PROGRESSION IN MOLECULAR MEDICINE

On August 7, 2015, a delegation of the PLN Foundation visited the Mount Sinai hospital in New York City to talk to Dr. R.J. Hajjar (see picture). Their 4-year scientific research work has recently been published: they developed iPS-cells (“induced Pluripotent Stem” cells derived from skin or blood cells) made from skin tissue and transferred these cells in CardioMyocytes (CM or cardiac muscle cells).


Why is Dr. R.J. Hajjar interested in the Arg14-del (PLN) disorder while it very rarely occurs in the USA?

This interest mainly comes from his interest for Serca2: that is the calcium pump causing all types of heart failure. Because this disorder directly intervenes with it, this is a good start to also begin to learn about other types of heart failure.

Dr. R.J. Hajjar


Their study approach

They approached this study in 2 different ways:

  1. They cut the piece of wrong DNA (both strands) in the iPS-cells with molecular scissors and replaced it with a correct one (both with an AAV viral vector* technology). They next made CM (CardioMyocytes) from these iPS-cells which were correctly working. The entire study was conducted using dishes with cells (not on living animals or humans).
  2. They also developed CM from the iPS-cells containing the disorder and inserted a piece of miRNA** with an AAV viral vector* technology which made the correct PLN again. Because the DNA consists of 2 strands, the one strand all corrected it in the right ones.

Results?

What happened is extremely exceptional, according to Dr. R.J. Hajjar. If you create more good PLN because of the inserted miRNA**, the effect of the wrong part disappears without having to suppress it. Thanks to this overexpression process, the effect of the wrong part is adjusted again on cell-level.

This way, they have found 2 ways in which it can be resolved. The cutting and inserting process is very complex (but scientifically very interesting) because you can also just cut and/or insert it in a wrong place.

* AAV viral vector technology = Adeno-Associated Virus
** miRNA = non-coding-RNA (RNA molecule that is not translated into a protein)

 

Now and in the future…

Dr. R.J. Hajjar and his research team are now experimenting on mice in 3 different ways:

1. The AAV viral vector technology with miRNA for PLN to cause overexpression.
2. Deactivate the effect of the wrong PLN and insert the correct one with AAV viral vector technology.
3. Cut the wrong out and insert the correct one with AAV viral vector technology (scientifically very interesting but very complex and still quite far away from application).

This time next year (2016), he expects to have finished all research data gained from the mice which will provide more insight in the possibilities.

The next step they are working on right now, is testing the procedure on a larger type of animal. The estimated costs are between $200,000 and $300,000. The first and the second option could already lead to application fairly quick (5-10 years). To be continued.

WANT TO KNOW MORE about ongoing PLN-related research projects? Stay informed through the website of the PLN Foundation.

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