Motor Neurone Disease (MND) Linked to HIV-Like Retroviral Cause

Lennon, M

Introduction

Motor Neuron Disease (MND) is an idiopathic, fatal, neurodegenerative disease of the human motor system. This study explores the involvement of a novel protein, B cell lymphoma/leukaemia 11b (Bcl11b) in MND and potential retroviral links that this has. Bcl11b is a multifunctional zinc fiiger protein transcription factor. It functions as both a transactivator and genetic suppressor, acting both directly, binding to promoter regions, and indirectly, binding to promoter bound transcription factors. It has essential roles in the differentiation and growth of various cells in the central nervous system (CNS), immune system, integumentary system and cardiovascular system, to the extent that Bcl11b knockout mice are incompatible with extra-uterine life. It is involved in keeping HIV and possibly other retroviruses in a latent state. Consequently, the following hypotheses were tested: BCl11b is elevated in MND because of immune involvement (inflammation), compensatory upregulation in response to neuronal death, or an underlying, possibly causative retrovirus.

Methods

40 healthy, 17 inflammatory and 34 MND CSF samples were collected and analysed. Bcl11b levels were assessed using immunoblot analysis, neurofilament light chains were measured using ELISA, CSF protein by BCA assay and CSF DNA by nanodrop spectrophotometry. Results were then analysed using JMP10. Reverse transcriptase was measured by PCR.

Results

Bcl11b was found to be significantly elevated (p<0.0001) compared to healthy and inflammatory controls, in particular it was found to be elevated in a subset of patients. There was no association with measured markers of inflammation or cellularity but there was some associatoon with neurofilament light chain (p=0.03) and ALS functional rating score (p=0.022). Reverse transcriptase was positive in 1 of 34 MND samples and associations with Bcl11b became difficult to analyse.

Discussion

It seems unlikely that Bcl11b is elevated in MND due to inflammation or infiltrating cells. It is evident that its elevation is related to apoptosis of neurons in MND and it also has a strong correlation to functional decline of the patient. Given recent research from Li et al finding a causative link between Bcl11b and human endogenous retrovirus K this research corroborates the hypothesis that MND can be caused by HERV-K and cells actively try to suppress it.