Methods of treating neurological disorders
Inventors
Navia, Manuel A. • Roet, Kasper • Fleming, Jonathan
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11419921-B2
Publication Date
2022-08-23
Expiration Date
Abstract
Disclosed is a method for treating a subject having a neurological disorder characterized by the presence of dipeptide repeat proteins comprising contacting the cerebrospinal fluid (CSF) of the subject with an agent capable of removing or degrading the toxic protein.
Core Innovation
The invention relates to treating a neurological disorder characterized by the presence of a dipeptide repeat protein in cerebrospinal fluid (CSF). The method comprises contacting the CSF of a subject in need thereof with an effective amount of a protease capable of removing the dipeptide repeat protein, where the dipeptide repeat protein comprises two or more repeats of a dipeptide amino acid sequence.
The neurological disorder is selected from amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In disclosed embodiments, the protease is proteinase K and is immobilized, including immobilization at a concentration of 1-10 milligrams per milliliter and immobilization on an agarose substrate.
The disclosed approach further characterizes protease behavior in CSF by requiring higher specificity and higher affinity to the dipeptide repeat protein compared to a plurality of other proteins occurring in the CSF. The invention also supports identifying suitable subjects by detecting the dipeptide repeat protein in the CSF, including embodiments where detection is conducted prior to contacting.
Claims Coverage
The independent claims cover treating ALS and/or FTD where dipeptide repeat proteins in CSF are removed by contacting CSF with immobilized proteinase K. The inventive features emphasize immobilization and protease concentration, agarose immobilization, and higher specificity and higher affinity to the dipeptide repeat protein compared to other CSF proteins.
Treating ALS or FTD by CSF contacting with immobilized proteinase K
A method of treating a neurological disorder characterized by the presence of a dipeptide repeat protein in cerebrospinal fluid (CSF) by contacting the CSF of a subject in need thereof with an effective amount of a protease capable of removing the dipeptide repeat protein, wherein the dipeptide repeat protein comprises two or more repeats of a dipeptide amino acid sequence, wherein the protease is proteinase K, and wherein the neurological disorder is selected from the group consisting of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Immobilized proteinase K on agarose substrate for CSF contacting
A method of treating a neurological disorder characterized by the presence of a dipeptide repeat protein in cerebrospinal fluid (CSF) by contacting the CSF of a subject in need thereof with an effective amount of a protease capable of removing the dipeptide repeat protein, wherein the dipeptide repeat protein comprises two or more repeats of a dipeptide amino acid sequence, wherein the neurological disorder is selected from the group consisting of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), wherein the protease is proteinase K and is immobilized to an agarose substrate.
Immobilized proteinase K with higher specificity and higher affinity in CSF
A method of treating a neurological disorder characterized by the presence of a dipeptide repeat protein in cerebrospinal fluid (CSF) by contacting the CSF of a subject in need thereof with an effective amount of a protease capable of removing the dipeptide repeat protein, wherein the dipeptide repeat protein comprises two or more repeats of a dipeptide amino acid sequence, wherein the protease is immobilized at a concentration of 1-10 milligrams per milliliter of the protease, wherein the neurological disorder is selected from the group consisting of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), wherein the protease is proteinase K and the protease has higher specificity and higher affinity to the dipeptide repeat protein compared to a plurality of other proteins occurring in the CSF.
The core claim coverage is directed to treating ALS and/or FTD by contacting CSF with an effective amount of proteinase K that is immobilized and capable of removing CSF dipeptide repeat proteins having two or more dipeptide repeats. The claims further differentiate embodiments by specifying immobilization concentration, agarose immobilization, and higher specificity and higher affinity to the dipeptide repeat protein compared to other CSF proteins.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?