Arpita Sarkar
Research Scholar, Indian Institute of Chemical Technology (CSIR), Hyderabad 500007, A.P
E-mail: arpita1226@gmail.com.
What would you do if you feel sick today? You would certainly head to a doctor's clinic,get yourself tested and probably swallow a pill or take an injection shot in your arm. Chances are, you may get cured. But what if you are found to have a less common, complicated genetic disorder? Surely these traditional medicines wouldn't be enough.
Scientists think bigger. That's why we are in the era of 'gene therapy.
Scientifically speaking, we all are living, breathing, moving, talking complex biomachines. But looking back, each one of us started life as a simple single cell that multiplied and remultiplied to trillions of others. These could be called the body building material or 'basic units'.All of them have special duties:so we have heart muscle cells pumping blood, nerve cells passing electrical messages, skin cells making body pigment and so on. Yet on the inside,each cell is basically the same. Each one harbours the same genetic information, written in a linear code of 4 letters or bases A,T,G,C,on a long coiled thread of DNA.So how is this possible?
The answer lies in genes-the essential DNA switches that can turn on or off and specify which cell should do what it needs to do.
Way back in 1970s and 80s,researchers working on approaches to treat genetic disorders, asked if it was possible to repair or replace the faulty genes with functional,'good' ones. This is like fixing a problem at its rootsand thus begangene therapy(GT) for therapeutics. Thetopic was first discussed by scientists Theodore Friedmann and Richard Robin in an article in Science, 1972.
Then in the 1990s, Ashanti de Silva,a 4 year old girl, in the United States, became the first patient to receive this magic therapy. Receiving a shot of repaired white blood cells, she was cured of ADA(Adenosine deaminase)deficiency, a rare immune disorder,that would have killed her otherwise. Ever since, GT has had its highs and lows, with fabulous results in lab tests and not so frequent triumphs in clinical trials. Between 2006 and 2013, there have been moderate successes with treatment of patients with Parkinson's disease, multiple myeloma, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), X linked severe combined immunodeficiency(SCID) and Leber's congenital amaurosis.
If scientists are treating you with GT, they would choose any of the 4 methods.
- Insert a functional gene anywhere in your DNA.
- Exchange your bad gene with a good one
- Repair your defective gene
- Modify the cellular regulation of the abnormal gene.
Commonly they would use a virus to carry the custom-made gene into the body. They might also fire a DNA(coated with lipids or naked) directly to the inside.
Today, the two GT obstacles nagging researchers are: the introduced gene expresses for a very short time and the immune system refuses to incorporate it. Added to these are: questionable safety of using viral vectors,risk of tumorigenesis and inability to combat multigene disorders like heart disease, high blood pressure, Alzheimer's disease, arthritis and diabetes.
What was touted as a medical breakthrough at its conception, has now gradually given in to these potential health risks and technical barriers. This has been enough to scare away several biotechnological and pharmacy industries in the last decade. But there is hope in hand,still. On July, 2013, researchers in Texas have announced curing the deadly WASP(Wiskott-Aldrich) syndrome, by letting a weakened lentivirus carry a normal gene into the cell. Glybera,a GT remedy for lipoprotein lipase deficiency(LPD), has already been approved for clinical use by the European Medicines Agency in 2012 and is expected to hit the markets by late 2013.
Progress is slow but steady. Eventually, in a few years from now, we would have this miraculous therapy ready in our hands.