JC Virus and PML Overview:
The John Cunningham virus more commonly known as the JC Virus is a common virus to which the Journal of Neurosciences has stated between 70% and 90% of people around the world have in their bodies. Most people carrying the JC virus will never know it and are unlikely to suffer any effects of the virus. It is commonly found in urban sewage worldwide, leading some researchers to suspect contaminated water as a typical route of infection. A study completed in 2006 displayed that by the age of 10 years some 40% to 60% of the global population is JCV positive.
A small percentile of individuals afflicted with multiple sclerosis (MS) however can be at risk from the JC virus when as the virus can be activated when an individual’s immune system is compromised by some immune system suppression medications known as multiple sclerosis disease-modifying therapies. The virus can be carried into the brain where it infects white matter of the brain and attacks brain tissue. The infection is called progressive multifocal leukoencephalopathy or PML for short. PML can be very disabling and even fatal.
Details:
Progressive multifocal leukoencephalopathy (PML) is a disease of the white matter of the brain, caused by a virus infection that targets cells that make myelin–the material that insulates nerve cells (neurons). Polyomavirus JC (often called JC virus) is carried by a majority of people and is harmless except among those with lowered immune defenses. The disease is rare and occurs in patients undergoing chronic corticosteroid or immunosuppressive therapy for organ transplant, or individuals with cancer (such as Hodgkin’s disease or lymphoma). Individuals with autoimmune conditions such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosis — some of whom are treated with biological therapies that allow JC virus reactivation — are at risk for PML as well.
The symptoms of PML are diverse, since they are related to the location and amount of damage in the brain, and may evolve over the course of several weeks to months. The progression of deficits leads to life-threatening disability and (frequently) death. A diagnosis of PML can be made following brain biopsy or by combining observations of a progressive course of the disease, consistent white matter lesions visible on a magnetic resonance imaging (MRI) scan, and the detection of the JC virus in spinal fluid.
The JC virus often attacks when an individual’s immune system is weak. People enduring multiple sclerosis already are at risk because of the autoimmune disease that is compromised by the disease. Most cases of PML infection have been related to specific disease-modifying therapies though there have been a few instances of PML occurring with people not engaged in disease modifying treatments. Specifically, natalizumab (Tysabri), dimethyl fumarate (Tecfidera), fingolimod (Gilenya) as well as corticosteroids have had instances of PML occur. Previous treatments with medications including cyclophosphamide, methotrexate, azathioprine, mitoxantrone or mycophenolate mofetil, appear to also increase risks that a person who has MS will develop PML after exposure to the JC virus.
In 2012, the US Federal Drug Administration (FDA) approved the Stratify JCV Antibody ELISA test in an effort to better detect if the virus exists within a persons body. A second generation test enhancing the original tests accuracy was released a year after. A positive test result does not indicate that a person with multiple sclerosis will develop a PML infection however only people who have the JC virus can develop PML. Additionally even if an individual tests negative for the JC virus that does not mean that the person cannot contract it at any time during treatment. According to the FDA the longer a person takes immune suppressing medications the higher the risk will be for that person to become infected.
PML is not normally a very strong infection however the problem with PML is getting effective medications to the brain.
As a result, it is advised as part of your multiple sclerosis treatments to be regularly tested to see if you have been infected especially when engaged in a disease-modifying treatment that has had occurrences of PML infection. Your neurologist can inform you how often you should be tested for the JC virus.
JC Virus and PML Treatment:
Presently there is no cure for the JC Virus.
Towards defeating a PML infection the best available therapy is a reversal of the immune-deficient state since there are no effective drugs that block virus infection without toxicity. The reversal may be achieved by using plasma exchange to accelerate the removal of the therapeutic agents that put patients at risk for PML. Several new drugs that laboratory tests found effective against infection are being used in PML patients with special permission of the U.S. Food and Drug Administration. Hexadecyloxypropyl-Cidofovir (CMX001) is currently being studied as a treatment option for JVC because of its ability to suppress JVC by inhibiting viral DNA replication.
Additionally, there are several research studies currently taking place in an attempt to rapidly defeat PML infection.
What is the Prognosis of PML Infection?
In general, PML has a mortality rate of 30-50 percent in the first few months following diagnosis but depends on the severity of the underlying disease and treatment received. Those who survive PML can be left with severe neurological disabilities.
Discussing PML with your Neurologist:
It is important to discuss your risks in respect to developing the PML infection and how medications you may be taking affect the risk factor of PML. Your neurologist may wish to conduct a test as a cautionary measure especially in the cases of prescribing or consideration of the disease modifying therapies, Tysabri, Tecfidera or Gilenya all of which have had cases of PML occur.
These testing will detect whether a individual has the JC virus and also measures the level of the virus present in the person’s body. This can help determine the risk assessment when considering beginning a disease modifying treatment therapy as well as on-going risk if a patient is already engaged in a therapy known to have had incidents of PML infection.
While the incidents of PML in multiple sclerosis afflicted individuals remains low in comparison to the 2.4 million people globally estimated to have the disease it is important to understand the risks and periodic testing done by your health care team in respect to the JC Virus and PML.
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