Treatment of infantile neuroaxonal dystrophy with RT001: A di‐deuterated ethyl ester of linoleic acid: Report of two cases

Background Infantile neuroaxonal dystrophy (INAD) is a rare, autosomal recessive disease due to defects in PLA2G6 and is associated with lipid peroxidation. RT001 is a di‐deuterated form of linoleic acid that protects lipids from oxidative damage. Methods We evaluated the pharmacokinetics (PK), safe...

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Published inJIMD reports Vol. 54; no. 1; pp. 54 - 60
Main Authors Adams, Darius, Midei, Mark, Dastgir, Jahannaz, Flora, Christina, Molinari, Robert J, Heerinckx, Frederic, Endemann, Sarah, Atwal, Paldeep, Milner, Peter, Shchepinov, Mikhail S.
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.07.2020
Wiley
Subjects
Clinical trials
Dietary supplements
Disease
INAD
Lipid peroxidation
Lipids
Membranes
NBIA
neurodegeneration
Oxidative stress
Pharmacokinetics
PLA2G6
PLAN
Plasma
Research Report
Research Reports
NBIA
neurodegeneration
INAD
PLA2G6
PLAN
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Summary:Background Infantile neuroaxonal dystrophy (INAD) is a rare, autosomal recessive disease due to defects in PLA2G6 and is associated with lipid peroxidation. RT001 is a di‐deuterated form of linoleic acid that protects lipids from oxidative damage. Methods We evaluated the pharmacokinetics (PK), safety, and effectiveness of RT001 in two subjects with INAD (subject 1: 34 months; subject 2: 10 months). After screening and baseline evaluations, subjects received 1.8 g of RT001 BD. PK analysis and clinical evaluations were made periodically. Main findings Plasma levels of deuterated linoleic acid (D2‐LA), deuterated arachidonic acid (D2‐AA), D2‐LA to total LA, and D2‐AA to total AA ratios were measured. The targeted plasma D2‐LA ratio (>20%) was achieved by month 1 and maintained throughout the study. RBC AA‐ratios were 0.11 and 0.18 at 6 months for subjects 1 and 2; respectively. No treatment‐related adverse events occurred. Limited slowing of disease progression and some return of lost developmental milestones were seen. Conclusions Oral RT001 was administered safely in two subjects with INAD. Early findings suggest that the compound was well tolerated, metabolized and incorporated in the RBC membrane. A clinical trial is underway to assess efficacy.
Bibliography:Funding information
Retrotope
Funding information Retrotope
Communicating Editor: Areeg El‐Gharbawy
ISSN:2192-8312
2192-8304
2192-8312
DOI:10.1002/jmd2.12116