Exploiting epigenetics for the treatment of inborn errors of metabolism

Rutten, Martijn G. S.; Rots, Marianne G.; Oosterveer, Maaike H.

doi:10.1002/jimd.12093

Cited by 19 publications

(9 citation statements)

References 48 publications

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“…However, to the best of our knowledge, no studies on this field has been performed for GM2 gangliosidoses. The understanding of the epigenetic alterations observed in GM2 gangliosidoses patients may represent an opportunity to the develop of novel treatment alternatives [ 177 ].…”

Section: Discussionmentioning

confidence: 99%

GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies

Leal

Benincore-Flórez

Solano-Galarza

et al. 2020

IJMS

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GM2 gangliosidoses are a group of pathologies characterized by GM2 ganglioside accumulation into the lysosome due to mutations on the genes encoding for the β-hexosaminidases subunits or the GM2 activator protein. Three GM2 gangliosidoses have been described: Tay–Sachs disease, Sandhoff disease, and the AB variant. Central nervous system dysfunction is the main characteristic of GM2 gangliosidoses patients that include neurodevelopment alterations, neuroinflammation, and neuronal apoptosis. Currently, there is not approved therapy for GM2 gangliosidoses, but different therapeutic strategies have been studied including hematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction therapy, pharmacological chaperones, and gene therapy. The blood–brain barrier represents a challenge for the development of therapeutic agents for these disorders. In this sense, alternative routes of administration (e.g., intrathecal or intracerebroventricular) have been evaluated, as well as the design of fusion peptides that allow the protein transport from the brain capillaries to the central nervous system. In this review, we outline the current knowledge about clinical and physiopathological findings of GM2 gangliosidoses, as well as the ongoing proposals to overcome some limitations of the traditional alternatives by using novel strategies such as molecular Trojan horses or advanced tools of genome editing.

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Section: Discussionmentioning

confidence: 99%

GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies

Leal

Benincore-Flórez

Solano-Galarza

et al. 2020

IJMS

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show abstract

“…However, to the best of our knowledge, no studies on this field has been performed for GM2 gangliosidosis. The understanding of the epigenetic alterations observed in GM2 gangliosidosis patients may represent an opportunity to the develop of novel treatment alternatives [201].…”

Section: Discussionmentioning

confidence: 99%

GM2 Gangliosidosis: Clinical Features and Current Therapies

Leal¹,

Benincore-Flórez²,

Solano-Galarza³

et al. 2020

Preprint

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GM2 gangliosidosis are a group of pathologies characterized by GM2 ganglioside accumulation into the lysosome due to mutations on the genes encoding for the β-hexosaminidases subunits or the GM2 activator protein. Three GM2 gangliosidosis have been described: Tay-Sachs disease, Sandhoff disease, and AB variant. Central nervous system dysfunction is the main characteristic of GM2 gangliosidosis patients that include neurodevelopment alterations, neuroinflammation, and neuronal apoptosis. Currently, there is not approved therapy for GM2 gangliosidosis, but different therapeutic strategies have been studied including hematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction therapy, pharmacological chaperones, and gene therapy. The blood-brain barrier represents a challenge for the development of therapeutic agents for these disorders. In this sense, alternative routes of administration (e.g. intrathecal or intracerebroventricular) have been evaluated, as well as the design of fusion peptides that allow the protein transport from the brain capillaries to the central nervous system. In this review, we outline the current knowledge about clinical and physiopathological findings of GM2 gangliosidosis, as well as the ongoing proposals to overcome some limitations of the traditional alternatives by using novel strategies such as molecular Trojan horses or advanced tools of genome editing.

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“…Gene therapy and gene correction techniques aim to permanently compensate for the primary genetic defect [ 49 , 50 ]. In conventional gene therapy, this is achieved by providing patients with the correct coding DNA (cDNA) sequence of the defective gene leading to the expression of normal protein [ 50 , 51 ]. Delivery is accomplished by the use of vectors, either viral or non-viral, containing the genetic sequence of the protein [ 49 , 52 , 53 ].…”

Section: Potential Therapiesmentioning

confidence: 99%

Current and Future Treatments for Classic Galactosemia

Delnoy

Coelho

Rubio‐Gozalbo

2021

JPM

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Type I (classic) galactosemia, galactose 1-phosphate uridylyltransferase (GALT)-deficiency is a hereditary disorder of galactose metabolism. The current therapeutic standard of care, a galactose-restricted diet, is effective in treating neonatal complications but is inadequate in preventing burdensome complications. The development of several animal models of classic galactosemia that (partly) mimic the biochemical and clinical phenotypes and the resolution of the crystal structure of GALT have provided important insights; however, precise pathophysiology remains to be elucidated. Novel therapeutic approaches currently being explored focus on several of the pathogenic factors that have been described, aiming to (i) restore GALT activity, (ii) influence the cascade of events and (iii) address the clinical picture. This review attempts to provide an overview on the latest advancements in therapy approaches.

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Exploiting epigenetics for the treatment of inborn errors of metabolism

Cited by 19 publications

References 48 publications

GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies

GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies

GM2 Gangliosidosis: Clinical Features and Current Therapies

Current and Future Treatments for Classic Galactosemia

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