"Nature Medicine" Silencing a gene accidentally found clues to the treatment of ALS

NIH-funded preclinical study identifies potential treatment for ALS

Using an experimental drug, researchers were able to suppress a mutant amyotrophic lateral sclerosis (ALS) gene

Dr.

ALS is a fatal neurological disease that causes motor neurons in the brain and spinal cord to degenerate

In this study, an antisense oligonucleotide drug was used to inhibit FUS by preventing cells from producing a specific protein, thereby delaying the onset of motor neuron degeneration in mice

Compared with normal mice, mice with mutations in the FUS gene had higher levels of insoluble FUS and other ALS-related proteins in the brain and spinal cord

This study establishes a highly disease-related mouse model where FUS toxicity is due to increased function and is dose-dependent, suggesting that we can treat FUS-ALS by silencing the FUS gene

In 2019, author Dr.

In mice, a single dose of the drug injected into the ventricle, the fluid-filled space around the brain, delayed the onset of inflammation and motor neuron degeneration by six months

Dr.

Dr Schneider said: "This study is an example of precision medicine, a bed-to-bed effort

Treatment began more than 6 months after clinical onset, by which time the disease had significantly worsened

By studying patients' brain and spinal cord tissue, the researchers found that the drug silenced FUS throughout the nervous system and reversed the toxicity of FUS and other disease-related proteins

FUS has been shown to be important in various cellular processes

Korobeynikov, VA, et al.