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

A G7 DIAGNOSTICS PRESENTATION

Helena Gwani Ayotunde Awosusi Daniel Igwe Priyesh Waghmare Srishti Jain Vinie Varkey T

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,

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

10% of all
pregnancies

12% of maternal
deaths

1/3rd of pre mature

births

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/annotatedwebliography-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 DIAGNOSIS
Method Description Limitations

Blood pressure Protein concentration in urine

(>140/90) (>300mg/dL)

Time consuming
Complex Low reliability

Blood tests: liver, kidneys, platelets number.

Late diagnosis Rate of false positive result is high.

Uterine artery Doppler ultrasound

HOW CAN WE APPROACH THE PROBLEM?

The ideal Screening test: Simple

Noninvasive Rapid

Inexpensive
Early detection

Highly sensitivity & predictive

MARKET NEED

12% of maternal deaths

Global prevalence of pre-eclampsia

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.

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. 1.

Biochemical Marker sflt-1 (Soluble fms- like tyrosine kinase)

Plasma Concentration Trimester 1 Trimester 2

Manifest Preeclampsia Early increase

--

high

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 with the dried reagents

Blood Filter Cells are separated from plasma

Three Internal Controls

Independent Positive High and low control zones and a nonspecific binding control

Timegate Hyrdrophobic surface ensures reaction time

Waste Reservoir
Excess sample collected in the periphery

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) 94.5%

Sensitivity

Specificity
Type of analysis

95%

Nano particles based FluoroImmuno Assay (FIA) Automated Blood

Reading system Sample type

REPRODUCIBILITY
Reading system Reproducibility near clinical threshold Automated 95%

TEST PROCEDURE
Number of timed steps
Time to result

One step
15 minutes

SAMPLING
Volume of sample required Throughput 550L 90 tests

ADDITIONAL CHARACTERISTICS
Heat stability Storage conditions End user profile Bio-safety requirement Shelf-life of reagents/device 15C- 30C 20C Can be guided by the manual Low 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., Rcker, 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 171:393398

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 babys heart rate relative to babys 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