Diagnosis and monitoring of diseases

Abstract

The present invention relates to the diagnosis and monitoring of diseases and conditions by quantifying markers, including degradation products of disease-associated proteins, such as diketopiperazines composed of the two N-terminal amino acids or the two C-terminal amino acids of such proteins. The methods are useful for diagnosing or monitoring various diseases, including multiple sclerosis, Alzheimer's disease and ischemia. The invention further provides binding partners specific for the markers and compositions and kits for conducting the methods of the invention.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a Continuation of U.S. application Ser. No. 10 / 679,699, filed Oct. 2, 2003, which claims the benefit of U.S. Provisional Applications 60 / 415,908, filed Oct. 2, 2002, 60 / 489,039, filed Jul. 21, 2003, and 60 / 503,185, filed Sep. 15, 2003. The complete disclosures of these applications are incorporated herein by reference for all purposes.FIELD OF THE INVENTION[0002]The invention relates to the diagnosis and monitoring of diseases and medical conditions by quantitating one or more biochemical markers associated with the diseases or conditions. In particular, the invention relates to the detection and measurement of diketopiperazines composed of the two N-terminal amino acids of disease-associated proteins, diketopiperazines composed of the two C-terminal amino acids of disease-associated proteins, truncated disease-associated proteins missing the two N-terminal amino acids and / or the two C-terminal amino acids, and other b...

AI Technical Summary

Benefits of technology

[0026]Accordingly, the present invention provides a method of diagnosing or monitoring a disease or condition comprising determining the quantity of one or more target markers in a biological sample and determining if the quantity(ies) of the marker(s) is(are) indicative of the presence, absence or status of the disease or condition. The target markers can be measured rapidly and conveniently, and these measurements provide objective evidence which will allow a reliable diagnosis to be made easily and quickly for diseases and conditions, such as, for example, multiple sclerosis, Alzheimer' s disease and ischemia, particularly placental ischemia. This method will be of great benefit, since it will allow treatment of many diseases and conditions to begin much earlier than is now possible. In addition, the measurement of the target markers will allow the status of the diseases or conditions to be monitored, allowing for more effective treatment of many diseases, conditions and disorders and for the evaluation of new drugs and other treatments.

Problems solved by technology

In addition, many serious illnesses remain difficult to diagnose and monitor, and methods of diagnosing and monitoring these diseases and conditions are critically needed.

For instance, multiple sclerosis (MS) is difficult to diagnose because the progress, severity and specific symptoms of MS are quite variable and unpredictable.

1. There must be objective evidence of two attacks (i.e., two episodes of demyelination in the central nervous system (CNS)). An attack (also known as an exacerbation, flare or relapse) is defined clinically as the sudden appearance or worsening of an MS symptom or symptoms, which lasts at least 24 hours. The objective evidence comes from findings of a neurological examination and additional tests.

2. The two attacks must be separated in time (at least one month apart) and space (indicated by evidence of inflammation and / or damage in different areas of the CNS).

3. There must be no other explanation for these attacks or the symptoms the person is experiencing. Many symptoms that are common in MS can also be caused by other diseases. Therefore, the MS diagnosis can only be made by carefully ruling out all possibilities.

However, even with these revised criteria, diagnosis of MS is still difficult and still typically takes several months or even years.

The diagnosis of Alzheimer's disease is difficult and often relies on the exclusion of other causes.

However, a definitive diagnosis is only possible by a brain autopsy after death.

Early cardiac ischemia is also difficult to diagnose.

Low birth weight (LBW) is the leading cause of fetal and neonatal morbidity and mortality worldwide.

As such, the epidemiology of LBW is complex and multifactorial.

These infants are difficult to identify in a practical sense, as there is no a priori way of knowing how much an individual “should” weigh.

Via these various mechanisms, the disease burden attributable to FGR is tremendous.

Preeclampsia and its complications are the leading causes of maternal mortality worldwide.

In the clinical setting, although various risk factors for FGR are recognized, their positive predictive values and sensitivities are limited.

There can be difficulty differentiating the FGR fetus from the “SGA but well” fetus.

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