Elevated GFAP Levels Linked to More Motor Impairment in SMA

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by Marisa Wexler MS |

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Higher levels of the glial fibrillary acidic protein (GFAP) in the fluid around the brain and spinal cord are associated with poorer motor function among people with spinal muscular atrophy (SMA), a new study reports.

These results indicate that cells called astrocytes are more active in advanced SMA, according to researchers. However, GFAP levels in SMA patients overall did not differ from levels in people without the disease, suggesting that this protein has limited utility as a biomarker in SMA patients.

The study, “Glial fibrillary acidic protein in cerebrospinal fluid of patients with spinal muscular atrophy,” was published in Annals of Clinical and Translational Neurology.

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The GFAP protein is a marker of activity for astrocytes, star-shaped cells in the nervous system that help to support neuronal function. Astrogliosis, a form of astrocyte activation in response to damage, has been reported to occur in the nervous systems of people with SMA.

Here, a team led by scientists in Germany tested whether measuring GFAP levels in the cerebrospinal fluid (CSF) — the liquid around the brain and spinal cord — might be a useful biomarker in SMA.

“The aim of this study was to evaluate GFAP concentration in CSF (cGFAP) as a biomarker for disease severity and treatment monitoring in patients with SMA,” the team wrote.

The study and its results

The analysis included CSF samples from 58 adults and 21 children with SMA. In the overall group, the median age was 31, 52% were female, almost all patients had either type 2 or 3 SMA, and none had been on treatment at the study’s start. CSF samples from 23 adults and seven children without SMA were also analyzed as controls.

Overall, GFAP levels in CSF did not significantly differ between SMA patients and controls without the disease. In both groups, GFAP levels tended to be higher in older individuals.

After making statistical adjustments to account for age, GFAP levels showed a significant negative correlation with motor function, measured by the Hammersmith Functional Motor Scale Expanded and the Revised Upper Limb Module. In other words, patients with higher GFAP levels in their CSF tended to have worse motor function.

The researchers noted that GFAP levels were generally higher in patients with type 2 SMA compared to those with type 3 disease and that levels of this protein were higher in patients who could not walk. These data overall support the idea that increased astrogliosis may be characteristic of more severe SMA, the researchers said.

The patients were treated with Spinraza (nusinersen), the first approved disease-modifying treatment for SMA, for up to 14 months. Additional CSF samples were collected and analyzed, but results showed no significant changes in GFAP levels after over a year on Spinraza.

The researchers noted that, while the change was not significant overall, GFAP levels in most patients decreased after starting on Spinraza, and the decrease was significant for a subset of patients who experienced marked improvements in motor function.

Noting that GFAP levels usually increase over time as a person ages, the researchers hypothesized “that there might be an attenuation of astrogliosis during [Spinraza] treatment also in our cohort.”

“GFAP concentration in CSF is not an outstanding biomarker in patients with long-standing SMA, but might support the hypothesis that [astrocyte] activation is involved in SMA pathology and may be modulated by [Spinraza] treatment,” the scientists concluded.

The team noted that another protein, called neurofilament light (NfL), was elevated in patients with type 1 SMA compared with controls. They speculated that NfL, a well-established marker of nerve damage, might hold more promise as a biomarker for SMA, and they called for further research.

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