High Dose Pharmaceutical Grade Biotin (MD1003) Accelerates Differentiation of Murine and Grafted Human Oligodendrocyte Progenitor Cells In Vivo
Accumulating evidences suggest a strong correlation between metabolic changes and neurodegeneration in CNS demyelinating diseases such as multiple sclerosis (MS). Biotin, an essential cofactor for five carboxylases, is expressed by oligodendrocytes and involved in fatty acid synthesis and energy pro...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/15733 |
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| author | Marion J. F. Levy Beatriz Garcia-Diaz Frédéric Sedel Anne Baron-Van Evercooren Sabah Mozafari |
| author_facet | Marion J. F. Levy Beatriz Garcia-Diaz Frédéric Sedel Anne Baron-Van Evercooren Sabah Mozafari |
| author_sort | Marion J. F. Levy |
| collection | DOAJ |
| description | Accumulating evidences suggest a strong correlation between metabolic changes and neurodegeneration in CNS demyelinating diseases such as multiple sclerosis (MS). Biotin, an essential cofactor for five carboxylases, is expressed by oligodendrocytes and involved in fatty acid synthesis and energy production. The metabolic effect of biotin or high-dose-biotin (MD1003) has been reported on rodent oligodendrocytes in vitro, and in neurodegenerative or demyelinating animal models. However, clinical studies, showed mild or no beneficial effect of MD1003 in amyotrophic lateral sclerosis (ALS) or MS. Here, we took advantage of a mouse model of myelin deficiency to study the effects of MD1003 on the behavior of murine and grafted human oligodendrocytes in vivo. We show that MD1003 increases the number and the differentiation potential of endogenous murine oligodendroglia over time. Moreover, the levels of MD1003 are increased in the plasma and brain of pups born to treated mothers, indicating that MD1003 can pass through the mother’s milk. The histological analysis of the grafted animals shows that MD1003 increased proliferation and accelerates differentiation of human oligodendroglia, but without enhancing their myelination potential. These findings provide important insights into the role of MD1003 on murine and human oligodendrocyte maturation/myelination that may explain the mitigated outcome of ALS/MS clinical trials. |
| first_indexed | 2024-03-09T16:20:12Z |
| format | Article |
| id | doaj.art-e774ea7b67144dd4a0678dc4fc841c3c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:20:12Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e774ea7b67144dd4a0678dc4fc841c3c2023-11-24T15:27:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241573310.3390/ijms232415733High Dose Pharmaceutical Grade Biotin (MD1003) Accelerates Differentiation of Murine and Grafted Human Oligodendrocyte Progenitor Cells In VivoMarion J. F. Levy0Beatriz Garcia-Diaz1Frédéric Sedel2Anne Baron-Van Evercooren3Sabah Mozafari4INSERM, U1127, 75013 Paris, FranceINSERM, U1127, 75013 Paris, FranceMedDay Pharmaceuticals SA, 75008 Paris, FranceINSERM, U1127, 75013 Paris, FranceINSERM, U1127, 75013 Paris, FranceAccumulating evidences suggest a strong correlation between metabolic changes and neurodegeneration in CNS demyelinating diseases such as multiple sclerosis (MS). Biotin, an essential cofactor for five carboxylases, is expressed by oligodendrocytes and involved in fatty acid synthesis and energy production. The metabolic effect of biotin or high-dose-biotin (MD1003) has been reported on rodent oligodendrocytes in vitro, and in neurodegenerative or demyelinating animal models. However, clinical studies, showed mild or no beneficial effect of MD1003 in amyotrophic lateral sclerosis (ALS) or MS. Here, we took advantage of a mouse model of myelin deficiency to study the effects of MD1003 on the behavior of murine and grafted human oligodendrocytes in vivo. We show that MD1003 increases the number and the differentiation potential of endogenous murine oligodendroglia over time. Moreover, the levels of MD1003 are increased in the plasma and brain of pups born to treated mothers, indicating that MD1003 can pass through the mother’s milk. The histological analysis of the grafted animals shows that MD1003 increased proliferation and accelerates differentiation of human oligodendroglia, but without enhancing their myelination potential. These findings provide important insights into the role of MD1003 on murine and human oligodendrocyte maturation/myelination that may explain the mitigated outcome of ALS/MS clinical trials.https://www.mdpi.com/1422-0067/23/24/15733MD1003murine oligodendrocyteshuman oligodendrocyteshumanized animal modelshiverer miceoligodendrocyte differentiation |
| spellingShingle | Marion J. F. Levy Beatriz Garcia-Diaz Frédéric Sedel Anne Baron-Van Evercooren Sabah Mozafari High Dose Pharmaceutical Grade Biotin (MD1003) Accelerates Differentiation of Murine and Grafted Human Oligodendrocyte Progenitor Cells In Vivo International Journal of Molecular Sciences MD1003 murine oligodendrocytes human oligodendrocytes humanized animal model shiverer mice oligodendrocyte differentiation |
| title | High Dose Pharmaceutical Grade Biotin (MD1003) Accelerates Differentiation of Murine and Grafted Human Oligodendrocyte Progenitor Cells In Vivo |
| title_full | High Dose Pharmaceutical Grade Biotin (MD1003) Accelerates Differentiation of Murine and Grafted Human Oligodendrocyte Progenitor Cells In Vivo |
| title_fullStr | High Dose Pharmaceutical Grade Biotin (MD1003) Accelerates Differentiation of Murine and Grafted Human Oligodendrocyte Progenitor Cells In Vivo |
| title_full_unstemmed | High Dose Pharmaceutical Grade Biotin (MD1003) Accelerates Differentiation of Murine and Grafted Human Oligodendrocyte Progenitor Cells In Vivo |
| title_short | High Dose Pharmaceutical Grade Biotin (MD1003) Accelerates Differentiation of Murine and Grafted Human Oligodendrocyte Progenitor Cells In Vivo |
| title_sort | high dose pharmaceutical grade biotin md1003 accelerates differentiation of murine and grafted human oligodendrocyte progenitor cells in vivo |
| topic | MD1003 murine oligodendrocytes human oligodendrocytes humanized animal model shiverer mice oligodendrocyte differentiation |
| url | https://www.mdpi.com/1422-0067/23/24/15733 |
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