3:20 PM
Dec 14, 2017
 |  BC Innovations  |  Product R&D

Opening doors in PML

How NIH and Neurimmune are collaborating and competing in PML

An NIH-led team has demonstrated that neutralizing antibodies can prevent infection of cells by mutant strains of JCV -- the virus responsible for the lethal brain infection PML. In a field with no clinical options, the results provide a rationale for a therapeutic alternative to NIH’s own early stage preventive vaccine.

Moreover, the paper, published in an October issue of Cell Reports, uncovered the mechanism by which the virus enters brain cells, a mystery that has counfounded the field.

Effectively, the study pits NIH as both collaborator and competitor of Neurimmune Holding AG, who provided the broadly neutralizing antibodies (bnAbs) and participated in the paper.

The same NIH team that led the study, headed by Christopher Buck, a senior investigator in the institute’s Laboratory of Cellular Oncology, has a prophylactic vaccine in preclinical development that aims to boost the immune response against John Cunningham virus (JCV) in patients on autoimmune therapy who are at risk for developing progressive multifocal leukoencephalopathy (PML).

PML has emerged as a serious liability for certain immunosuppressive biologics, most famously Biogen Inc.’s Tysabri natalizumab, marketed for multiple sclerosis. At least 14 other immunosuppressive drugs cause a similarly small but real risk of PML, although there is no unifying theme among them identified yet. Biogen also participated in the Cell Reports study.

The JCV virus is found in 60-70% of the population, and is benign in healthy individuals. But in patients with immunodeficiencies like AIDS, or receiving immune suppressing biologics, JCV can enter the CNS, where it kills oligodendrocytes and damages astrocytes, leading to severe inflammation. Infection manifests with focal neurologic deficits and can be fatal.

The problem faced by patients susceptible to PML is that they have “blind spots” in their antibody repertoires.

That leaves many autoimmune disease and some cancer patients with a tough decision: contend with the risk of a life-threatening infection or forgo treatment with a therapy that could help them.

While the virus’ identity is known, the field has been held back by a lack of understanding of how JCV infects the brain. In the new study, Buck and colleagues discovered that the mutant, pathogenic form of the virus takes an alternative entry route to the brain from the wild-type, providing a new target for blocking entry therapeutically.

Buck told BioCentury there’s room...

Read the full 1910 word article

User Sign in

Trial Subscription

Get a 4-week free trial subscription to BioCentury Innovations

Article Purchase

$100 USD
More Info >