Methods for measuring concentrations of biomolecules

Abstract

The present invention provides methods for measuring the absolute concentration of a biomolecule of interest in a subject. Such biomolecules may be implicated in one or more neurological and neurodegenerative diseases or disorders. Also provided is a method for determining whether a therapeutic agent affects the in vivo metabolism of a central nervous system derived biomolecule. Also provided are kits for performing the methods of the invention.

What is claimed is: 
     
         1 . A kit for diagnosing or monitoring the progression or treatment of a neurological or neurodegenerative disease in a subject, the kit comprising:
 (a) one or more labeled amino acids;   (b) means for administering the one or more labeled amino acids to the subject, whereby the labeled amino acids are capable of incorporating into and labeling a biomolecule of interest in the subject;   (c) means for obtaining a biological sample at regular time intervals from the subject, wherein the sample comprises a labeled biomolecule fraction and an unlabeled biomolecule fraction;   (d) instructions for detecting and determining the ratio of labeled to unlabeled biomolecules of interest over time and for calculating the concentration of the unlabeled biomolecule in the sample, whereby the concentration of unlabeled biomolecule may be compared to the concentration of the same biomolecule in a corresponding normal sample, to the concentration of the same biomolecule in a subject of known neurological or neurodegenerative disease state, to the concentration of the same biomolecule from the same subject determined at an earlier time, or any combination thereof.   
     
     
         2 . The kit of  claim 1 , wherein the labeled amino acid is an essential amino acid. 
     
     
         3 . The kit of  claim 1 , wherein the labeled amino acid comprises a non-radioactive atom. 
     
     
         4 . The kit of  claim 3 , wherein the non-radioactive atom is selected from the group consisting of  2 H,  13 C,  15 N,  17 O,  18 O,  33 S,  34 S, and  36 S. 
     
     
         5 . The kit of  claim 1 , wherein the biomolecule is selected from the group consisting of a peptide, a lipid, a nucleic acid, and a carbohydrate. 
     
     
         6 . The kit of  claim 5 , wherein the biomolecule is a peptide that is synthesized in the central nervous system (CNS). 
     
     
         7 . The kit of  claim 1 , wherein the neurological or neurodegenerative disease is selected from the group consisting of Alzheimer's Disease, Parkinson's Disease, stroke, frontal temporal dementias (FTDs), Huntington's Disease, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), aging-related disorders and dementias, Multiple Sclerosis, Prion Diseases, Lewy Body Disease, Pick's Disease, motor neuron diseases, restless leg syndrome, seizure disorders, tremors, depression, mania, anxiety disorders, brain trauma or injury, narcolepsy, sleep disorders, autism, normal pressure hydrocephalus, pain disorders or syndromes, migraines, headaches, spinocerebellar disorders, muscular dystrophies, myasthenia gravis, retinal degeneration, and Amyotrophic Lateral Sclerosis.