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. 2020 Mar 27;54(1):54-60.
doi: 10.1002/jmd2.12116. eCollection 2020 Jul.

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

Darius Adams  1 , Mark Midei  2 , Jahannaz Dastgir  1 , Christina Flora  1 , Robert J Molinari  2 , Frederic Heerinckx  2 , Sarah Endemann  2 , Paldeep Atwal  2 , Peter Milner  2 , Mikhail S Shchepinov  2
Affiliations

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

Darius Adams et al. JIMD Rep. .

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.

Keywords: INAD; NBIA; PLA2G6; PLAN; neurodegeneration.

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Conflict of interest statement

D. A., J. D., and C. F. declare no conflict of interest. P. M., F. H., M. M., P. A., and M. S., are employed by and holds stock in Retrotope. R. M. is a founder and holds stock in Retrotope, Inc. Sarah Endemann is employed by Retrotope. All authors confirm that the content of the article has not been influenced by the sponsor.

Figures

Figure 1
Figure 1
Plasma and RBC pharmacokinetic data for the two subjects is depicted graphically over time. Panel A, shows the ratio of plasma D2‐LA to total LA; Panel B, shows the ratio of RBC D2‐LA to total LA for the two subjects
Figure 2
Figure 2
Plasma and RBC pharmacokinetic data for the two subjects is depicted graphically over time. Panel A, shows the ratio of plasma D2‐AA to total AA; Panel B shows the ratio of RBC D2‐AA to total AA for the two subjects
Figure 3
Figure 3
Radar plots of the milestone category scoring for the two subjects. Panel A, depicts Subject #1 at maximal follow‐up of 1 year, and Panel B depicts Subject 2 at maximal follow‐up of 6 months
See this image and copyright information in PMC

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