·
Links
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Questions for Dr.
Krassowska
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Electrical
Therapies Web Page (A page describing Dr. Krassowska’s research group and
the work that they did.)
(919)-660-5105
(919)-660-5405
Electroporation is an experimental process that creates pores in cell membranes with electrical impulses, allowing drugs or DNA to be introduced. Dr. Wanda Krassowska, Associate Professor of Biomedical Engineering at Duke University, has focused on mathematical modeling of the problem of electroporation.
There are many advantages to electroporation. One significant advantage is that unlike gene therapy, which uses viruses to insert DNA into cells, electroporation is clean, with no biological residue. Using electroporation to introduce drugs represents an effective combination of electricity and drug treatment. Future potential applications of electroporation include the introduction of very large molecules to cells.
There are many practical applications of the electroporation techniques that Genetronics is developing. In oncology, in vitro studies have been done on larynx, melanoma, pancreatic, liver, and prostate cancers. Clinical trials have been done with head and neck cancer, pancreatic cancer, liver cancer, metastatic melanoma. A 90% regression rate was found after one treatment of electroporation for metastatic melanoma. In gene therapy, clinical trials have been done with ex vivo hemophilia treatment. Electroporation has also been applied to cardiology – experiments have been done on the delivery of drugs to prevent restenosis. Also, transdermal drug delivery, the topical delivery of drugs, has been researched.
Problems still exist with electroporation, though. There is the danger of killing cells with
too big a pulse or too many pulses of electricity. Also, if pulses are near muscle tissue, they can cause
contraction of muscles. So mathematical
modeling involving parameters (such as strength, duration, shape, number, and
rate) of the electrical pulse is used to better control electroporation. Krassowska has developed an asymptotic model
of electroportation that is applicable to spatially extended systems (such as
the cell) and can predict the size of the resulting pores, the pore density,
and the uptake of drugs. This model is
more simplistic than the previously used Smoluchowski’s equation and is easier
and less costly to solve. The model
enables researchers to improve understanding of electroporation.
Wanda Krassowska, Ph.D. was born on November 1, 1954 in Warsaw, Poland. She received a M.S. in Mechanical Engineering in 1978 at Warsaw Technical University. She also acquired the position of Research Associate at the Institute of Biocybernetics and Biomedical Engineering in Warsaw until 1981 when she then became the head of the Computer Laboratory for Biomedical Systems Research until 1983. Dr. Krassowska came to America as a visiting Fulbright Scholar at the Basic Arrhythmia Laboratory at the Duke University Medical Center and earned her Ph.D. in Biomedical Engineering here at Duke in 1987. She became the Research Assistant Professor in the Biomedical Engineering Department, Assistant Professor, and now the Associate Professor of the department. Her research interests include drug delivery and electroporation, which she researched on sabbatical at Genetronics, Inc. in San Diego, and electrophysiology, with emphasis on the study of cardiac dynamics under strong electric fields.
When you break apart the cell
membranes, do the pores always close up?
When you do the shock, does it hurt
the patient?
How do you introduce the drug into
the patient?
What kinds of cancer are
susceptible to this treatment?
What is the role of mathematical
modeling in this research?
What is the purpose of injecting
DNA into a cell?
Are there any successful cases of electroporation used in gene therapy?
Is
there another way to get through the cell membranes?
Is there a
reason why electroporation works better to treat diseases than gene therapy?
Electroporation is the formation of water filled “holes” in
the lipid bilayer matrix of the membrane.
No, sometimes the cell dies.
No, it does not hurt them too much, because it is done under
local anesthesia, but sometimes if the shock is too close to the muscle, the
patient has muscle contractions.
You inject the drug directly on the spot
being treated and apply an electrical impulse.
Any kind of cancer that is localized would be susceptible to
this king of treatment, including internal cancer.
The success of electroporation based treatment depends on
the parameters of the pulse. A
mathematical model can help establish a link between pulse parameters and the
electroporation process.
Gene therapy. For
example, someone’s body is not making a certain type of protein, so you take a
fragment of DNA that tells the cell to make that protein, and insert it into
the cell so that the cell will be able to start making that protein.
Yes, hemophiliacs.
Membranes
have channel proteins embedded in them, but drugs are too big to fit through,
and the channels are very selective “like a bouncer in a night club.” Other
ways to get through the membrane are viral delivery, a DNA gun (where it
goes through the membrane like a bullet), or ultrasound.
There are certain diseases that electroporation works really
well to heal, and some that don’t.
Drugs are easier to get into the cell than DNA is.
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Created by Emily Carl, Casey McCain, and Mae Joyce Gay