Friday, December 8, 2017

Rapamycin at the 2017 ACR Annual Meeting in San Diego





I had written about Rapamycin recently as I had visited Easter Island [1]. Rapamycin is a macrolide, which is produced by the bacterium Streptomyces hygroscopicus; samples of this bacterium were taken from Easter Island. The name Rapamycin commemorates Easter Island as Rapa Nui (Great Rapa) is the Polynesian name of Easter Island.

I was surprised that I’ve found three abstracts on Rapamycin at the 2017 ACR Annual Meeting in San Diego.

Olivier Benveniste and colleagues [2] presented a study called [Abstract 5L]: “Rapamycin Vs. Placebo for the Treatment of Inclusion Body Myositis: Improvement of the 6 Min Walking Distance, a Functional Scale, the FVC and Muscle Quantitative MRI”. Conclusion: “Even if the primary endpoint was not reached, these first results showed coherent data in favor of rapamycin. …”

A Japanese group of scientists around Yo Ueda looked at Rapamycin and found, that arthritis in SKG mice can be ameliorated [3].

Earl Sands and colleagues yet looked at another interesting field [4]: “Initial Phase 2 Clinical Data of SEL-212 in Symptomatic Gout Patients: Monthly Dosing of a Pegylated Uricase (Pegsiticase) with Svp-Rapamycin Enables Sustained Reduction of Serum Uric Acid Levels By Mitigating Formation of Anti-Drug Antibodies”. Conclusion: “SEL-212 has been well-tolerated, and, unlike pegylated uricases alone, has mitigated immunogenicity, reduced flare rate and enabled repeated monthly dosing with sustained control of sUA levels in gout patients.”

The abstract of Thomas Winans and colleagues looked at [5]: “mTORC1 Blockade with Rapamycin and N-Acetylcysteine Reduces Anti-Phospholipid Antibody Levels in Controlled Clinical Trials of Patients with SLE”. Conclusion: “These ancillary studies suggest that rapamycin and NAC limit aPL production which should be included as an efficacy outcome in clinical trials of mTORC1 blockade in patients with SLE and APS.”

I thought that Rapamycin had its place in transplantation medicine, but now I see that Rapamycin will be useful in Rheumatology, too.

Links and References:
[2] Benveniste O, Hogrel JY, Annoussamy M, Bachasson D, Rigolet A, Servais L, Salem JE, Hervier B, Landon Cardinal O, Mariampillai K, hulot JS, Carlier P, Allenbach Y. Rapamycin Vs. Placebo for the Treatment of Inclusion Body Myositis: Improvement of the 6 Min Walking Distance, a Functional Scale, the FVC and Muscle Quantitative MRI [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/rapamycin-vs-placebo-for-the-treatment-of-inclusion-body-myositis-improvement-of-the-6-min-walking-distance-a-functional-scale-the-fvc-and-muscle-quantitative-mri/. Accessed December 7, 2017.
[3] Ueda Y, Okano T, Yamada H, Ichise Y, Naka I, Takahashi S, Sendo S, Akashi K, Onishi A, Saegusa J, Morinobu A. Inhibition of the Mechanistic Target of Rapamycin Pathway and Glutaminolysis Facilitates the Expansion of Myeloid-Derived Suppressor Cells and Synergistically Ameliorates Arthritis in SKG Mice [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/inhibition-of-the-mechanistic-target-of-rapamycin-pathway-and-glutaminolysis-facilitates-the-expansion-of-myeloid-derived-suppressor-cells-and-synergistically-ameliorates-arthritis-in-skg-mice/. Accessed December 7, 2017.
[4] Sands E, Kivitz AJ, DeHaan Ph.D. W, Johnston L, Kishimoto TK. Initial Phase 2 Clinical Data of SEL-212 in Symptomatic Gout Patients: Monthly Dosing of a Pegylated Uricase (Pegsiticase) with Svp-Rapamycin Enables Sustained Reduction of Serum Uric Acid Levels By Mitigating Formation of Anti-Drug Antibodies [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/initial-phase-2-clinical-data-of-sel-212-in-symptomatic-gout-patients-monthly-dosing-of-a-pegylated-uricase-pegsiticase-with-svp-rapamycin-enables-sustained-reduction-of-serum-uric-acid-levels-by-m/. Accessed December 7, 2017.
[5] Winans T, Kelly R, Lai ZW, Faraone S, Phillips PE, Banki K, Perl A. mTORC1 Blockade with Rapamycin and N-Acetylcysteine Reduces Anti-Phospholipid Antibody Levels in Controlled Clinical Trials of Patients with SLE [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/mtorc1-blockade-with-rapamycin-and-n-acetylcysteine-reduces-anti-phospholipid-antibody-levels-in-controlled-clinical-trials-of-patients-with-sle/. Accessed December 7, 2017.

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