Extracellular DNA as a therapeutic target in neurodegeneration
Inventors
Genkin, Dmitry Dmitrievich • Tets, Georgy Viktorovich • Tets, Viktor Veniaminovich
Assignees
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Publication Number
US-11701410-B2
Publication Date
2023-07-18
Expiration Date
Abstract
The invention relates to the use of deoxyribonuclease (DNase) enzyme for inhibiting progression and for prevention and treatment of neurodegeneration.
Core Innovation
The patent describes DNase-based therapy for primary neurodegeneration by targeting increased extracellular cell-free DNA. The neurodegeneration is associated with an increased level of extracellular DNA of prokaryotic origin in blood or cerebrospinal fluid or intestine, and extracellular DNA can penetrate the blood-brain barrier and is associated with neuronal toxicity and neurodegeneration.
The core therapeutic concept is administering a therapeutically effective amount of a DNase enzyme sufficient to decrease the average molecular weight of the extracellular DNA of prokaryotic origin. The patent further describes DNase embodiments including DNase I, recombinant DNase, and DNase I analogs, with an emphasis on reducing extracellular DNA levels and ameliorating disease symptoms.
To support treatment durability and delivery, the patent describes DNase formulations and modified DNase forms for extended half-life, including polysialation with polysialic acid and protection from binding to actin through modification of an actin binding site. It also describes potential delivery concepts to the central nervous system, including administration routes such as intravenous, subcutaneous, intramuscular, enteral/oral, and delivery into cerebrospinal fluid.
Claims Coverage
The independent claim covers a therapeutic method for primary neurodegeneration using a DNase enzyme targeted to patients with elevated extracellular prokaryotic-origin DNA in blood, cerebrospinal fluid, or intestine. The claim is centered on a molecular-weight endpoint and is refined by multiple dependent claims specifying DNA comparison, DNase type, route, dosing/duration, assay readout, and particular administration into cerebrospinal fluid.
Dnase treatment for primary neurodegeneration linked to extracellular prokaryotic DNA
A method for treating and/or inhibiting progression of primary neurodegeneration in a patient in need thereof by administering a therapeutically effective amount of a DNase enzyme to a patient whose neurodegeneration is associated with an increased level of extracellular DNA of prokaryotic origin in blood or cerebrospinal fluid or intestine.
Molecular weight reduction of extracellular prokaryotic DNA as therapeutic endpoint
The therapeutically effective amount of the DNase enzyme is sufficient to decrease the average molecular weight of said extracellular DNA of prokaryotic origin.
Overall, the claim coverage is anchored in administering DNase to patients with primary neurodegeneration associated with increased extracellular prokaryotic-origin DNA in blood, cerebrospinal fluid, or intestine, where the therapeutically effective amount decreases the average molecular weight of that extracellular DNA. Dependent claims further specify DNase type, administration route, quantitative dosing/duration thresholds, and gel electrophoresis as a molecular-weight measurement.
Stated Advantages
Decreases the average molecular weight of extracellular DNA of prokaryotic origin.
Reduces extracellular DNA levels and ameliorates disease symptoms.
Documented Applications
Treatment and/or inhibition of progression of primary neurodegeneration in patients associated with increased extracellular prokaryotic-origin DNA in blood or cerebrospinal fluid or intestine.
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