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Novel Immunomodulator Safe and Tolerable in Pilot Study for ALS

Key findings

  • In a previous study in an animal model of ALS, the novel immunomodulator RNS60 slowed disease progression
  • This 23-week pilot clinical trial of RNS60 met its primary endpoints of safety and tolerability
  • No serious adverse events related to RNS60 occurred, and no participant withdrew due to drug-related adverse events
  • Four participants stayed on RNS60 through an extension phase for a total of 47 weeks of treatment

Amyotrophic lateral sclerosis (ALS) is now understood to be associated with neuroinflammation, and T cells are emerging as key players in the progression of the disease. The function of regulatory T cells (Tregs), which usually keep neuroinflammation in check, is suppressed and levels of FOXP3, a Treg transcription factor, are reduced.

RNS60, a novel immunomodulatory agent, has demonstrated protective properties in several laboratory and animal models of neurodegeneration. In a mouse model of ALS, treatment with RNS60 upregulated FOXP3-expressing Tregs and activated protective cells, which rescued motor neurons and slowed disease progression.

Researchers at Massachusetts General Hospital recently conducted a pilot clinical trial in which RNS60 proved feasible, safe and tolerable for people with ALS. Sabrina Paganoni, MD, PhD, and Nazem Atassi, MD, and colleagues from the Healy Center for ALS at Massachusetts General Hospital report the results in Muscle & Nerve.

Participants were enrolled in the open-label trial between October 2015 and February 2017. The inclusion criteria were deliberately broad for this pilot study: a diagnosis of possible, probable laboratory-supported, probable or definite ALS with no restrictions on disease duration, vital capacity or use of assisted ventilation or a feeding tube.

Of the 24 patients who volunteered for the study, six were excluded due to poor suitability for the type of brain imaging planned. Of the remaining patients, two out of 18 developed unrelated medical problems and withdrew prior to dosing, leaving 16 study participants.

RNS60 was administered by both weekly intravenous infusion and daily nebulization. Each participant made weekly in-person visits to the infusion center through week 23 (for a total of 24 infusions) and used nebulization at home on the other days of the week.

Participants who completed 23 weeks of treatment were offered the option of enrolling in an extension phase, remaining on RNS60 for a total of up to 47 weeks.

The trial met the primary endpoints of safety and tolerability. No serious treatment-related adverse events occurred, and no participant withdrew from the trial because of treatment-related adverse events.

Thirteen participants (81%) stayed on RNS60 for 23 weeks. Two withdrew due to disease progression and one moved away. There were no clinically significant changes in vital signs or standard laboratory tests. The average adherence rate was 99% for infusion visits and 96% for nebulization.

The study demonstrated the feasibility of longitudinal use of simultaneous magnetic resonance-positron emission tomography (MR-PET) brain imaging in ALS trials, using the radiotracer [11C]-PBR28. However, only nine participants had both pre- and post-treatment scans, and the study was underpowered to demonstrate significant imaging changes.

Similarly, there were no significant changes in blood biomarker assays (FOXP3 mRNA and interleukin-17), the ALS Functional Rating Scale-Revised or muscle strength analyses. The researchers suspect the small sample size contributed to these findings.

Mass General is now recruiting patients for a large, international, placebo-controlled phase 2 trial to evaluate how RNS60 affects ALS biomarkers and disease progression.

Learn more about the Sean M. Healey & AMG Center for ALS

Learn more about ALS research at Mass General


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