Hookworm Treatment To Increase The Immune Response In Patients With MS Is A Promising Area Of Study

By Adriene Marshall

Promotion of hookworm infection may be an innovative future approach to improving immune response in patients with relapsing multiple sclerosis (MS), according to the results of a phase 2, randomized clinical trial.

Prior research has observed a milder disease course among MS patients who have been naturally infected with gastrointestinal helminths and other parasitic agents, compared with those who are uninfected. Infection with Necator americanus induces a T-helper cell response that prevents autoimmunity, the study authors wrote in JAMA Neurology.

This is the largest placebo-controlled trial of helminth therapy for MS,” lead author Cris S. Constantinescu, MD, PhD, professor at the Research Group in Clinical Neurology at the University of Nottingham (England), said in an interview. “It shows that hookworm induces regulatory T cells, which are cells that suppress inflammation. In our study, this was associated with a larger proportion of patients who develop no new MS lesions under hookworm treatment, compared with placebo. Although the effect of hookworm was modest, it may be sufficient for a group of people whose MS may not be overly aggressive, or who for various reasons may not wish or be suitable for conventional MS treatments. The side effect profile and general safety were very good.”

Credit: David Scharf / Science Source

Applying hookworm larvae to skin

This single-center study included patients with MS aged 18-64 years with relapsing remitting MS or secondary progressive MS with relapses and who were not on immunomodulatory treatment. Recent use of corticosteroids or any investigational treatments was among the exclusion criteria.

A total of 71 patients (mean age, 45 years; women, n = 50) were randomized to live infection with third-stage hookworm larvae manufactured according to regulatory protocol or placebo. In treatment patients, 25 larvae were pipetted onto a gauze pad and placed on the arm for more than 30 minutes. Application of the larvae to the skin mimics natural infection, the study authors noted. The gauze pads of placebo patient contained pharmacopoeial-grade water.

In-person follow-ups occurred at 2 weeks, 1 month, and every month from months 3 to 9 (the treatment period). At the end of the treatment period, patients were given mebendazole twice daily for 3 days to eliminate the parasitic infection. A final follow-up was scheduled for month 12 (3 months post infection). In addition to undergoing various laboratory tests and examination of feces to determine the presence of N. americanus eggs, patients submitted to MRI and neurologic assessments during follow-up visits.

The primary outcome for this study was number of new or enlarging T2 lesions at months 4-9. The secondary outcome was change at 9 months in the percentage of percentage of CD44+CD25highCD127neg T-regulatory cells in peripheral blood.

Thus, people with less aggressive MS are recruited into trials – which means that it is more difficult to use conventional outcome measures such as frequent MRI activity and new lesions.

Nuanced study results

A total of 66 patients completed the treatment phase of the study and 61 completed the 3-month postinfection follow-up. With regard to the primary outcome, the overall number of new or enlarging lesions for the hookworm and placebo groups was 154 versus 164, respectively, which was not a significant difference. However, a higher percentage of patients in the hookworm group (51%) versus the placebo group (28%) had no detectable MRI activity, which suggests a treatment effect, the researchers pointed out. None of the patients withdrew from the study because of adverse effects.

The researchers noted that the characteristics of patients with MS who participate in clinical trials have changed in recent years. “There is increased accessibility to diagnostic procedures and early treatment for people with MS, and therefore fewer patients with standard severity and clinical course of their MS are coming to clinical trials, in particular if a placebo arm is involved,” said Dr. Constantinescu. “Thus, people with less aggressive MS are recruited into trials – which means that it is more difficult to use conventional outcome measures such as frequent MRI activity and new lesions.”

On the secondary outcome, patients in the hookworm treatment group saw a significant increase in the percentage of CD4+CD25highCD127neg T cells at 9 months, compared with patients in the placebo group. “I think there is interest and opportunity for future, larger studies with more refined outcome measures,” Dr. Constantinescu said.