• Demyelinating Diseases
• Neurology Clinical Trials

• Demyelinating Diseases
• Neurology Clinical Trials
• Neurology

In patients with relapsing-remitting multiple sclerosis (RRMS), bimonthly injection with low-dose αB-crystallin (HspB5) resulted in a decrease in gadolinium-enhancing (Gd+) lesions and clinical relapses as compared with the placebo. Hans van Noort, PhD, Delta Crystallon, Leiden, the Netherlands, presented data from a randomized study [2011-00447536; van Noort JM et al. ACTRIMS/ECTRIMS 2014 (poster P082)] that evaluated HspB5 for the treatment of RRMS.

The oligodendrocytes of patients with MS have high levels of HspB5, a glial stress protein that initiates local anti-inflammatory, neuroprotective, and tolerogenic innate responses [van Noort JM et al. J Neuropathol Exp Neurol. 2010; Ousman SS et al. Nature. 2007]. However, interferon-gamma-secreting Th1 memory cells that target HspB5 exist [van Noort JM et al, Nature. 1995; Ousman SS et al. Nature. 2007; Bajramović JJ et al. J Immunol. 2000], which results in interferon-gamma-induced tissue damage [Bsibsi M et al. Acta Neuropathol. 2014]. In a previous Phase 1 study, administration of a single injection of HspB5 to healthy subjects led to an antigen-specific decrease in T-cell responses. The purpose of this study was to further evaluate low doses of HspB5 in patients with RRMS.

In this double-blind phase 2a trial, 32 patients with RRMS were randomly assigned in a 1:1:1:1 fashion to receive 7.5, 12.5, or 17.5 mg of HspB5 or placebo, with follow-up continuing until 48 weeks. HspB5 was administered as 3 bimonthly intravenous injections given at the beginning of the study (week 0), and at week 8 and week 16. At baseline, among the 4 study arms, the mean Extended Disability Severity Scale (EDSS) score ranged from 3.13 to 3.81, the mean number of relapses over the past 2 years from 1.75 to 2.25, and the mean time since the last relapse from 3.32 to 4.23 months.

In patients who received HspB5, there was a trend toward a decrease in Gd+ T1 lesions in all HspB5 arms, as determined by magnetic resonance imaging (MRI), with the 7.5-mg dose of HspB5 resulting in a significant reduction (P = .017) over 36 weeks. When the data from the 7.5-mg and 12.5-mg HspB5 groups were combined, the MRI lesion load decreased by 75% at 36 weeks (P = .0105; Figure 1) compared with the placebo. After the last dose of HspB5 administered at 16 weeks, the reduction in MRI lesion load continued for 20 weeks. In addition, there was a similar reduction in the frequency of clinical relapses over the 36 weeks among the treatment arms. All doses of HspB5 were safe and well tolerated.

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Figure 1.

Effect of HspB5 Injection on MRI Lesion Load in RRMS

HspB5, alpha B-crystallin; Gd+, gadolinium-enhancing; MRI, magnetic resonance imaging; RRMS, relapsing-remitting multiple sclerosis.Reproduced with permission from JM van Noort, MD.

In conclusion, the results of this trial suggest that low-dose HspB5 is safe and well tolerated and may be effective in reducing MRI lesions and clinical relapses in patients with RRMS.

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