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Method for measuring lipoprotein lipase activity in human plasma for drug development and hypertriglyceridemia research

Country of Origin: Estonia
Reference Number: TOEE20180412001
Publication Date: 16 April 2018

Summary

An Estonian research group has developed a novel calorimetric method for quantitative measurements of lipoprotein lipase activity and interactions in human plasma. 

The research group is looking for partnerships with drug development companies, research groups that explore metabolism of plasma triglycerides, and hospitals researching hypertriglyceridemia in patients. Preferred forms of collaboration are licencing, service and research agreements.

Description

Recent studies suggest that hypertriglyceridemia (elevated levels of plasma triglycerides) is an independent risk factor for atherosclerosis. Hypertriglyceridemia has been identified as an early event in the development of type 2 diabetes. It is also common in the case of metabolic syndrome, obesity and renal diseases. 

It has been estimated that about 30% of Western population suffers from hypertriglyceridemia. One possible reason for hypertriglyceridemia is reduced hydrolytic degradation of plasma triglycerides by lipoprotein lipase, a key enzyme in the metabolism of triglyceride-rich lipoproteins.

Due to the complex regulation mechanism, it has been difficult to mimic in vitro the physiological conditions under which lipoprotein lipase acts. Up until now, most studies on lipoprotein lipase have been done using artificial substrate systems of radiolabeled, fluorogenic or chromogenic substrates, or isolated triglyceride-rich lipoproteins. However, these measurements are not sufficient to understand how lipoprotein lipase acts in vivo and how activators and inhibitors influence its activity in this situation.

Thus, there is an urgent demand for novel methods that allow to examine lipoprotein lipase activity and interactions in human plasma in real time. The Estonian research group is developing a calorimetric method that overcomes a number of limitations of other techniques for measurement of lipoprotein lipase activity.

The method provides a continuous assay using the observable heat rate that is directly proportional to the rate of the lipolysis. Measurements can be performed in non-diluted human plasma. Raw data obtained by this method are presented as thermograms in which the changes in the heat rate (heat flow, thermal power, heat flux) are monitored at a constant temperature. The method is easily automated. Effect of regulators and drug candidates on lipoprotein lipase activity can be tested in a human plasma environment.

In the clinical lab, the method can be used to find out whether hypertriglyceridemia in patients is caused by reduced amounts of active, heparin-releasable lipoprotein lipase or by an unfavorable composition of the patient’s plasma. Thus, using this method, it is possible to characterize plasma samples according to their properties as lipoprotein lipase substrate. This is a new way to analyse dysfunction in plasma lipoprotein metabolism that is not attainable by other technique.

The research group is looking for the following types of collaboration:
1) Out-licensing or service agreements with drug companies developing drug candidates for treatment of hypertriglyceridemia.

2) Collaborative research with research groups that explore metabolism of plasma triglycerides.

3) Service agreement or collaborative research with hospitals investigating the reasons of hypertriglyceridemia in patients.

The research group is also open to other types of collaboration.

Advantages and Innovations

The uniqueness of the method is that it enables measurements in non-diluted human plasma in real time. This means the results obtained are more complex and give more information, making testing of drug candidates and regulators more efficient. Currently, there are no know alternative technologies enabling that.

Stage Of Development

Under development/lab tested

Stage Of Development Comment

The method is available for demonstration

Requested partner

The research group is looking for different types of collaboration:

- either service or licensing agreements with drug development companies working with candidates to treat hypertriglyceridemia. The research group can offer drug screening services, and is interested in out-licensing their technology in the long run.

- collaborative research with universities and research institutions working with metabolism of plasma triglycerides. The research group is also open to developing and submitting joint project applications.

- joint research or service agreements with hospitals investigating the reasons of hypertriglyceridemia in their patients.

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