Mutation May Be Protective for Post-stroke Falls and Cognitive Decline

Older adults with greater variability in gait characteristics related to step length and walking speed are more likely to fall, especially after stroke. Recent evidence has suggested that C-C chemokine receptor 5 (CCR5), an established factor involved in immune processes and neuromodulation, may be a promising target for post-stroke recovery. In rodents, CCR5 knockdown was shown to promote motor recovery and increase axonal sprouting after stroke. In humans, post-stroke patients with the CCR5-Δ32 mutation have improved cognitive and motor recovery.

A newly published study by Molad and colleagues investigated the relationship between gait variability and CCR5-Δ32 carrier status. The findings are based on a large prospective cohort of post-stroke patients (Tel Aviv Brain Acute Stroke Cohort; TABASCO) with gait and NeuroTrax computerized cognitive assessment at admission, 6, 12, and 24 months. Analysis was for 335 patients with both gait and CCR5-Δ32 data. The researchers found lower variability and higher speed at 6 and 12 months for carriers vs. non-carriers, even after adjustment for age, gender, education, ethnicity, and stroke severity. This was also true when patients performed a dual (concurrent) task. Notably, lower stride time variability during the dual task was associated with better cognitive function, with a stronger correlation for CCR5-Δ32 carriers than non-carriers, who had higher variability and lower cognitive scores.

This study is the first to report that carriers of a naturally occurring loss-of-function mutation (CCR5-Δ32) show better gait at 6 and 12 months post-stroke that is similar to healthy older individuals. Greater gait variability among non-carriers may be a predictive marker for falls and cognitive decline. Indeed reciprocity between gait variability and cognitive scores suggests the presence of cognitive-motor interactions. The work builds on previous results from the same cohort showing a relationship of CCR5-Δ32 carrier status with cognitive deterioration and depression in humans, as well findings of a correlation with motor function in mice. The investigators posit that CCR5-Δ32 may be a promising molecular target for intervention by reducing inflammatory response. Recently, they initiated a phase 2 clinical trial to examine the safety and efficacy of Maraviroc, a CCR5 antagonist, in post-stroke cognitive impairment; NeuroTrax is an outcome.

Full text (open access):

Molad, J., Hallevi, H., Seyman, E., Rotschild, O., Bornstein, N.M., Tene, O., Giladi, N., Hausdorff, J.M., Mirelman, A., and Ben Assayag, E. (2022). CCR5-Δ32 polymorphism – a possible protective factor from gait impairment among post-stroke patients. European Journal of Neurology. PMID: 36380716