a blood protein marker for the early detection of pre- eclampsia

A BLOOD PROTEIN MARKER FOR THE EARLY DETECTION OF PRE- ECLAMPSIA

Helena Gwani

Ayotunde Awosusi

Daniel Igwe

Priyesh Waghmare

Srishti Jain

Vinie Varkey T

A G7 DIAGNOSTICS PRESENTATION

OUTLINE Pre- eclempsia: What is it?

Causes of maternal death

Global maternity mortality

Pre-eclempsia distribution

Current diagnosis

Market need

Product specifications

Conclusion

Pre- Eclampsia

Globally,

•10% of all pregnancies

•12% of maternal deaths

•1/3rd of pre mature births

Causes:

•Damage to the blood vessels

•Insufficient blood flow to the uterus

Symptoms:

•Rising High blood pressure

•High protein levels in the urine

•Severe headache

•Visual Disturbances

•Vomiting and abdominal pain

RISK FACTORS

Medical problems

First time pregnancy

Family history

Previous case of pre-eclampsia

40 years or older

Obesity

Multiple birth

Source: http://jalesknowsbabiesrock.blogspot.com/2010/10/annotated-webliography-of-preeclampsia.html

CAUSES OF MATERNAL DEATH

GLOBAL MATERNAL MORTALITY

PRE-ECLAMPSIA DISTRIBUTION (EXTRAPOLATED FIGURES)

Source: http://www.cureresearch.com/p/preeclampsia/stats-country.htm

CURRENT DIAGNOSISMethod Description Limitations

Blood pressure (>140/90) • Time consuming

•Complex

•Low reliability

•Late diagnosis

•Rate of false positive result is high.

Protein concentration in urine (>300mg/dL)

Blood tests: liver, kidneys, platelets number.

Uterine artery Doppler ultrasound

The ideal Screening test: Simple

Noninvasive

Rapid

Inexpensive

Early detection

Highly sensitivity & predictive

HOW CAN WE APPROACH THE PROBLEM?

MARKET NEED

12% of maternal deaths

Our market research reveals:

There is no clinically useful screening test to predict the development of preeclampsia in either low-risk or high-risk populations.

Global prevalence of pre-eclampsia

PRODUCT SPECIFICATIONS

Intended uses of the test: early detection pre-eclempsia

Target population/patient: Pregnant women (first trimester)

Health facility where the test will be used: clinics, health centers and hospitals

Biomarker:

A biological indicator whose presence, absence or abnormal concentration reflects the severity or presence of a disease.

S.No. Biochemical Marker Plasma ConcentrationTrimester 1 Trimester 2

Manifest Preeclampsia

1. sflt-1 (Soluble fms- like tyrosine kinase)

-- high Early increase

2. Soluble Endoglin (sEng)

-- high Early increase

3. Placental Growth Factor (PlGF)

low low further decrease

Sample Port

Reaction Chamber

A small fraction of the Plasma sample mixes

withthe dried reagents

Three Internal Controls

Independent Positive High –

and low – control zones and a nonspecific

binding control

Waste Reservoir

Excess sample collected in the

periphery

Blood FilterCells are

separated from plasma

TimegateHyrdrophobic surface –

ensures reaction time

Assay Zones

Fluoroscent tagged

antibodies on nano

particles are captured on

separate zones

G7 PRE-ECLAMPSIA DIAGNOSTIC DEVICE

PRIORITY FEATURES

Target molecule •Placental Growth Factor(PlGF), •Soluble Isoforms of flt-1 (sflt-1), •Soluble Endoglin (sEng)

Sensitivity 94.5%

Specificity 95%

Type of analysis Nano particles based Fluoro-Immuno Assay(FIA)

Reading system Automated

Sample type Blood

REPRODUCIBILITY

Reading system Automated

Reproducibility near clinical threshold

95%

TEST PROCEDURE

Number of timed steps

One step

Time to result 15 minutes

SAMPLINGVolume of sample required

550µL

Throughput 90 tests

ADDITIONAL CHARACTERISTICS

Heat stability 15°C- 30°C

Storage conditions 20°C

End user profile Can be guided by the manual

Bio-safety requirement

Low

Shelf-life of reagents/device

Disposable strip

Training needs No training required

CONCLUSIONS

The product is superior compared to the existing technologies for the detection of pre- eclempsia: Three independent biomarkers increase

reliability of result Automated

A Point of Care approach

Huge market demand

SCIENTIFIC EVIDENCE

Nanoparticle based protein estimation:

Jiang et al (2009) He et al (2010)

REFERENCES:

Jiang, X., Weise, S., Hafner, M., Röcker, C., Zhang, F., Parak, W.J. and Nienhaus, G. U. (2009) Quantitative analysis of the protein corona on FePt nanoparticles formed by transferrin binding J R Soc Interface 7, S5-S13

He, Y., Li, Y. and Hun, X. (2010) Polymer nanoparticles as fluorescent labels in a fluoroimmunoassay for human chorionic gonadotropin Microchimica Acta 171:393–398

THANK YOU!

SCREENING TESTS AND THEIR LIMITATIONS Current Diagnosis

Measuring blood pressure (>140/90) protein concentration in urine (>300mg/dL)

Blood tests: liver, kidneys, platelets number.

Uterine artery Doppler ultrasound

Non stress test or biophysical profile: Check if baby is getting sufficient O2 and nutrients Response of baby’s heart rate relative to baby’s movement

Limitations : Time Consuming

Tendency of false positive result is high

MOST RECENT – ALERE This technique uses immuno fluorescence.

It is based on the PlGF marker

Launched in Europe in January 2011.

PRODUCT SPECIFICATION