Target Health Blog

Progressive Multifocal Leukoencephalopathy (PML)

April 29, 2019

Infectious Disease

Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal viral disease characterized by progressive damage or inflammation of the white matter of the brain at multiple locations. In general, PML has a mortality rate of 30-50% in the first few months, and those who survive can be left with varying degrees of neurological disabilities. PML occurs almost exclusively in patients with severe immune deficiency, most commonly among patients with acquired immune deficiency syndrome (AIDS), but people on chronic immunosuppressive medications including chemotherapy are also at increased risk of PML, such as patients with transplants, Hodgkin's lymphoma, multiple sclerosis, psoriasis, and other autoimmune diseases.

PML is caused by the JC virus, a common and usually innocuous virus that normally resides in the kidneys of anywhere from one- to two-thirds of the population. Rarely, in patients who have had their immune system suppressed due to conditions such as HIV/AIDS or because of immunosuppressive medications such as many cancer therapies or some treatments for autoimmune diseases, JCV can change to a form that infects cells in the brain. Symptoms of PML include clumsiness, progressive weakness, and changes in vision, speech, and sometimes personality

According to an article published in the New England Journal of Medicine (10 April 2019), the anti-cancer drug pembrolizumab, whose mechanism of action blocks the interaction between two proteins, PD-1 and PD-L1, has shown promise in slowing or stopping the progression of PML. Normally, these proteins work by putting the brakes on the immune system to limit excessive inflammation. However, some tumors that have PD-L1 on their surface can exploit this “off switch,“ limiting the immune system's ability to attack the cancer. Recent studies of PML patients have suggested that this mechanism may also be involved in JCV brain infections.

For the study, 8 patients at the NIH Clinical Center, all of whom had signs of worsening PML, were treated with pembrolizumab. The status of their infection was monitored by MRI scans of their brains and by checking the levels of JCV in their cerebral spinal fluid (CSF). Results showed that in 5 of the 8 patients, the amount of circulating virus was reduced following treatment with pembrolizumab. Importantly, these patients' symptoms improved or stabilized, and their brain MRIs showed shrinking of infection-related brain lesions.

Currently, the authors are working on discovering markers for individuals at high risk for PML and for earlier detection of infection. The authors also indicated that larger clinical trials conducted under more controlled conditions are necessary for a better understanding of the effect of pembrolizumab or similar medicines on PML, and that work is currently underway to determine the best way to take those next steps.

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