Low-dose maraviroc, an antiretroviral drug, attenuates the infiltration of T cells into the CNS and protects the nigrostriatum in hemiparkinsonian monkeys ncbi.nlm.nih.gov/labs/pmc/a...
"Abstract
Parkinson’s disease (PD) is the most common neurodegenerative movement disorder in humans. Despite intense investigation, no effective therapy is available to stop the progression of this disease. It is becoming clear that both innate and adaptive immune responses are active in PD. Accordingly, we have reported marked increase in RANTES (regulated on activation, normal T cell expressed and secreted) and eotaxin, chemokines that are involved in T cell trafficking, in vivo in the substantia nigra (SN) and the serum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated hemiparkinsonian monkeys. Since RANTES and eotaxin share a common receptor CCR5, we examined the efficacy of maraviroc, an inhibitor of CCR5 and an FDA-approved drug against HIV infection, in hemiparkinsonian rhesus monkeys. First, we found glial limitans injury, loss of GFAP immunostaining and infiltration of T cells across the endothelial monolayer in SN of hemiparkinsonian monkeys. However, oral administration of low dose of maraviroc protected glia limitans partially, maintained the integrity of endothelial monolayer, reduced the infiltration of T cells, attenuated neuroinflammation, and decreased α-synucleinopathy in the SN. Accordingly, maraviroc treatment also protected both the nigrostriatal axis and neurotransmitters, and improved motor functions in hemiparkinsonian monkeys. These results suggest that low-dose maraviroc and other CCR5 antagonists may be helpful for PD patients."
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" Monkeys displaying hemiparkinsonian symptoms 7 d after the first intracarotid injection were included in the study. Therefore, hemiparkinsonian monkeys were randomized and one group of hemiparkinsonian monkeys (n=4) were treated with maraviroc (1.0 mg/kg body wt/d) orally for 30 d through banana starting from 7 d of MPTP injection (Fig. 1). The control group of hemiparkinsonian monkeys (n=4) received only banana as vehicle."
This is an HIV antiretroviral. Cost is $500 and up monthly at the recommended dosage. Will check what dosage this trial amounts to for humans.
This drug is used for HIV. I know only what I have read this evening. But what about Montelukast? Better safety and more widely used and more accessible. Have you ruled that one out? And it can be taken with Ambroxol bc in Europe it is sometimes combined? Just wondering if the interest in this antiviral Maraviroc is because you have ruled out Montelukast and Ambroxol?
There is a huge noise to signal ratio of invalid versus valid studies. Valid studies that demonstrate improvement of the underlying Parkinson's disease condition are rare. Any such study gets my attention.
It is not a question of this substance versus some other substance. The question is what is the risk and cost/benefit situation for each substance independently.
I have not ruled out montelukast although I have some concern about adverse effects.
Understood and appreciated. There is a plethora of “anti inflammatory antioxidant” choices. Antiviral is a new target for me that is possibly exciting to use with the aforementioned anti inflammatory antioxidants.
Right here in the abstract. It blocks a receptor also used by the HIV virus but in this case used by the immune system as originally designed by evolution:
"Since RANTES and eotaxin share a common receptor CCR5, we examined the efficacy of maraviroc, an inhibitor of CCR5"
Despite the availability of many drugs offering symptomatic relief in Parkinson’s disease, there are no drugs available offering neuroprotective effect. Hence, it was decided to evaluate the neuroprotective effect of montelukast, an anti-inflammatory drug, in rotenone induced model of Parkinson’s disease in rats. Forty eight male wistar rats were randomly divided into three groups. Group 1: Vehicle control, Group 2: Montelukast 5 mg/kg, Group 3: Montelukast 10 mg/kg. All the groups received rotenone 2.5 mg/kg intraperitoneally for 10 days as a disease inducing agent. The study drug montelukast was administered to respective groups orally from day 11 to day 24. On day 25, 24 h after 14 days of study drug administration, the rats were subjected to open field test, rota rod test and catalepsy test. Brain samples of rats from each group were collected for Malondialdehyde(MDA), Glutathione(GSH) and TNFα analysis. In the open field test both the doses of montelukast showed significant increase in the locomotor activity and also decreased the immobility time compared to vehicle (p < 0.05). In rotarod test, montelukast 5 mg/kg and 10 mg/kg showed significant increase in the time to fall, compared to vehicle (p < 0.05). In catalepsy test, both doses of montelukast significantly decreased the retraction time compared to vehicle(p < 0.05). The brain MDA levels were decreased and GSH levels were found to be higher in the two montelukast groups compared to vehicle (p < 0.05). TNFα levels too were decreased significantly on montelukast administration. Montelukast showed potential neuroprotective effect by virtue of its anti-oxidant and anti-inflammatory actions."
Price has gone done quite a bit. It’s being used for long Covid also. Look up Dr Bruce Patterson. I take it…but stopped temporarily w pros and cons. My dose is too high for my sensitivity level.
Interestingly the corresponding author for this study, Kalipada Pahan, Ph.D., was also the lead investigator for the cinnamon study that I cited in my report on cinnamon.
price of Maraviroc has gone down significantly and is being used by doctors for long covid protocol also. The dose I’m taking is too high and working on lowering it. Trying to see if it helps w my cognitive decline and other CNS symptoms. It has helped w my IBD also.
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