5 ms·

Isn't Rapamycin generally used as part of an immunosuppressant cocktail for organ transplants? Curious why that isn't mentioned in the article as a contributin

by jhales 5y ago

Isn't Rapamycin generally used as part of an immunosuppressant cocktail for organ transplants? Curious why that isn't mentioned in the article as a contributing factor.

klevertree 5y ago
I thought it'd be too much in the weeds. The UTexas paper goes into their prescribing data and comes out with the conclusion that calcineurin inhibitors are the only common factor in their patients who don't get dementia. Rapamycin also does not have any evidence of efficacy on neurodegeneration, while there's evidence for CNI on other forms of neurodegeneration.
- TedDoesntTalk 5y ago
  What are the side-effects of calcineurin inhibitors ?
  - gzer0 5y ago
    Cyclosporine has some very serious long-term toxicity (especially renal dysfunction and hypertension) and the availability of newer biologic agents has restricted the use of cyclosporine to patients who have not responded to conventional treatment. *Mild tremor is common with both cyclosporine and tacrolimus use, occurring in 35 to 55 percent of patients [ 79,80 ]. *Rarely, patients develop severe headache, visual abnormalities, and seizures. This syndrome is associated with acute hypertension and resembles hypertensive encephalopathy [ 77 ]. *Posterior leukoencephalopathy is usually seen on brain imaging [ 82 ]. *Cyclosporine may contribute to bone loss after organ transplantation [ 88 ]; this effect may be due to the induction of high bone turnover. *Cyclosporine can cause hyperkalemia and hypomagnesemia, via effects on renal tubular function. Hyperuricemia and exacerbation of gout are well-described with cyclosporine. [77]. Schwartz RB, Bravo SM, Klufas RA, et al. Cyclosporine neurotoxicity and its relationship to hypertensive encephalopathy: CT and MR findings in 16 cases. AJR Am J Roentgenol 1995; 165:627. [78]. Eidelman BH, Abu-Elmagd K, Wilson J, et al. Neurologic complications of FK 506. Transplant Proc 1991; 23:3175. [79]. Randomised trial comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. European FK506 Multicentre Liver Study Group. Lancet 1994; 344:423. [80]. A comparison of tacrolimus (FK 506) and cyclosporine for immunosuppression in liver transplantation. The U.S. Multicenter FK506 Liver Study Group. N Engl J Med 1994; 331:1110. [81]. Wijdicks EF, Wiesner RH, Krom RA. Neurotoxicity in liver transplant recipients with cyclosporine immunosuppression. Neurology 1995; 45:1962.
aaron695 5y ago
Yes, given Rapamycin is taken by people for longevity I'm not sure why it's not mentioned or you were downvoted given the top comment is some bike shedding naturalism about the species on earth being wiped out. HN at it's core Obviously any longevity drug will help with dementia, else it's not a longevity drug. And Rapamycin has been looked at for dementia. There might be evidence it might make it worse if you already have dementia. This seems like a ok round up -https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Rapamycin-Cognitive-Vitality-For-Researchers.pdf https://www.alzdiscovery.org/uploads/cognitive_vitality_medi...

by jhales 5y ago

Isn't Rapamycin generally used as part of an immunosuppressant cocktail for organ transplants? Curious why that isn't mentioned in the article as a contributing factor.

klevertree 5y ago

I thought it'd be too much in the weeds. The UTexas paper goes into their prescribing data and comes out with the conclusion that calcineurin inhibitors are the only common factor in their patients who don't get dementia. Rapamycin also does not have any evidence of efficacy on neurodegeneration, while there's evidence for CNI on other forms of neurodegeneration.

TedDoesntTalk 5y ago
What are the side-effects of calcineurin inhibitors ?
- gzer0 5y ago
  Cyclosporine has some very serious long-term toxicity (especially renal dysfunction and hypertension) and the availability of newer biologic agents has restricted the use of cyclosporine to patients who have not responded to conventional treatment. *Mild tremor is common with both cyclosporine and tacrolimus use, occurring in 35 to 55 percent of patients [ 79,80 ]. *Rarely, patients develop severe headache, visual abnormalities, and seizures. This syndrome is associated with acute hypertension and resembles hypertensive encephalopathy [ 77 ]. *Posterior leukoencephalopathy is usually seen on brain imaging [ 82 ]. *Cyclosporine may contribute to bone loss after organ transplantation [ 88 ]; this effect may be due to the induction of high bone turnover. *Cyclosporine can cause hyperkalemia and hypomagnesemia, via effects on renal tubular function. Hyperuricemia and exacerbation of gout are well-described with cyclosporine. [77]. Schwartz RB, Bravo SM, Klufas RA, et al. Cyclosporine neurotoxicity and its relationship to hypertensive encephalopathy: CT and MR findings in 16 cases. AJR Am J Roentgenol 1995; 165:627. [78]. Eidelman BH, Abu-Elmagd K, Wilson J, et al. Neurologic complications of FK 506. Transplant Proc 1991; 23:3175. [79]. Randomised trial comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. European FK506 Multicentre Liver Study Group. Lancet 1994; 344:423. [80]. A comparison of tacrolimus (FK 506) and cyclosporine for immunosuppression in liver transplantation. The U.S. Multicenter FK506 Liver Study Group. N Engl J Med 1994; 331:1110. [81]. Wijdicks EF, Wiesner RH, Krom RA. Neurotoxicity in liver transplant recipients with cyclosporine immunosuppression. Neurology 1995; 45:1962.

aaron695 5y ago

Yes, given Rapamycin is taken by people for longevity I'm not sure why it's not mentioned or you were downvoted given the top comment is some bike shedding naturalism about the species on earth being wiped out. HN at it's core Obviously any longevity drug will help with dementia, else it's not a longevity drug. And Rapamycin has been looked at for dementia. There might be evidence it might make it worse if you already have dementia. This seems like a ok round up -https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Rapamycin-Cognitive-Vitality-For-Researchers.pdf https://www.alzdiscovery.org/uploads/cognitive_vitality_medi...