The ever-growing group of white matter disorders also termed leukodystrophies, comprises neurogenetic diseases associated with an early onset, a high mortality rate, and the lack of treatment.
Leukodystrophies are heritable myelin diseases resulting in motor impairment, spasticity, ataxia, seizures, and delayed achievement of developmental milestones.
Individual leukodystrophies are rare but epidemiological data indicate a total population incidence of one in 7,600 births. The monogenic nature of many of these white matter disorders makes them amenable to somatic gene therapies, which hold great promise for permanent relief from the detrimental symptoms associated with this type of diseases.
While many white matter disorders are known to be caused primarily by mutations of genes that encode proteins important for oligodendrocyte function and hence directly impair myelin production or maintenance, myelin dysfunction can also be secondary to cellular or metabolic pathologies of astroglia or neurons reflecting abnormal glia-neuronal interactions. Gene therapy employing the ex vivo approach has shown remarkable clinical success for X-linked adrenoleukodystrophy (X-ALD) and metachromatic leukodystrophy (MLD). Gene therapy directed at transducing oligodendrocytes by somatic gene transfer in vivo has been notoriously difficult amid the lack of efficient gene delivery systems for glia.
Although many of the gene therapy approaches have led to clinical trials, expectations in the success of these trials have not yet been met. Therefore, more research is needed into this interesting topic at the crossing-lines of myelin biology and gene therapy.
This Research Topic brings together the fields of myelin biology and gene therapy.
Contributions from both fields ranging from the generation of novel genetic cell and animal models amenable to cell and gene therapy, to the development of experimental gene therapy strategies for white matter disorders, will be welcome, as well as regenerative approaches stimulating the endogenous self-repair mechanisms entailing differentiation and survival of oligodendrocyte precursors.
Both original research and review articles summarizing the progress of the field in recent years will be accepted.
This Topic will help us bring together the two fields of science and let them meet at the cross-roads of myelin biology and gene therapy to pave a new path forward.
Topic Editors Dr Matthias Klugmann and Dr Dominic Gessler are affiliated with Research Beyond Borders, Boehringer-Ingelheim GmbH & Co KG, and ASPA Therapeutics, Inc., respectively. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
The ever-growing group of white matter disorders also termed leukodystrophies, comprises neurogenetic diseases associated with an early onset, a high mortality rate, and the lack of treatment.
Leukodystrophies are heritable myelin diseases resulting in motor impairment, spasticity, ataxia, seizures, and delayed achievement of developmental milestones.
Individual leukodystrophies are rare but epidemiological data indicate a total population incidence of one in 7,600 births. The monogenic nature of many of these white matter disorders makes them amenable to somatic gene therapies, which hold great promise for permanent relief from the detrimental symptoms associated with this type of diseases.
While many white matter disorders are known to be caused primarily by mutations of genes that encode proteins important for oligodendrocyte function and hence directly impair myelin production or maintenance, myelin dysfunction can also be secondary to cellular or metabolic pathologies of astroglia or neurons reflecting abnormal glia-neuronal interactions. Gene therapy employing the ex vivo approach has shown remarkable clinical success for X-linked adrenoleukodystrophy (X-ALD) and metachromatic leukodystrophy (MLD). Gene therapy directed at transducing oligodendrocytes by somatic gene transfer in vivo has been notoriously difficult amid the lack of efficient gene delivery systems for glia.
Although many of the gene therapy approaches have led to clinical trials, expectations in the success of these trials have not yet been met. Therefore, more research is needed into this interesting topic at the crossing-lines of myelin biology and gene therapy.
This Research Topic brings together the fields of myelin biology and gene therapy.
Contributions from both fields ranging from the generation of novel genetic cell and animal models amenable to cell and gene therapy, to the development of experimental gene therapy strategies for white matter disorders, will be welcome, as well as regenerative approaches stimulating the endogenous self-repair mechanisms entailing differentiation and survival of oligodendrocyte precursors.
Both original research and review articles summarizing the progress of the field in recent years will be accepted.
This Topic will help us bring together the two fields of science and let them meet at the cross-roads of myelin biology and gene therapy to pave a new path forward.
Topic Editors Dr Matthias Klugmann and Dr Dominic Gessler are affiliated with Research Beyond Borders, Boehringer-Ingelheim GmbH & Co KG, and ASPA Therapeutics, Inc., respectively. All other Topic Editors declare no competing interests with regards to the Research Topic subject.