Methods for diagnosing motor neuron diseases
AssigneeSwansea University
InventorsWilliam Griffiths, Peter Crick, Yuqin Wang, Jens Kuhle, Andreas Sailer, Juan Zhang, Martin Turner
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Abstract
The invention relates to methods for determining whether a subject is afflicted with a motor neuron disease, the method comprising conducting an analysis of cerebrospinal fluid and/or plasma, measuring the level of one or more sterol/oxysterol analytes, and comparing these to reference values. Further, the invention relates to methods of identifying agents suitable for the treatment of MND, and monitoring the progress of the disease.
Claims19
A method for determining whether a subject suspected of having amyotrophic lateral sclerosis (ALS) is afflicted with ALS, the method comprising:
- (a) obtaining a sample of a supernatant from centrifuged cerebrospinal fluid from the subject;
- (b) subjecting the sample to analysis to determine the concentration in the sample of at least one of a steroid selected from cholesterol (1), desmosterol (2), or combinations thereof, and optionally an additional oxysterol;
- (c) comparing the concentration of the at least one steroid present in the sample to a reference value of the at least one steroid obtained from a control population consisting of individuals not afflicted with ALS;
- and
- (d) diagnosing the subject as afflicted with ALS if the concentration of the at least one steroid from the subject is greater than the reference value.
A method of identifying an agent for the treatment of ALS, the method comprising:
- (a) administering a candidate agent to a non-human mammal model of ALS;
- (b) obtaining a sample of a supernatant from centrifuged cerebrospinal fluid from the non-human mammal;
- (c) subjecting the sample to analysis to determine the concentration in the sample of at least one of a steroid selected from cholesterol (1), desmosterol (2), or combinations thereof, and optionally an additional oxysterol;
- (d) comparing the concentration of the at least one steroid present in the sample to a reference value of the at least one steroid obtained from a control population consisting of individuals not afflicted with ALS;
- and
- (e) identifying the candidate agent as an agent for the treatment of ALS if the concentration of the at least one steroid from the subject is decreased compared to the value prior to administration.
A method for determining the responsiveness of a subject having amyotrophic lateral sclerosis (ALS) to treatment with at least one ALS therapy, the method comprising
- (a) administering the at least one ALS therapy to a subject having ALS;
- (b) obtaining a sample of a supernatant from centrifuged cerebrospinal fluid from the subject;
- (c) subjecting the sample to analysis to determine the concentration in the sample of at least one of a steroid selected from cholesterol (1), desmosterol (2), or combinations thereof, and optionally an additional oxysterol;
- (d) comparing the concentration of the at least one steroid present in the sample to the level of the same steroid or steroids prior to administration of the therapy;
- wherein an increase in the concentration of the at least one steroid is indicative that the subject is responsive or is likely to respond to the therapy.
A method of identifying a subject having amyotrophic lateral sclerosis (ALS) as suitable for treatment with at least one ALS therapy comprising the steps of
- (a) obtaining a sample of a supernatant from centrifuged cerebrospinal fluid from the subject;
- (b) subjecting the sample to analysis to determine the concentration in the sample of at least one of a steroid selected from cholesterol (1), desmosterol (2), or combinations thereof, and optionally an additional oxysterol;
- (c) comparing the concentration of the at least one steroid present in the sample to a reference value of the at least one steroid obtained from a control population consisting of individuals not afflicted with ALS;
- and
- (d) diagnosing the subject as suitable for treatment with the therapy if the concentration of the at least one steroid from the subject is greater than the reference value.
Dependencies are inferred from the claim text.