Medical history: January 2012 Archives
Friday the FDA announced that it's permitting the marketing of the first test for antibodies to the JC virus (Stratify JCV Antibody ELISA test; Quest Diagnostics), the cause of progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals and now an official risk factor for the disease in patients taking Tysabri (generic name, natalizumab; Biogen Idec). (Delayed clarification: JC virus is the cause of PML, and antibodies to the JC virus are now an official risk factor for the disease in patients taking Tysabri.) The presence of anti-JC virus antibodies is added to the previously identified risk factors for PML of 1) a longer duration of Tysabri treatment (>2 years) and 2) previous immunosuppresant therapy. The risk of PML in the presence of all 3 factors is 11 in 1000, or 1.1%. The FDA reports that there have been 201 reported cases of PML among approximately 96,582 patients who have been treated with Tysabri (for the indicated conditions of multiple sclerosis or Crohn's disease) as of January 4th; the overall PML rate is consequently 0.21%.
The "JC" in JC virus stands for John Cunningham, and like the previously anonymous Henrietta Lacks of the immortal HeLa cells, this John Cunningham remains largely unknown. The virus itself is ubiquitous and harmless in most people (40%-60% of the general population are seropositive), but it creates a potentially devastating and often fatal white matter disease in immunocompromised persons.
A cursory search leads to a Google-available (or really, partially available) book entitled Human Polyomavirus, which was edited by Kamil Khalili and Gerald Stoner and published in 2001. The first 3 chapters concern the search for the cause of PML, which was first described or recognized in 1958 (first published paper by Astrom et al..."a hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin's disease"). Chapter 2, written by Dr. Gabriele M. Zu Rhein, a codiscover of JC virus, reveals that John F. Cunningham was a patient at the VA Hospital in Wood, Wisconsin, in the summer of 1970. Cunningham had Hodgkin's disease and "rather rapidly progressing neurologic deficits." He was given a diagnosis of PML during life on the basis of a brain biopsy and thereafter "expressed the wish that his brain should aid research into this fatal disease." A "new human polyoma virus" was subsequently detected by Rhein and her colleagues in Cunningham's postmortem brain tissue, and the virus was named JC virus in honor of the patient.
A Wisconsin death record reveals that John F. Cunningham was 36 (born August 30, 1933) when he died on July 12, 1970, in Milwaukee. As a military veteran, his likely service would have been in the Korean or Vietnam War.
01/26/12 follow-up: The 1971 Lancet article by Padgett et al indicates that Cunningham was 38 in 1970 (although his death certificate indicates that he was about 6 weeks shy of his 37th birthday at the time of his death). Cunningham had been diagnosed with Hodgkin's disease for 8 years before he developed a "progressive left central facial palsy, left hypoglossal palsy, and palsy of the left upper extremity" in the Spring of 1970. (His cancer had been treated with nitrogren-mustard derivatives since 1968.) These neurologic deficits were attributed to PML, a diagnoses confirmed by brain biopsy (which showed "pathognomonic oligodendrocytes along the periphery of demyelinating lesions") during life. He reportedly granted permission for the postmortem examination of his brain only (examination occurred 10½ hours after death). Gross and microscopic study confirmed the diagnosis of PML, and extracts of his brain were used to grow and identify the newly recognized intracellular virions in culture—which were dubbed JC virus.
The "JC" in JC virus stands for John Cunningham, and like the previously anonymous Henrietta Lacks of the immortal HeLa cells, this John Cunningham remains largely unknown. The virus itself is ubiquitous and harmless in most people (40%-60% of the general population are seropositive), but it creates a potentially devastating and often fatal white matter disease in immunocompromised persons.
A cursory search leads to a Google-available (or really, partially available) book entitled Human Polyomavirus, which was edited by Kamil Khalili and Gerald Stoner and published in 2001. The first 3 chapters concern the search for the cause of PML, which was first described or recognized in 1958 (first published paper by Astrom et al..."a hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin's disease"). Chapter 2, written by Dr. Gabriele M. Zu Rhein, a codiscover of JC virus, reveals that John F. Cunningham was a patient at the VA Hospital in Wood, Wisconsin, in the summer of 1970. Cunningham had Hodgkin's disease and "rather rapidly progressing neurologic deficits." He was given a diagnosis of PML during life on the basis of a brain biopsy and thereafter "expressed the wish that his brain should aid research into this fatal disease." A "new human polyoma virus" was subsequently detected by Rhein and her colleagues in Cunningham's postmortem brain tissue, and the virus was named JC virus in honor of the patient.
A Wisconsin death record reveals that John F. Cunningham was 36 (born August 30, 1933) when he died on July 12, 1970, in Milwaukee. As a military veteran, his likely service would have been in the Korean or Vietnam War.
01/26/12 follow-up: The 1971 Lancet article by Padgett et al indicates that Cunningham was 38 in 1970 (although his death certificate indicates that he was about 6 weeks shy of his 37th birthday at the time of his death). Cunningham had been diagnosed with Hodgkin's disease for 8 years before he developed a "progressive left central facial palsy, left hypoglossal palsy, and palsy of the left upper extremity" in the Spring of 1970. (His cancer had been treated with nitrogren-mustard derivatives since 1968.) These neurologic deficits were attributed to PML, a diagnoses confirmed by brain biopsy (which showed "pathognomonic oligodendrocytes along the periphery of demyelinating lesions") during life. He reportedly granted permission for the postmortem examination of his brain only (examination occurred 10½ hours after death). Gross and microscopic study confirmed the diagnosis of PML, and extracts of his brain were used to grow and identify the newly recognized intracellular virions in culture—which were dubbed JC virus.
