SOD1-lowering therapy for patients with wildtype SOD1-ALS: a case report

Area of Science:

• Neurology
• Genetics
• Molecular Biology

Background:

• Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease.
• Mutations in the SOD1 gene are a known cause of familial ALS.
• This study focuses on a patient with non-SOD1 ALS.

Purpose of the Study:

• To describe the clinical and biomarker experience of using an SOD1 antisense oligonucleotide (ASO) in a patient with non-SOD1 ALS.
• To evaluate the potential therapeutic effect of SOD1 ASO in this specific patient profile.

Main Methods:

• Case report methodology.
• Administration of 3 loading doses of an SOD1 ASO.
• Monitoring of ALS Functional Rating Scale-Revised (ALSFRS-R) scores.
• Measurement of serum neurofilament light chain (NfL) concentration.

Main Results:

• A 72-year-old male with non-SOD1 ALS experienced rapid functional decline (ALSFRS-R).
• Serum NfL concentration increased after SOD1 ASO administration.
• The patient succumbed to the disease 9 months after symptom onset.
• Treatment was initiated approximately 7 months after symptom onset with a short follow-up duration.

Conclusions:

• The observed increase in serum NfL and rapid functional decline suggest a lack of therapeutic effect from SOD1 ASO in this patient.
• Late treatment initiation and rapid disease progression may have influenced the outcome.
• Further research is needed to understand the efficacy of SOD1 ASO in non-SOD1 ALS subtypes.