizer’s mRNA COVID-19 vaccine, have demonstrated safety and efficacy. In vitro testing on human stem cell-derived microglia-like cells (iMGLs) was conducted to identify the most effective LNP formulation for delivering siRNA into the cell nucleus.
This pioneering approach not only offers a potential therapy against neuroinflammation but also showcases the adaptability of LNP formulations in facilitating precise and effective delivery of therapeutic agents.
As research in this field progresses, the integration of siRNAs and advanced delivery systems may pave the way for novel treatments targeting the intricate mechanisms underlying neuroinflammatory disorders.
Read Also:
