#ECTRIMS2019 – Nerve Cell Damage May Be Evident Years Before Symptoms Are

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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neurofilament blood levels

Damage to nerve cells appears to occur years before people with multiple sclerosis (MS) begin to show symptoms and is evident in a likely biomarker, new data suggest.

Researchers found raised levels of neurofilament light chain (NfL), a protein associated with nerve cell damage, in blood samples collected six years before individuals were diagnosed with MS.

Kjetil Bjornevik, MD, PhD, with Harvard T.H. Chan School of Public Health in Boston, presented the data in a talk at the 35th congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), which concluded Sept. 13 in Stockholm.

The presentation was titled “Serum neurofilament light chain as a presymptomatic biomarker in multiple sclerosis.

Before the onset of MS symptoms, patients often show signs of the disease, largely unrecognized, while they are in what is called a presymptomatic or prodromal phase.

“Little is know about this [prodromal] phase, such as how long it is, and what happens during this phase,” Bjornevik said.

NfL, a protein associated with nerve cell damage, has been proposed as a biomarker of disease severity and treatment response in MS patients.

Researchers assessed whether measuring NfL blood levels could help identify people with early MS, and better determine if “NfL could be a biomarker of the presymptomatic phase,” Bjornevik said.

The team analyzed blood samples taken from 60 active-duty U.S. military personnel who were diagnosed with MS. The samples, stored in the Department of Defense Serum Repository, were collected before and after MS symptom onset. For each sample, researchers also analyzed blood samples from healthy people matched by age, sex, and ethnicity serving as controls.

A highly sensitive molecular assay, called the Simoa NF-light assay, was used. Results showed that, at a median of six years before MS onset, blood levels of NfL were already high compared to controls. This difference grew significantly as the time of clinical onset of MS became closer.

Serum “NfL [levels] increased closer to MS onset in presymptomatic patients,” Bjornevik said.

Researchers also found that an increase in NfL levels of 5 pg/mL or higher during the presymptomatic phase was associated with a median 7.5 times greater risk of developing MS.

These findings support theories that MS begins years before people start to show its first symptoms.

Serum “NfL levels in presymptomatic MS patients were elevated years before the first neurological symptoms, compared with the levels in age- and sex-matched controls,” Bjornevik said.

“MS may have a presymptomatic or prodromal phase lasting several years, and neuroaxonal damage may occur already during this phase,” he concluded.

Bjornevik noted that further details can be found in research he participated in. Its accompanying article was recently published in the journal JAMA Neurology, titled “Serum Neurofilament Light Chain Levels in Patients With Presymptomatic Multiple Sclerosis.

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