siRNA is expected to treat ALS gradual freezing

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, commonly known as gradual freezing disease.

Most cases of ALS are sporadic, and the cause is still not fully understood.

On May 31, 2021, researchers from the National Institutes of Health, Bethesda University of Health Sciences Uniform Service and other units published a report entitled: Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis in the top international medical journal Nature Medicine.

The report found that children with severe early-onset amyotrophic lateral sclerosis (ALS) have a rare mutation in the SPTLC1 gene, which encodes a key metabolic molecule responsible for the production of a class of sphingolipids.

This report reveals a single disease-causing gene for early-onset ALS, as well as a new metabolic-related molecular pathway, or cause neurodegeneration in other types of the disease.

Carsten Bönnemann of the Uniformed Service University of Health Sciences in Bethesda, Maryland, USA, and others sequenced the genomes of 9 patients from 7 families with severe early-onset ALS.

The authors found a set of rare mutations in a single gene (SPTLC1), which encodes a component of an enzyme involved in lipid metabolism.

SPTLC1 variants in children with ALS

This clinical study not only describes a set of rare single-gene mutations behind an aggressive early-onset ALS, but also shows that direct metabolic disorders are a pathogenic factor in the progression of the disease.

　　In addition, the research team also used siRNA for experiments to try to suppress the newly discovered mutant SPLTC1 gene.

　　These preliminary results indicate that precise gene silencing strategies can be used to treat patients with this type of frostbite.