Posted by Jeff Berk; BOLT International
Las Vegas Haiku:
Vegas, How it works –
Either you’re in on the joke,
or you are the joke.
I’m going to apologize ahead of time for doubling up on MS blogs. Here goes: “I’m sorry if you’re sick of reading MS blogs”. How was that? Did my sincerity come through the sarcasm?
Okay, on to business… BOLT just published Multiple Sclerosis Thought Leader Panel #14. This Panel highlights a series of interviews conducted with our experts in September, 2011. For this Panel we asked our Thought-Leaders to engage in a thought exercise with us. The purpose was to designate their “fantasy formulary”, comprised of the top seven therapeutics, currently in the development pipeline, which they want to see available for use in the prevention/treatment of multiple sclerosis. We allowed Panelists to choose the class of drug, a specific drug (if they had a preference), the unmet needs to be addressed and the benefits that they expected their choices to deliver. The panel’s responses are just as enlightening regarding what they would NOT put on their fantasy formularies. This is the second iteration of this exercise, and for comparison we include normalized results (see scoring explanation) from Multiple Sclerosis Thought leader Panel #11, published in June 2010.
So if you work on the Dark Side (meaning that you’re a pharmacrat) and are developing MS drugs, you’ll find all sorts of juicy tidbits on all of the usual suspects.
But then there were the really cool ideas that you (okay, that “I”) never heard of before (well, at least not for MS)… These are things that are a little too early to make the fantasy formulary per-se, but still have some legs to them. One of the approaches that really got my attention was the possibility of using mesenchymal neural stem cells as a CNS targeting mechanism for delivery of small molecule payloads. The idea is to attach a specific small molecule that would inhibit microglia to a patient’s non-placental derived stem cells; from skin, blood or marrow. The concept is the same as the antibody drug conjugates that are being developed for a whole host of tumors (see e.g. Adcetris; brentuximab vedotin, Seattle Genetics/Millennium, for Hodgkin’s). Here are comments from a couple of our MS Thought Leaders:
“It is already a commercial opportunity because there are some clinical trials going on with stem cells. So at this point they are using mesenchymal neural stem cells. This can be a little bit more involved not just giving stem cells. You can give stem cells and have them carry something to the CNS. You can have them carry a specific small molecule that would inhibit microglia, for example, because these cells, especially if you take neural stem cells, they would go to the CNS. So the idea behind the stem cells is not particularly to help regenerate, it is not that they are replacing cells from the CNS. They are cells that can hone to the CNS and that can actually immunomodulate on their own. And they can be used as a piggy-back for other molecules. Very interesting concept. What are some of the practical risks of this approach and can you comment at all on the cost effectiveness? So given those concerns, where in the treatment paradigm would this kind of approach fit, especially if you could deliver a totally different active agent? Right. Ideally, and we are talking here the best case scenario, if we can find a way to get those to work the advantage would be that they are far less toxic than anything we can give peripherally. And we can derive these cells from the patient’s own bone marrow or skin or blood even then they are much safer than anything we can exogenously give. So as you think to the future is the projected standard of care going to be to extract bone marrow early in an MS patient’s disease? Yeah, or even skin-that you can change the skin cells into stem cells or blood. So you can isolate stem cells from the blood, not necessarily bone marrow”.
“Mesenchymal stem cell transplantation is already started. So there are probably another 10 or 20 molecules being looked at but they are nowhere near human trials”.