The JC Virus
The reason for this post is two
fold: (1) to bring awareness and spread information about a little known
disease and (2) people close to me were recently affected by this disease. The
disease in question is Progressive Multifocal Leukoencephalopathy, or PML as it
will be abbreviated hereafter.
PML is a rare viral disease
characterized by damage to myelin in the brain. It is caused by the JC virus.
Now before we get into the specifics of PML or the JC virus itself let’s review
some basics of how a virus works. Check out this quick video produced by NPR on
how a virus infects another cell.
The video talks about how the flu
virus invades our bodies but the same principles apply for any virus. The crazy
thing is our bodies are full of all kinds of viruses all the time. That means
our immune system is constantly trying to stay one step ahead of the invaders.
The JC virus is actually present in
almost all of us (90%) as we have all probably been exposed at some point in
our lives. It is constantly trying to replicate itself but in a healthy
individual our immune system can suppress the virus and it is not a major
concern. People that have compromised immune systems (i.e. AIDS patients or
people exposed to chemotherapy) are at a greater risk of the JC virus causing
harmful side effects due to their immune system’s inability to fight the virus
anymore.
Essentially, once the virus isn’t
receiving resistance from the immune system it is free to travel throughout the
body and cross the blood brain barrier, which gives it direct access to the
central nervous system. The blood brain barrier is a thin layer of endothelial
cells that separates the circulating blood from fluid in your brain. It allows
essential nutrients such as glucose and other metabolic products entry into
your brain but keeps potential toxins out. Other organs do not have this added
level of security because it is pretty easy to replace cells in other areas of
your body. Neurons, however, exit the cell cycle early on and do not easily
replicate themselves so it is essential for your body to protect and sustain
the ones you do have.
The brain consists of white matter
and gray matter. Gray matter is cell bodies. White matter is axons (which
extend off the cell bodies and connect to other cells in the brain). The axons appear
white in the brain because of myelin, which is a lipid (fat) that insulates the
axon and allows the electrical signal to travel down the axon faster. The JC
virus attacks this white matter by killing the cells that are responsible for
producing it. These cells are called oligodendrocytes in the central nervous
system. In short, the virus takes away the brain’s ability to communicate
messages efficiently and, eventually, not at all. If there is not an electrical
signal triggering the release of chemicals from the ends of the axons, that
vital signal is not being transmitted to other nearby cells. Without cells
receiving normal input and nutrients, the cell itself will eventually die.
Unfortunately, viruses are
extremely hard to treat. As we saw in the video earlier, viruses “hijack” a
cell’s DNA (or RNA if it is an RNA virus) and use the cell’s own DNA synthesis
machinery to reproduce itself. Antiviral medications are really the only hope
of stopping something like the JC virus and PML. A new drug, Brincidofovir, is
currently in clinical trials for fighting PML. Brindcidofovir gained some
momentum and publicity for being effective against the Ebola virus when treating
patients here in the U.S. It is a modified form of another drug called
cidofovir. The drug is connected with a lipid (fat) that makes it very easy to
get into the cells. Cells have a membrane made up of lipids to keep bad stuff
out. By attaching a lipid group to this drug, Brincidofovir can enter the cell
very easily and increases its intracellular concentration, which makes it more
ideal for fighting viruses. In addition to that, Brincidofovir has great oral
bioavailability. This means that when administered orally, the drug is
relatively unchanged by the time it reaches the circulatory system (which will
transport it to the brain). Brincidofovir has shown good efficacy in fighting
viruses in the few clinical studies they have done with it and in mice with
suppressed immune systems that were injected with a virus.
Regardless of promising drugs in
development, the prognosis of PML is not good at all. 50% of patients die
within months of diagnosis and those that survive have serious neurological
issues. The brain really takes a hard, fast hit with this virus. Overall, I
hope this post will help spread awareness for a rare infectious disease of the
brain and help inform other families that have had to deal with this
devastating illness about the science behind it.