A protein known as TDP-43 is lost from its usual cell nucleus location in nearly every case of amyotrophic lateral sclerosis (ALS) and up to half of Alzheimer’s disease (AD) and frontotemporal dementia cases.
This then triggers the loss of a key protein, stathmin-2, which is crucial for the regeneration of neurons and maintaining their connections with muscle fibers. This maintenance is critical for contraction and movement.
In a recent study published in Science, though, a team of researchers found that designer DNA drugs could rescue stathmin-2 loss and restore normal protein-encoding RNA processing.
“With mouse models that we engineered to misprocess their stathmin-2 encoding RNAs, like in these human diseases, we show that administration of one of these designer DNA drugs into the fluid that surrounds the brain and spinal cord restores normal stathmin-2 levels throughout the nervous system,” explained Don Cleveland, the study’s senior author.
Cleveland himself is widely credited with conceptualizing designer DNA drugs. They essentially work to turn on or turn off specific genes that are associated with various degenerative diseases, such as AD, ALS, cancer, and Huntington’s disease.
There are numerous designer DNA drugs currently undergoing clinical trials for several diseases. One drug has even been approved to treat spinal muscular atrophy– a childhood neurodegenerative disease.
This new study has built on Cleveland’s research regarding the role of TDP-43 and what happens when this protein is lost.
In cases of ALS, the loss of TDP-43 affects motor neurons that trigger skeletal muscle contractions– causing degeneration and eventually paralysis.
“In almost all instances of ALS, there is an aggregation of TDP-43, a protein that functions in the maturation of the RNA intermediates that encode many proteins,” Cleveland detailed.
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