I ran across the following article today and found it interesting. It's about an older drug called fasudil that might possibly be used in the near future to help keep platelet counts normal while patients are on treatments like Revlimid or Velcade.
http://www.8newsnow.com/story/27408546/battling-multiple-myeloma
I found it particularly interesting because I'm currently taking 10 mg Revlimid every day (with no breaks) for my maintenance treatments. One of my doctors told me 1-2 weeks ago to switch to taking Revlimid 21 out of 28 days due to my WBC and platelet counts dropping. If there was a drug like Fasudil available, perhaps I could continue taking Revlimid 28 out of 28 days.
For others, this might allow them to continue taking a drug like Revlimid or Velcade rather than stopping them all together.
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DallasGG - Name: Kent
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: 6/20/2013
- Age at diagnosis: 56
Re: Fasudil - possible treatment for low platelet counts
Thanks for that information, Kent.
There's more information about this study available in this press release from the University of Utah,
"Discovery of Protein's Role in Making Platelets May Aid Multiple Myeloma Patients," Jul 27, 2014,
and in the original study itself,
DS Shi et al, "Proteasome function is required for platelet production," Journal of Clinical Investigation, Sep 2, 2014 (full text).
Abstract:
The proteasome inhibiter bortezomib has been successfully used to treat patients with relapsed multiple myeloma; however, many of these patients become thrombocytopenic, and it is not clear how the proteasome influences platelet production.
Here we determined that pharmacologic inhibition of proteasome activity blocks proplatelet formation in human and mouse megakaryocytes. We also found that megakaryocytes isolated from mice deficient for PSMC1, an essential subunit of the 26S proteasome, fail to produce proplatelets. Consistent with decreased proplatelet formation, mice lacking PSMC1 in platelets (Psmc1fl/fl Pf4-Cre mice) exhibited severe thrombocytopenia and died shortly after birth. The failure to produce proplatelets in proteasome-inhibited megakaryocytes was due to upregulation and hyperactivation of the small GTPase, RhoA, rather than NF-κB, as has been previously suggested.
Inhibition of RhoA or its downstream target, Rho-associated protein kinase (ROCK), restored megakaryocyte proplatelet formation in the setting of proteasome inhibition in vitro. Similarly, fasudil, a ROCK inhibitor used clinically to treat cerebral vasospasm, restored platelet counts in adult mice that were made thrombocytopenic by tamoxifen-induced suppression of proteasome activity in megakaryocytes and platelets (Psmc1fl/fl Pdgf-Cre-ER mice).
These results indicate that proteasome function is critical for thrombopoiesis, and suggest inhibition of RhoA signaling as a potential strategy to treat thrombocytopenia in bortezomib-treated multiple myeloma patients.
There's more information about this study available in this press release from the University of Utah,
"Discovery of Protein's Role in Making Platelets May Aid Multiple Myeloma Patients," Jul 27, 2014,
and in the original study itself,
DS Shi et al, "Proteasome function is required for platelet production," Journal of Clinical Investigation, Sep 2, 2014 (full text).
Abstract:
The proteasome inhibiter bortezomib has been successfully used to treat patients with relapsed multiple myeloma; however, many of these patients become thrombocytopenic, and it is not clear how the proteasome influences platelet production.
Here we determined that pharmacologic inhibition of proteasome activity blocks proplatelet formation in human and mouse megakaryocytes. We also found that megakaryocytes isolated from mice deficient for PSMC1, an essential subunit of the 26S proteasome, fail to produce proplatelets. Consistent with decreased proplatelet formation, mice lacking PSMC1 in platelets (Psmc1fl/fl Pf4-Cre mice) exhibited severe thrombocytopenia and died shortly after birth. The failure to produce proplatelets in proteasome-inhibited megakaryocytes was due to upregulation and hyperactivation of the small GTPase, RhoA, rather than NF-κB, as has been previously suggested.
Inhibition of RhoA or its downstream target, Rho-associated protein kinase (ROCK), restored megakaryocyte proplatelet formation in the setting of proteasome inhibition in vitro. Similarly, fasudil, a ROCK inhibitor used clinically to treat cerebral vasospasm, restored platelet counts in adult mice that were made thrombocytopenic by tamoxifen-induced suppression of proteasome activity in megakaryocytes and platelets (Psmc1fl/fl Pdgf-Cre-ER mice).
These results indicate that proteasome function is critical for thrombopoiesis, and suggest inhibition of RhoA signaling as a potential strategy to treat thrombocytopenia in bortezomib-treated multiple myeloma patients.
Re: Fasudil - possible treatment for low platelet counts
After I re-read the articles, I noticed it only mentioned bortezomib [Velcade]. I wonder if fasudil would also work with low platelet counts caused by Revlimid. I sort of assumed it wouldn't make any difference, but there might be something in the combination of fasudil and bortezomib (i.e., in the way bortezomib lowers platelet counts vs Revlimid) that only allows it to work with bortezomib. In any case, hopefully it will be good news for people taking bortezomib.
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DallasGG - Name: Kent
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: 6/20/2013
- Age at diagnosis: 56
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