Patent Application: US-30508807-A

Abstract:
in vitro multiparameter method for the diagnosis and early diagnosis , for determination of the severity and for assessing the course and prognosis of neurodegenerative disorders , in which the concentrations of at least two different vasotropic peptides are determined in a biological fluid from a person suffering from subjective or objectively detectable cognitive impairments , the resulting person - specific measurements are combined computationally to give a person - specific complex reference value , and conclusions are drawn concerning the presence of a neurodegenerative disorder in the person on the basis of the person - specific complex reference value found .

Description:
the measurement of mr - proanp in plasma was effected using an immunoluminometric sandwich assay substantially as described in the experimental section of the abovementioned wo 2004 / 046181 ( copending u . s . application ser . no . 10 / 535 , 875 ), the contents of which are hereby incorporated by reference or in reference ( 12 ). the measurement of mr - proadm in plasma was effected using an immunoluminometric sandwich assay substantially as described in the experimental section of the abovementioned wo 2004 / 090546 ( copending u . s application ser . no . 10 / 551 , 298 the contents of which are hereby incorporated by reference or in reference ( 13 ). the measurement of ct - proet - 1 in plasma was effected using an immunoluminometric sandwich assay substantially as described in the experimental section of the above mentioned wo 2005 / 078456 ( copending u . s . application ser . no . 10 / 588 , 746 ), the contents of which are hereby incorporated by reference or reference ( 14 ). the measurement of mr - proanp , mr - proadm and ct - pro - et - 1 in the plasma of healthy controls and patients with cognitive disturbances of various severities for determining a reference value for the concentration of the respective analyte , a measurement was carried out in edta plasmas of 60 symptom - free control persons who neither showed symptoms of cognitive disturbances nor suffered from any other detectable disease ( cardiovascular diseases ; severe infection or inflammation ), for whom it is known that elevated levels of the abovementioned biomarker analytes can be measured in them . for the control group , median values were determined for the measured concentrations as follows : patients with dementia symptoms in the form of cognitive disturbances of various severities , on the basis of which an assignment of the individual patients to one of the abovementioned groups ( b ), ( c ) or ( d ) was made , served as a patient group . the measured mr - proanp , mr - proadm or ct - proet - 1 concentrations in the plasma of healthy controls and patients with cognitive disturbances are shown in fig1 to 3 . fig4 and 5 show the values which are obtained if the mr - proanp or mr - proadm concentrations are related to the associated ct - proet - 1 concentrations ( divided by the ct - proet - 1 concentrations ). the numerical values determined in the form of the so - called medians for the various patient groups are shown in table 1 . the specificities and sensitivities calculated from the measured values according to fig1 to 5 using the values stated in each case for the cut - off , in particular for the various patient groups , are shown in table 2 , in which the values obtained if the product of the concentrations for mr - proanp and those for mr - proadm is calculated ( mr - proanp × mr - proadm ) or if this product is additionally divided by the associated ct - proet - 1 concentrations were additionally recorded . the values in table 1 and in the corresponding figures show that in particular the mr - proanp concentrations , but also the mr - proadm concentrations , clearly increase with the severity of the symptoms in the direction : as is evident from the values for the medians of the various patient groups . it is furthermore evident that the trend , which is already recognizable in the individual determinations of mr - proanp or mr - proadm , is further illustrated if the measured values are divided by the associated ct - proet - 1 concentrations measured for the same patient in each case . table 2 shows that , in the determination of individual analytes , the highest sensitivity of 64 . 7 % is obtained in the determination of mr - proanp for the patient group “ probably alzheimer &# 39 ; s disease ” ( pr ad ) but that the sensitivity is further considerably improved and reaches a value of 80 . 8 % for the group “ pr ad ” if the measured values are related to the associated ct - proet - 1 concentrations . preliminary exploratory determinations of the concentrations of bnp ( using a commercial nt - probnp kit from roche diagnostics ) in the case of patients from the same patient groups and relation of the values obtained to the patient - specific measured values ( concentrations in pmol / l ) for ct - et - 1 by division gave similar improvements to those in the measurement of mr - proanp , i . e . the measured values for bnp , too , became more informative as a result of division by the ct - et - 1 concentrations . in the determination of mr - proadm , a similar improvement in the sensitivity is obtained ( 62 . 6 % compared with 50 . 5 %) in the case of a corresponding procedure . calculation of the product mr - proanp × mr - proadm results in no significant change compared with the values for the best individual analyte mr - proanp but in this case too , a clear improvement as above is obtained when said product is related to the measured values for the ct - proet - 1 concentrations . although increased release of vasotropic peptides , for example of anp , measured as mr - proanp concentration , or of adm , measured as mr - proadm , is measurable also in the case of other diseases ( sepsis , cardiovascular diseases / cardiac insufficiency ; however , these can as a rule be easily differentiated from dementias ) and vasotropic peptides are therefore not brain - specific parameters in the narrower sense , the determination of vasotropic peptides , in particular as a combination of the determination of vasodilatory peptides with a simultaneous determination of a suitable vasoconstrictive peptide , such as ct - pro - et - 1 , is very suitable for purposes of the diagnosis of dementias , in particular for supportive early ad diagnosis , on the basis of the high specificity and the clearly differentiatable sensitivities . 1 . selkoe d . j . 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