Baby Steps Towards New Cystic Fibrosis (CF) Treatments

Finding New Ways to Kill CF-Related Bacteria
December 2, 2011 One of the biggest problems for people with cystic fibrosis (or CF) is lung infections. Their lungs fill with a thick mucous that certain bacteria thrive in. Medicines and the patient's immune systems start off doing a pretty good job fighting off these bacteria. But over time they become harder and harder to fight.

Scientists are figuring
out ways to battle
CF-related bacteria
like these.
In a new study, researchers looked at how the DNA of these bacteria changed during an infection. They found that certain changes were shared by resistant bacteria that were found in many different patients. Since all of these different bacteria are resistant to treatment, at least some of the shared DNA changes are probably to blame. Finding these changes (and the genes they affect) is the first step to finding new treatments for bacterial infections in CF patients. The next step is to find the genes that really are important. The final step is for scientists to design medicines that can affect those genes and so maybe affect the bacteria. These kinds of studies won't lead to a cure for CF. But it might help CF patients live longer. And that is obviously a big deal. Back in 1955, children with CF were not expected to make it to grade school. Now they have a very good chance to live into their mid 30's. Maybe some of the new medicines that come from this study can extend this even further. And the approach used in this study is not just useful for CF. It can be used for other infections and for diseases like cancer too. All of this is possible because reading DNA keeps getting cheaper and cheaper. Studies that could not have been done 5 years ago are easily done now. This should lead to many more gene targets for many different diseases and hopefully, more treatments too.
Battling Bacteria
It is hard to figure out which changes in bacterial DNA lead to resistance. You have to sift through millions of A's, C's, G's, and T's and thousands of genes to find the single difference that matters. To make things even trickier, different bacteria of the same species can start out with very different DNA. They can be so different that it can be hard to compare bacteria from different patients. Without being able to do that, it is nearly impossible to figure out which of the many bacterial changes that happen over time are important and which aren't.

Finding the new DNA changes that
matter can be tricky.
This last point was not a problem in the current study. The researchers focused on 39 CF patients who were infected with the same bacterial strain in an outbreak in Boston. In other words, all 39 patients were infected with bacteria that had the same starting DNA. This made analyzing the DNA much simpler. Over the 16 years between when these patients were infected and the study started, doctors collected and froze 112 different samples. These were taken from different patients at various times over the patients' treatment. The researchers looked at every A, G, C, and T in all 112 samples and compared them to each other. After a lot of analysis, they found a certain set of changes common to all of the different bacteria. Two of the genes they identified were known to cause resistance in other cases. This gave the researchers some confidence that at least some of the other 15 genes might be important too. The next step will be for scientists to investigate these 15 genes in the lab and see which ones really matter to resistance. Once this is done, they can try to find chemicals that target that gene and hopefully make the bacteria sensitive to treatment again. There is still a long way to go and no new treatments may come out of this study. But it does show other scientists how to go about finding new gene targets. Finding medicines is much simpler if you know the gene you're targeting. This method will almost certainly bear fruit eventually. After all, similar approaches have worked before to discover new treatments for certain cancers.

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Controlling Cancer
In some ways, cancers are very similar to resistant bacteria. Both become a problem when certain DNA changes turn the wrong genes on or off. In bacteria, the cells become resistant to treatment. In cancers, the cells start growing uncontrollably or ignore requests that they die. (They can also become resistant to treatment like bacterial cells but that will have to wait for another discussion.)

Gleevec specifically
targets a type of
cancer called CML.
Most current cancer treatments focus on killing all growing cells. This often kills the cancer but it also causes patients to have many nasty side effects (like hair loss, nausea, anemia, etc.) because all growing cells are targeted. And these treatments don't always work. If scientists could find the genes that are affected in specific cancers, then they could make medicines that target that gene instead of targeting all growing cells. This should decrease the number of side effects. This approach isn't just science fiction either. Scientists have actually pulled it off with a number of different medicines. The first success story was one called Gleevec. A certain blood cancer called CML is often caused by a DNA change called the Philadelphia chromosome. What happens in this case is two genes called bcr and abl get stuck together. This new hybrid gene causes the cells to grow uncontrollably. When scientists figured this out, they started to look for chemicals that might affect what this new gene was doing. Eventually they got to Gleevec. Gleevec keeps this new gene from telling the cell to keep growing. This causes the cancer to stop growing. Gleevec is now one of the most effective treatments available for CML. Until the CML becomes resistant that is. Cancer is a very slippery beast - new DNA changes crop up in the CML cells that make them resistant to Gleevec. So scientists are uncovering those new DNA changes and are coming up with new treatments based on what they find. And these will work until the cancers develop new DNA changes again. These kinds of battles against cancer and resistant bacteria will rage on for the foreseeable future. Thank goodness newer technologies are giving us the weapons we need to keep these invaders at bay.