Treatment of infantile neuroaxonal dystrophy with RT001: A di-deuterated ethyl ester of linoleic acid: Report of two cases.
Darius J. Adams,Mark G. Midei,Jahannaz Dastgir,Christina Flora,Robert J. Molinari,Frederic Heerinckx,Sarah Endemann,Paldeep S. Atwal,Peter G. Milner,Mikhail S. Shchepinov +9 more
- Vol. 54, Iss: 1, pp 54-60
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TLDR
RT001 is a di‐deuterated form of linoleic acid that protects lipids from oxidative damage that is associated with lipid peroxidation in infantile neuroaxonal dystrophy.Abstract:
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.read more
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Journal ArticleDOI
Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA).
TL;DR: This review aims to describe the existing link between the classical ten NBIA forms by examining their connection with mitochondrial impairment as well as oxidative stress and neuroinflammation.
Journal ArticleDOI
Emerging Disease-Modifying Therapies in Neurodegeneration With Brain Iron Accumulation (NBIA) Disorders.
TL;DR: A recent review as mentioned in this paper discusses the rationale of new compounds, summarize results from clinical trials, provide an overview of important results in cell lines and animal models and discuss the future development of disease-modifying therapies for NBIA disorders.
Journal ArticleDOI
Plasma and red blood cell membrane accretion and pharmacokinetics of RT001 (bis-allylic 11,11-D2-linoleic acid ethyl ester) during long term dosing in patients
J. Thomas Brenna,Genevieve James,Mark G. Midei,Frederic Heerinckx,Paldeep S. Atwal,Peter Milner,Karsten Schmidt,Lex van der Ploeg,Robert Fielding,Mikhail S. Shchepinov +9 more
TL;DR: It is concluded that chronic dosing of RT001 and associated dietary guidance can be maintained over many months to achieve target plasma and RBC levels, forming a basis for therapeutic dosing across a broad range of conditions.
Journal ArticleDOI
Vitamin E prevents lipid peroxidation and iron accumulation in PLA2G6-Associated Neurodegeneration
TL;DR: In this paper , the effects of α-tocopherol (vitamin E) in correcting the pathophysiological alterations in PL2G6-associated neurodegeneration (PLAN) cell cultures were examined in fibroblasts and induced neurons generated by direct reprograming.
Journal ArticleDOI
Toward Quantitative Sequencing of Deuteration of Unsaturated Hydrocarbon Chains in Fatty Acids.
Dong Hao Wang,Hui Gyu Park,Zhen Wang,R.J. Scott Lacombe,Vadim V. Shmanai,Andrei V. Bekish,Karsten Schmidt,Mikhail S. Shchepinov,J. Thomas Brenna +8 more
TL;DR: In this article, the Paterno-Buchi reaction of 2-acetylpyridine was applied to a series of bis-allylic deuterated highly unsaturated fatty acids (D-HUFA) to determine position-specific quantitative deuterium abundances.
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