Treatment of infantile neuroaxonal dystrophy with RT001: A di‐deuterated ethyl ester of linoleic acid: Report of two cases
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 (...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-07-01
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| Series: | JIMD Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jmd2.12116 |
| _version_ | 1818684598636249088 |
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| author | Darius Adams Mark Midei Jahannaz Dastgir Christina Flora Robert J Molinari Frederic Heerinckx Sarah Endemann Paldeep Atwal Peter Milner Mikhail S. Shchepinov |
| author_facet | Darius Adams Mark Midei Jahannaz Dastgir Christina Flora Robert J Molinari Frederic Heerinckx Sarah Endemann Paldeep Atwal Peter Milner Mikhail S. Shchepinov |
| author_sort | Darius Adams |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T10:53:11Z |
| format | Article |
| id | doaj.art-39110a888b0543f1bda4a330bf80b067 |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-12-17T10:53:11Z |
| publishDate | 2020-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-39110a888b0543f1bda4a330bf80b0672022-12-21T21:51:54ZengWileyJIMD Reports2192-83122020-07-01541546010.1002/jmd2.12116Treatment of infantile neuroaxonal dystrophy with RT001: A di‐deuterated ethyl ester of linoleic acid: Report of two casesDarius Adams0Mark Midei1Jahannaz Dastgir2Christina Flora3Robert J Molinari4Frederic Heerinckx5Sarah Endemann6Paldeep Atwal7Peter Milner8Mikhail S. Shchepinov9Atlantic Health System Goryeb Children's Hospital Morristown New Jersey USAClinical Division Retrotope, Inc. Los Altos California USAAtlantic Health System Goryeb Children's Hospital Morristown New Jersey USAAtlantic Health System Goryeb Children's Hospital Morristown New Jersey USAClinical Division Retrotope, Inc. Los Altos California USAClinical Division Retrotope, Inc. Los Altos California USAClinical Division Retrotope, Inc. Los Altos California USAClinical Division Retrotope, Inc. Los Altos California USAClinical Division Retrotope, Inc. Los Altos California USAClinical Division Retrotope, Inc. Los Altos California USAAbstract 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.https://doi.org/10.1002/jmd2.12116INADNBIAneurodegenerationPLA2G6PLAN |
| spellingShingle | Darius Adams Mark Midei Jahannaz Dastgir Christina Flora Robert J Molinari Frederic Heerinckx Sarah Endemann Paldeep Atwal Peter Milner Mikhail S. Shchepinov Treatment of infantile neuroaxonal dystrophy with RT001: A di‐deuterated ethyl ester of linoleic acid: Report of two cases JIMD Reports INAD NBIA neurodegeneration PLA2G6 PLAN |
| title | Treatment of infantile neuroaxonal dystrophy with RT001: A di‐deuterated ethyl ester of linoleic acid: Report of two cases |
| title_full | Treatment of infantile neuroaxonal dystrophy with RT001: A di‐deuterated ethyl ester of linoleic acid: Report of two cases |
| title_fullStr | Treatment of infantile neuroaxonal dystrophy with RT001: A di‐deuterated ethyl ester of linoleic acid: Report of two cases |
| title_full_unstemmed | Treatment of infantile neuroaxonal dystrophy with RT001: A di‐deuterated ethyl ester of linoleic acid: Report of two cases |
| title_short | Treatment of infantile neuroaxonal dystrophy with RT001: A di‐deuterated ethyl ester of linoleic acid: Report of two cases |
| title_sort | treatment of infantile neuroaxonal dystrophy with rt001 a di deuterated ethyl ester of linoleic acid report of two cases |
| topic | INAD NBIA neurodegeneration PLA2G6 PLAN |
| url | https://doi.org/10.1002/jmd2.12116 |
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