Combinatorial treatment for amyotrophic lateral sclerosis (ALS)

Unmet Need: Therapeutics for targeting gene dysregulation in ALS patients with SOD1 mutation

Amyotrophic lateral sclerosis (ALS) patients with SOD1 mutations can be treated with Tofersen (Qalsody), an antisense oligonucleotide (ASO) therapy to reduce the production of toxic mutant SOD1 proteins by targeting SOD1 mRNA. However, in a Phase III trial, Tofersen did not improve clinical end points and was associated with adverse events. Generalized ALS treatments, such as Riluzole (Rilutek) and Edaravone (Radicava), provide modest benefits by slowing disease progression, but there are currently no therapeutics that directly target gene dysregulation, leaving a gap for early intervention.

The Technology: Combinatorial antisense oligonucleotide (ASO) treatment for targeting dysregulated genes in SOD1-ALS

This technology identifies a set of 15 genes that are dysregulated in motor neurons at early stages of amyotrophic lateral sclerosis (ALS) with SOD1 mutation and can serve as therapeutic targets. By injecting SOD1-G93 ALS mice with antisense oligonucleotides (ASOs) at birth, the expression levels of dysregulated genes can be corrected, resulting in minimized motor neuron death and improved physical capacity. This technology addresses the complex nature of SOD1-ALS by targeting multiple genes simultaneously.

This technology has been validated in SOD1-G931 ALS mouse models.

Applications:

Targeted combinatorial therapeutics for amyotrophic lateral sclerosis (ALS) with SOD1 mutation
Generalized treatment strategy for ALS
ALS biomarker discovery and validation
ASO screening platform
Human iPSC-based disease modeling

Advantages:

Targets dysregulation of multiple genes simultaneously
Enhances behavior of ALS-SOD1 mice
Minimizes neuron death

Lead Inventor:

George Mentis, Ph.D.

JoonHyung Park, Ph.D.

Patent Information:

Related Publications:

Tech Ventures Reference:

IR CU25447
Licensing Contact: Jerry Kokoshka