Rock inhibitors in SCI

[LukeTheDuke]

Why are there no clinical trials with Rock inhibitors in SCI?

There are plenty of Rock inhibitors and some are/ were in clinical trials for other indications

• https://en.wikipedia.org/wiki/Rho_kinase_inhibitor
• https://clinicaltrials.gov/ct2/show/NCT03792490
• https://clinicaltrials.gov/ct2/show/...&draw=2&rank=4

and there is a lot of evidence that Rock inhibition might be useful in SCI

• https://www.sciencedirect.com/scienc...63725818300561
• https://www.sciencedirect.com/scienc...168?via%3Dihub
• https://link.springer.com/article/10...596-016-1537-3

[paolocipolla]

Google "Cethrin" and you will find some info such as this: https://www.ncbi.nlm.nih.gov/pubmed/21381984

As far as I understand RHO inhibitors may help just in acute SCI.

Paolo

[LukeTheDuke]

Thanks, Paolo!

I agree that the halt of the Cethrin trial in phase IIb could indicate that Rock (Rho kinase) inhibitors might not work neither. However, Cethrin is a (derivative of a) bacterial enzyme that inhibits Rho through covalent modification. With a different mechanism of action -- as small molecule Rock inhibitors have -- the biological effect could be very different.

In my opinion it would not even be too difficult to evaluate this:

• The drug exist and should be safe in humans (otherwise there would not be phase II clinical trials with it)
• The SCI animal models exist and shown to be working for Rock inhibitors

Any ideas how to reach out to someone who could investigate this and would have an interest in doing so?

[paolocipolla]

Thanks, Paolo!

I agree that the halt of the Cethrin trial in phase IIb could indicate that Rock (Rho kinase) inhibitors might not work neither. However, Cethrin is a (derivative of a) bacterial enzyme that inhibits Rho through covalent modification. With a different mechanism of action -- as small molecule Rock inhibitors have -- the biological effect could be very different.

In my opinion it would not even be too difficult to evaluate this:

• The drug exist and should be safe in humans (otherwise there would not be phase II clinical trials with it)
• The SCI animal models exist and shown to be working for Rock inhibitors

Any ideas how to reach out to someone who could investigate this and would have an interest in doing so?

Ck this out: https://twitter.com/brettjhilton

He just pinned a tweet about RHO.

I never really digged into this line of research, it was hot many years ago... You may want to cantact Lisa McKerracher to hear her side of the story.

Could you point me to some SCI animal models that have shown to be working for Rock inhibitors, especially on chronic models of SCI?

Paolo

[LukeTheDuke]

I would start with the following papers:

• https://www.ncbi.nlm.nih.gov/pubmed/12151536
• https://www.ncbi.nlm.nih.gov/pubmed/12598630
• https://www.ncbi.nlm.nih.gov/pubmed/16624299

Not sure it works for chronic SCI though

[LukeTheDuke]

Could you point me to some SCI animal models that have shown to be working for Rock inhibitors, especially on chronic models of SCI?

• https://www.ncbi.nlm.nih.gov/pubmed/12151536
• https://www.ncbi.nlm.nih.gov/pubmed/12598630
• https://www.ncbi.nlm.nih.gov/pubmed/16624299

I am not sure it works on chronic SCI though