Targeting B cells

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Yesterday ProfG posted on off-label agents. This is topical as it is at the forefront of many peoples minds and they are the basis for a number of clininal trials that are planned or on-going

Here is a new review to read if interested. It looks at agents that may be used to target B cells within the plasma cells

Click here a free read for 50 days

Plasma cell and B cell-targeted treatments for use in advanced multiple sclerosis

DavidBaker Benjamin M.Jacobs Sharmilee Gnanapavan Klaus Schmierer Gavin Giovannoni

Highlights

•Peripheral B cell responses have been targeted to inhibit active/relapsing multiple sclerosis.

•Inhibition of advance (progressive) multiple sclerosis may be achieved by targeting B cell responses in the CNS.

•Agents exist that could be used to target such B cell responses and could be used to show benefit.

Abstract

There is increasing evidence that agents that target peripheral B cells and in some instances plasma cells can exhibit marked effects on relapsing multiple sclerosis. In addition, B cells, including plasma cells, within the central nervous system compartment are likely to play an important role in disease progression in both relapsing and progressive MS. However, current B cell-targeting antibodies may not inhibit these, because of poor penetration into the central nervous system and often oligoclonal bands of immunoglobulin persist within the cerebrospinal fluid despite immunotherapy. Through targeting B cells and plasma cells in the CNS, it may be possible to obtain additional benefit above simple peripheral depletion of B cells. As such there are a number of inhibitors of B cell function and B cell depleting agents that have been developed for myeloma and B cell leukaemia and lymphoma, which could potentially be used off-label or as an experimental treatment for advanced (progressive) MS.

Click here a free read for 50 days

Why was this written? Well people wanted to know what could be done to get rid of B cells.

Thalidomide came up.

Would you run a mile based on the baggage that is attached to this drug or would you be willing to give it a go? It you were told that it was there to try and get rid of B cells in your brain.

Teriflunomide is damaging to the unborn but it is a standard MS drug.

There are alternatives that work in a similar way. If the drug had a different name than thalidomide would this make a difference?

Although, I perhaps should keep my mouth shut, this effort was all in largely in vain as people didn’t get the context. They prefer their own preference, I didn’t put up enough of a fight to keep them on the agenda.

Why?

Because pharma is in this space and they will frankly do it better and they will get on an do it rather than talk about doing it.

The Bruton Tyrosine kinase inhibitor has already been reported by Merck and the Genzyme Sanofi study of the CNS penetrant variant will be finished by the end of the year (NCT03889639).

The Proteosome inhibitor (NCT03783416) is ready to go.

Would you go for a CNS active TNF inhibitor like the thalimiomide type drugs. These will destroy B cell follicles. It has been seen in arthritis.

However the people involved in the PPI group did not want it.

However, it may not be a direct neuroprotective, I think MD2 looked at that already along with a few ion channel inhibitors.

I have even heard of people planning to do CAR-T…….Yikes. If it is not reversible..scary.

About the author

MouseDoctor

3 comments

  • And this is why this blog is second to none when it comes to keeping the MS and research community informed. These papers are typically tied up behind paywalls (I have a huge bug in my ass about this issue). Thanks MD and team. Knowledge is power, especially when deciding on treatments and dealing with the health service.

    To the question posed in your blog; yes, i’d have no problems with trialling thalidomide in MS if the evidence suggests it’s worth looking at. It is used to treat myeloma and the risks associated with the drug can be (mostly) mitigated (like alemtuzumab). Perhaps it’s time to move away from the paternalistic approach to treatment and allow pwMS decide what level of risk they are comfortable with. My gut tells me they’ll take the risks associated with treatment over the risks of poorly controlled / progressive MS all day long.

    Also, thanks for the review on the function of myelin. Most appreciated.

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