Self-Assessment: Novel Therapeutic Approaches for ALS: From Bench to Bedside

Video Transcription

Video Summary

In the video, the speaker discusses targeted therapies for genetic amyotrophic lateral sclerosis (ALS). They mention that a drug called Rel-Dassertive, a Cox inhibitor, was tested in a clinical trial with 300 patients but did not show any improvement in muscle strengthening. However, it is unclear whether target engagement was tested for this drug. <br /><br />The speaker then focuses on the recent FDA approval of Tofersen for SOD1 ALS, which uses antisense oligonucleotides (ASOs) to reduce levels of the mutant SOD1 protein. The phase three VALOR trial showed a significant reduction in the biomarker neurofilament light chain, which is associated with disease progression. Ongoing clinical trials for gene targeted therapies for different genetic forms of ALS, including C9ORF72 and FUS mutations, are also highlighted. ASOs are considered a promising therapeutic approach, and there is interest in early intervention and preventative treatment trials. <br /><br />The challenges and considerations in using these therapies are discussed, such as potential side effects and the need for genetic testing to identify suitable candidates. The speaker emphasizes the importance of neurofilament light chain as a biomarker for disease progression and mentions the potential role of epigenetics in ALS. During the Q&A session, questions are addressed about combining multiple therapies, assessing target engagement, the toxicity of different antisense strands, and the use of larger-scale genetic testing. <br /><br />Overall, the video provides an overview of targeted therapies for genetic ALS, including recent developments and future directions in treatment. The importance of genetic testing in guiding treatment decisions is emphasized, and ongoing clinical trials and the potential for early intervention and preventative approaches are discussed.

Keywords

targeted therapies

genetic ALS

Rel-Dassertive

Cox inhibitor

clinical trial

neurofilament light chain

SOD1 ALS

antisense oligonucleotides

gene targeted therapies

early intervention

genetic testing

biomarker

epigenetics

Q&A session