Smell Test Might Help Predict if MS Treatments Are Working

A measure of the nose’s sensitivity to smell could be used to detect whether treatments for relapsing multiple sclerosis (MS) are working or not, a new study indicates.

The scientists noted that their results need to be validated through further study, but said the findings suggest that a smell test might be “a useful biomarker” for the efficacy of MS therapies.

Using a smell assessment is “especially attractive from a practical perspective as testing is cheap, easy, consuming a mere 10 minutes, and well tolerated by patients,” the team wrote, noting that potential tests could have “significant prognostic value.”

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The study, “Olfactory threshold predicts treatment response in relapsing multiple sclerosis,” was published in the Multiple Sclerosis Journal.

For most people with the neurodegenerative disease, MS is characterized by relapses — times when old symptoms rapidly worsen or new symptoms suddenly develop. There are numerous disease-modifying treatments (DMTs) available for relapsing MS, which have been proven to lessen the risk of relapses and delay the accumulation of disability.

But while such DMTs for MS have been shown in clinical trials to be overall effective, every patient is unique, and any one person may or may not respond to a given therapy. There currently is no easy way to tell whether or not a patient is responding to treatment other than waiting to see if the disease worsens.

“There is an urgent need for biomarkers enabling a reliable and easy evaluation of the impact of therapeutic interventions, ideally indicating not only an absence of signs of disease activity but rather a positive change,” the researchers wrote.

Now, a team of scientists in Austria tested whether olfactory threshold, or OT, might be useful for this purpose. OT is basically a test of how sensitive a person’s nose is to smells — a higher OT indicates that a person’s nose can detect smaller amounts of an odorant (a smelly substance).

Notably, OT has been shown to worsen in MS patients during times of active inflammation in the brain, but the measure is generally not affected in people with MS whose disease is stable.

The study enrolled 123 people with relapsing MS who were starting on a new DMT for the first time. The participants’ OT was assessed at three time points: at the study’s start, known as the baseline, and then again after three months and one year.

OT was measured with the “Sniffin’ Sticks test,” which involves giving a participant three identical-looking sticks, and having them identify the one that is laced with n-butanol, a substance that has a harsh, banana-like, alcoholic scent. Different sticks with different amounts of the odorant are used to identify the threshold where participants can no longer reliably smell the difference, allowing the calculation of OT.

Over the course of the study, just under half (48%) of the patients had a relapse. OT scores were significantly lower (worse) among patients who relapsed at the study’s start (4.75 vs 6.75), and also after three months (4.50 vs 7.38) and a year (5.75 vs 7.5).

Also of note, in the first three months of the study, median OT scores decreased, by 0.25 points, among patients who relapsed. By contrast, in patients who did not relapse, median OT scores increased by 0.5 points over the first three months.

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Statistical analyses demonstrated that OT scores at the study’s start and at three months and one year could significantly differentiate patients’ relapse risk. The change in OT scores over the study’s first three months also was significantly predictive of relapse risk.

“Higher OT scores assessed at baseline … as well as during the first year of DMT … were independently associated with a decrease in relapse risk with the strongest association found at [month three],” the researchers wrote.

The most potent predictor was found to be OT at three months after therapy initiation: patients with an OT score higher than 6.5 at this time were about 90% less likely to have a relapse over the year-long study. Similarly, an increase in the OT score of at least 0.5 over the first three months was associated with an approximately 90% reduced relapse risk.

“Relapse risk decreased nearly 10-fold by each point improvement” on smell assessments, the researchers wrote.

While scores from these smell tests at three months and one year also were significantly associated with brain lesions, clinical disease activity, and evidence of disease activity — relapse and/or disability progression — the researchers noted that the accuracy of OT-based prediction was “markedly lower” for identifying disability progression.

“The prediction of DMT response remains one of the biggest challenges in managing patients with [relapsing] MS, as it is the key for tailoring treatment according to the individual disease activity. Here, we show that OT is an independent predictor of DMT response defined by freedom of relapse,” the researchers concluded.

The team cautioned that this is a single, relatively small study, noting a need for further research to validate their findings.