New research: 'Toxic effect' of cerebrospinal fluid in MND

diagram showing the effect of CSF on cells

August 2020: A review of scientific literature has revealed that cerebrospinal fluid obtained from people with ALS/MND is damaging to cells.

What is cerebrospinal fluid?

Cerebrospinal fluid (CSF) is a clear colourless liquid that surrounds most of the brain and spinal cord. The average human adult is believed to possess a total CSF volume of about 150mL, all of which is renewed three to four times in a single day.

CSF plays an important role in the human body, providing buoyant support to the brain and protecting it from mechanical damage. It is also involved in the regulation of various substances, including nutrients and waste products. In fact, scientists have recently discovered an important clearance system for the brain called the ‘glymphatic system’, with the CSF circulation being central to this clearance mechanism.

What is known about cerebrospinal fluid in MND?

Many studies have now shown that the constitution of CSF in people with the ALS form of MND differs from that in healthy individuals. For instance, it contains higher levels of TDP-43 and glutamate, which have been linked to the disease process in ALS. Furthermore, there seems to be evidence of inflammation.

Since the 1980s, there have been a number of  lab studies evaluating whether CSF from people with ALS (ALS-CSF) could be damaging to cells, but the results were variable and the overall effect unclear.

Now a team from the University of Edinburgh has analysed all previously published studies in a systematic way. The team was led by Dr Arpan Mehta, an MRC Lady Edith Wolfson Clinical Fellow based at the Euan MacDonald Centre and Anne Rowling Regenerative Neurology Clinic.

What did the study show?

The researchers found 28 studies to be eligible for analysis. The researchers found that a considerable majority of studies reported that ALS-CSF was damaging to cells. Most of the studies that did not show this finding dated from before 2000 when the technology was not as advanced as it is today.

It is still unclear why the CSF from people with ALS has this effect on cells. However, this new clear evidence of the phenomenon paves the way for future studies to assess the contribution of CSF to the MND disease process, with the aim of ultimately uncovering novel therapeutic targets.

It is intriguing to find that this effect of CSF can be consistently observed across studies, irrespective of study conditions such as CSF concentration, exposure time and the cell type involved. We believe that this is an important area for future research.

Dr Arpan Mehta

The study was funded by the MND Association and Medical Research Council.

Related links

Dr Arpan Mehta's profile (Anne Rowling Clinic website)

Link to the scientific publication: Cerebrospinal fluid cytotoxicity in amyotrophic lateral sclerosis: a systematic review of in vitro studies. Brain Communications, 2020. DOI: 10.1093/braincomms/fcaa121


This article was published on: Wednesday, August 05, 2020