Helminth immune therapy for MS not up to scratch

Multiple sclerosis

By Mardi Chapman

16 Jun 2020

Hookworms might have missed their chance as a potential immunomodulatory treatment for MS.

Although the ‘evolutionary old friends’ have been shown to be well tolerated and have some favourable effects in a number of studies – in MS as well as other immune-mediated conditions such as coeliac disease – they’ve yet to wriggle beyond the research setting.

A phase 2 study just published in JAMA Neurology compared outcomes in 63 patients with relapsing remitting MS randomised to either N americanus larvae or placebo administered transcutaneously.

The UK study found that after nine months of treatment, the primary outcome of new or enlarging T2 lesions or newly enhancing lesions on MRI was not significantly different between the two groups of patients.

However there was a higher proportion of MRIs indicating no new activity in the treated group than the controls (51.4% v 27.8%) which the authors said suggested a beneficial effect.

A secondary outcome of the proportion of regulatory T cells in peripheral blood showed a numerical but not statistically significant increase in the treated group (4.4% v 3.9%).

Adverse events including diarrhoea, skin reactions at site and infections were similar in both patient groups (50.2% v 49.8%) although there were more site reactions with hookworms than placebo.

The authors said their findings demonstrated the feasibility and safety of controlled hookworm infection in MS.

“If the biological effect and the induced immunoregulatory mechanisms can be more efficiently harnessed, it may enhance therapeutic opportunities in MS, making this inexpensive, long-lived treatment potentially beneficial.”

However an accompanying editorial said the results should be interpreted cautiously.

“The effect on the immune profile is interesting; however, this finding cannot be translated to evidence of clinical efficacy.”

And importantly, MS treatments have moved on making future trials an ethical challenge.

“Comparing helminth therapy with placebo was reasonable when this study was initiated in 2011 but would be difficult to justify today given the availability of robustly effective immunomodulatory therapies,” it said.

“Conducting a trial with an active comparator group also would be difficult, as the efficacy of even the lowest potency available disease-modifying agents rival the effect of helminth treatment.”

It said the hygiene hypothesis associated with dysregulation of the immune system may still be important in preventing autoimmune disease but helminth therapy for MS was unlikely.

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