State of the Art: GENE THERAPY- Pt 1

What is Gene Therapy?

Gene therapy is the term used for a biological treatment that is designed to introduce new active genetic material to living cells in order to increase or reduce a genetic product or products. These products can include either RNA or proteins or both. For the crudest of analogies, imagine the cell is a factory. This factory has assembly lines that currently build blenders. The blenders are great, but you also want to make toasters now. You send instructions to the factory to reconfigure some of its assembly lines to make toasters for at least part of the time. That is basically what is happening in gene therapy.

The most easily related example that I can think of where this technology could be useful is in Type I diabetes mellitus, where there is a deficiency in production of the protein, insulin, which is encoded by DNA on chromosome 11 in humans. An easy illustration of how a gene therapy could work would be to say that the gene for insulin production could be introduced to cells of a Type 1 diabetes patient so that their body would then be capable of generating insulin on their own. They would no longer need to take insulin shots to control high levels of blood sugar. I will stop there and now posit the emphatic caveat that the case of Type 1 diabetes is much more complex than I just described. The lack of insulin production is not because a gene is missing, rather it is because the cells that normally produce insulin are missing. In fact, diabetes might be better treated with a stem cell therapy than a gene therapy; but I digress (a topic for another State of the Art series). The main point of this ambling monologue is that, by using gene therapy, a new gene or genes can be introduced so that a cell can generate a product that it wasn’t previously generating in order to achieve a variety of net effects.

In the United States, there are currently as many as 30 clinical trials active or enrolling to test the safety and efficacy of myriad gene therapy, or gene transfer, strategies. The trials hope to find treatments for conditions ranging from X-linked Chronic Granulomatous Disease (CGD) where patients’ neutrophils cannot make a key protein necessary for infection defense to Advanced Pancreatic Cancer where a researchers are trying to test safety and dose response of delivering a “tumor killing” gene.

While there are dozens of gene therapy clinical trials and hundreds of labs worldwide conducting research with gene therapy technologies, there is still no FDA approved gene therapy product on the market; nearly 17 years after the first human gene therapy trial was conducted on a 4 year old girl with severe combined immunodeficiency (SCID) at the U.S. National Institutes of Health in 1990.

Why are gene transfers so challenging to develop and administer? There are many pitfalls. First of all, it is simply difficult to incorporate new genes into living cells, especially in a multicellular tissue system. Secondly, once the gene is there, it doesn’t always produce an active protein (or RNA). Thirdly, if the gene does work, it is very difficult, if not impossible, to turn it off, thereby rendering overdoses and immune reactions virtually impossible to treat. Forthly, it is difficult to target genes to show up in the correct cells while not also affecting cells that don’t need the gene. Lastly, there are some questions about potential to pass on the therapeutic gene to offspring who won’t need it.

These issues are currently being addressed with variable success in research around the world. They are testing many different genes and gene deliver strategies in hopes of harnessing biology’s machinery to treat diseases. In the next installments of State of the Art: GENE THERAPY, we will talk about specifics of where the technology is right now. For now, chew on this one. Think of questions. Tell me I am an idiot. Thanks for reading. :)

Upcoming Posts!

State of the Art: GENE THERAPY- Pt2
Viral Delivery

State of the Art: GENE THERAPY- Pt3
Non-Viral Delivery

AVIAN FLU- Will it ever take off?

A while back, there was a huge media scare about the avian flu. Media fear mongering alternately amuses and irritates me. The media often fills news gaps with whatever they can come up with that might terrify the populace and incite us to improve their ratings and sales. Perhaps one day we can write an article about the psychology behind scare tactics in media programming. Today, however, I am going to talk about the avian flu and the flu in general.

How much do each of us really know about the flu? Before I started my formal medical education, I could barely tell the difference between having the flu and having a bad cold myself. They are both viruses. Both result in the symptoms which can include sore throats, coughing, achiness, and headaches.

So what are the differences? Well, first of all, cold’s are caused by rhinoviruses. As the name implies, rhinoviruses cause symptoms in the nose. That snotty, nasal congestive hell that we all go through at least once yearly can be blamed on the common cold. Generally speaking, the common cold stays in the upper respiratory tract. The flu, or influenza as it is more formally known, is caused by the orthomyxoviridae family of viruses. While some of its symptoms are shared with the common cold, it is noted for knocking us completely out of commission for a day or two. All we can do is just lay in bed and whine to our significant others. In the worst cases, the flu can cause pneumonia. For those of you who have never experienced this fun condition, it’s a lot like drowning in your own mucous. It can be fatal, especially in very young or very old patients. Not fun.

So now that we know what your everyday garden variety flu can do, what was the deal with the avian flu that was terrorizing the world right up until the media forgot to talk about it? Well, there are a few different kinds of influenzas. Humans are most affected by Influenzavirus A, Influenzavirus B, and Influenzavirus C. Within those families, we are most affected by Influenzavirus A. Now make sure you are sitting down for this next part…All viruses in the Influenzavirus A family are kinds of avian flu viruses that have adapted to infect humans! So what I am saying is that you’ve probably been infected by and survived the avian flu! Congratulations!

That’s right, most flu viruses that infect humans are originally avian viruses. Then why the big deal about this new avian flu? Well, it seems that this particular strain, the H5N1 strain, of avian flu is quite deadly when contracted by humans. Fortunately for our species thus far, though we can contract the virus directly from birds, we cannot pass the virus on to other humans.

As CNN, FoxNews, and Katie Couric have all informed us many times, many leading epidemiologists believe that it will only be a matter of time before the H5N1 strain mutates into a form by which humans can infect each other directly. Mass hysteria will follow. Everyone will dress up in football pads and have Mohawks like they did in the post apocalyptic world of Mad Max. It’ll be great. Really.

Just kidding. We won’t be wearing football pads.

The reality is that we don’t know when or if this strain of bird flu will ever undergo the mutation of its protein shell necessary to cause a human pandemic. While our governments should take precautions in case something does occur, there isn’t a whole lot any of us can do as individuals about it right now unless we want to volunteer for vaccine clinical trials (this would probably involve being injected with a watered down form of the avian flu) or become research scientists devoting our lives to studying influenza viruses. Yeah, I don't want to either. Basically, don’t stress about this. Enjoy your daily lives until you hear Katie Couric tell you that the virus has finally mutated. She’ll be right on it. I promise.

Then stay as far away from public transportation and airports as you can possibly get.