Development of therapies for rare genetic disorders of GPX4: roadmap and opportunities

Table 3 Short-listed repurposed treatments for SSMD and GPX4-related diseases

Name	Rationale	Availability	SSMD Status
Vitamin E	Potent antioxidant known to prevent ferroptosis	Over-the-counter	Administered to 2 of 4 patients Dosage: 15 mg 2X/day
N-Acetyl-Cysteine (NAC)	Increases glutathione biosynthesis to boost residual GPX4 activity	Over-the-counter	Administered to 2 of 4 patients Dosage: 300 mg 3X/day
CoQ10	Essential for repair of peroxidized lipids. Acts as an antioxidant	Over-the-counter	Administered to 2 of 4 patients Dosage: 50 mg 2X/day
Selenium	Limiting step in GPX4 production, may increase selenoprotein expression	Over-the-counter	Administered to 1 of 4 patients Dosage: 75 µg 1X/day
L-methionine	Increases glutathione biosynthesis through transsulferation pathway to boost residual GPX4 activity	Over-the-counter	Pending administration
RT001	Protects lipid membranes against peroxidation	In clinical trials for treating multiple indications	Administered to 2 of 4 patients under Expanded Access
Dimethyl fumarate	Activates Nrf2 gene, master regulator oxidative stress response	Approved in USA for treating multiple sclerosis	Evaluating for of off-label use

Collection of potential and in-use repurposed treatments for current SSMD patients

ISSN: 1750-1172