Methods and compositions for enhancing functional myelin production
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12612636-B2
Publication Date
2026-04-28
Expiration Date
Abstract
A method of generating a cell that enhances functional myelin production is provided, the method including genetically modifying the cell such that: (i) an endogenous PLP1 gene is modified to decrease its ability to inhibit myelin production; (ii) an endogenous PLP1 genetic regulatory element is modified to decrease its ability to promote PLP1 expression; (iii) an endogenous PLP1 genetic regulatory element is modified to increase its ability to inhibit PLP1 expression; or (iv) an endogenous PLP1 gene product or a PLP1 regulatory element gene product that promotes PLP1 expression is modified to decrease the PLP1 expression level, wherein the cell produces functional myelin.
Core Innovation
The invention provides methods for restoring functional myelin production in a cell in a subject with insufficient myelination. The methods involve delivering an RNAi construct, or a polynucleotide encoding the RNAi construct, to decrease the expression level of an endogenous PLP1 gene, wherein the endogenous PLP1 gene is a deleterious-disease causing mutant PLP1 gene.
The invention further provides a treatment approach for a myelin related disorder in a subject with insufficient myelination. The method includes administering an RNAi construct, or a polynucleotide encoding the RNAi construct, to decrease expression of an endogenous mutant PLP1 gene of a myelin-producing cell in the subject, thereby sufficiently restoring production of functional myelin in the subject.
The disclosed framework includes RNA interference modalities such as siRNA, shRNA, or miRNA, and delivery vehicles including lipid-based carriers and viral delivery concepts such as AAV, adenoviral, and lentiviral vectors. The approach is applied to differentiated progeny of the target myelin-producing cells, including neural stem cells, oligodendrocyte progenitor cells, and oligodendrocytes, with Pelizaeus-Merzbacher disease (PMD) given as an example disease context.
Claims Coverage
The partial content includes two independent claims. Across these claims, the inventive subject matter centers on RNAi-mediated reduction of endogenous mutant PLP1 expression to restore functional myelin production, with claim-dependent refinements for cell-based restoration, treatment of myelin-related disorders, RNAi type, delivery vehicle, target cell types, and PMD context.
RNAi-mediated decrease of endogenous mutant PLP1 to restore functional myelin
Delivering to a cell in a subject an RNAi construct, or a polynucleotide encoding said RNAi construct, to decrease expression level of an endogenous PLP1 gene, thereby sufficiently restoring functional myelin production by the cell, or by a differentiated progeny of the cell, wherein the endogenous PLP1 gene is a deleterious-disease causing mutant PLP1 gene.
RNAi-mediated decrease of endogenous mutant PLP1 in myelin-producing cells to treat myelin-related disorders
Administering to the subject an RNAi construct or a polynucleotide encoding said RNAi construct, to decrease expression level of an endogenous mutant PLP1 gene of a myelin-producing cell in the subject, thereby sufficiently restoring production of functional myelin in the subject, wherein the myelin related disorder is characterized by misfolded PLP1 protein or abnormal myelination caused by the endogenous mutant PLP1 gene.
Both independent claims are directed to sufficiently restoring functional myelin production by decreasing expression of an endogenous mutant PLP1 gene using an RNAi construct or an encoding polynucleotide. One claim is framed as restoring functional myelin in a cell in a subject with insufficient myelination, and the other is framed as treating a myelin-related disorder defined by misfolded PLP1 protein or abnormal myelination caused by the endogenous mutant PLP1 gene.
Stated Advantages
Sufficiently restoring functional myelin production in a subject with insufficient myelination.
Sufficiently restoring production of functional myelin in the subject.
Treating a myelin related disorder characterized by misfolded PLP1 protein or abnormal myelination caused by an endogenous mutant PLP1 gene.
Documented Applications
Treatment of Pelizaeus-Merzbacher disease (PMD).
Treating insufficient myelination associated with Pelizaeus-Merzbacher disease (PMD).
Interested in licensing this patent?