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Posted On: 09/12/2020 7:41:35 PM
Post# of 154064
Havasu,
It appears that CCR5 d32 is associated with a significantly increased risk of MS, as well as premature death for MS patients with d32.
It has been stated that leronlimab has many fewer side effects than maraviroc, as it allows normal binding of CCL3 and CCL4, but not CCL5/RANTES to CCR5. I am still searching for the information indicating intact CCL3 & 4 binding, but I have a suspicion that the normal physiologic function outside of CCL5 binding would play a role both fewer side effects generally and in mitigating MS without adverse effects.
Association of CCR5 Δ32 deletion with early death in multiple sclerosis
An increased frequency of 32-bp deletion allele was found to be associated with early death (P = 0.00005) and with a progressive reduction in the years of survival (onset to death). The death hazard ratio of CCR5 with deletion versus no deletion was 2.12, suggesting that MS patients with the 32-bp deletion have twice the mortality rate of patients with the normal genotype. This effect was more significant in females (hazard ratio 3.58). A strong association of the CCR5delta32 deletion with early death could serve as a prognostic marker for MS.
https://www.researchgate.net/publication/8360..._sclerosis
CCR5-delta 32 allele is associated with the risk of developing multiple sclerosis in the Iranian population
https://pubmed.ncbi.nlm.nih.gov/19479371/
Increase in CCR5 Delta32/Delta32 genotype in multiple sclerosis
Our results suggest that the lack of CCR5 does not protect from MS, but rather it may predispose to the chronic course of the disease. This would further imply that in view of the redundancy in the chemokine system, CCR5 ligands must be assumed to function through other closely related chemokine receptors.
https://pubmed.ncbi.nlm.nih.gov/15080861/
It appears that CCR5 d32 is associated with a significantly increased risk of MS, as well as premature death for MS patients with d32.
It has been stated that leronlimab has many fewer side effects than maraviroc, as it allows normal binding of CCL3 and CCL4, but not CCL5/RANTES to CCR5. I am still searching for the information indicating intact CCL3 & 4 binding, but I have a suspicion that the normal physiologic function outside of CCL5 binding would play a role both fewer side effects generally and in mitigating MS without adverse effects.
Association of CCR5 Δ32 deletion with early death in multiple sclerosis
An increased frequency of 32-bp deletion allele was found to be associated with early death (P = 0.00005) and with a progressive reduction in the years of survival (onset to death). The death hazard ratio of CCR5 with deletion versus no deletion was 2.12, suggesting that MS patients with the 32-bp deletion have twice the mortality rate of patients with the normal genotype. This effect was more significant in females (hazard ratio 3.58). A strong association of the CCR5delta32 deletion with early death could serve as a prognostic marker for MS.
https://www.researchgate.net/publication/8360..._sclerosis
CCR5-delta 32 allele is associated with the risk of developing multiple sclerosis in the Iranian population
https://pubmed.ncbi.nlm.nih.gov/19479371/
Increase in CCR5 Delta32/Delta32 genotype in multiple sclerosis
Our results suggest that the lack of CCR5 does not protect from MS, but rather it may predispose to the chronic course of the disease. This would further imply that in view of the redundancy in the chemokine system, CCR5 ligands must be assumed to function through other closely related chemokine receptors.
https://pubmed.ncbi.nlm.nih.gov/15080861/
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