Why do we use IFN-α vs IFN-β? Might IFN-β be preferred?

[EPguy]

I've discussed IFN types before. Some interesting info here that INF-β might be better to reduce inflammation/progression.

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A recent post noted that Interferon is used for MS disease. This is the other IFN type 1, IFN-β (vs our IFN-α). I checked into why the difference. It turns out there is no really good reason we don’t use IFN-β. In fact there is a good argument that IFN-β might be a better therapy. See report here discussing some history and the IFNs.

IFN-α is PEG or Besremi. IFN-β is sold for MS as “Plegridy”. Very familiar note on pegylation from 2013:

“PLEGRIDY is a new molecular entity in which interferon beta-1a is pegylated to extend its half-life and prolong its exposure in the body, enabling study of a less frequent dosing schedule”

fiercebiotech.com/biotech/b...

Since Plegridy is approved for other use, we could theoretically try it esp if one has failed IFN-α as proposed below, but no Dr is likely to do such experiments outside trials.

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Report on IFN:

mdpi.com/2072-6694/14/22/5495

Some notes, quotes:

IFN-α recent revival: rIFN-α2 unfortunately disappeared in the dark. However, the interest in using rIFN-α2 in MPNs has been revived in recent years due to the mounting evidence from several studies within the last 5–10 years

-Several studies have shown IFN-B to possess stronger anticancer capabilities (for non- MPN cancers) than IFN α–2 (PEG, Bes)

-IFN-α has limitations re inflammation leading to non-response for some, IFN β has better anti-inflam properties: There are reasons to believe that the treatment of MPN patients with IFN- β may not only have the potential to normoregulate elevated blood cell counts, but also dampen the chronic inflammatory state that accompanies MPNs and likely contributes to clonal expansion and evolution.

-IFN- β exhibits better anti-inflammatory effects via several mechanisms: However, the much stronger binding of IFN-B to IFNAR1 (50-fold) and IFNAR2 (1000-fold) than that of IFN- α, along with the potent anti-inflammatory capacity of IFN-B, might theoretically diminish the impact of the inflammatory cytokines on IFN2AR1 degradation.

-IFN- β is used for breast cancer for good reason: Early studies in breast cancer cell lines showed IFN- β to be highly superior to IFN-a; accordingly, IFN- β was suggested for the treatment of all breast cancers.

-Combo therapies:

-Tamoxifen treatment blocked the development of JAK2V617F-induced myeloproliferative neoplasms in mice and induced apoptosis (death) of human JAK2V617F+ HSPCs in a xenograft model (usually human cells in mice)

-IFN-α alone acts on the mutation indirectly through the immune system, while: Since tamoxifen augmented the antiproliferative activity of IFN- β in vitro as well as in vivo [195], it was concluded that this combination might act directly on tumor cells rather than indirectly on the immune system. (IFN-α with tamoxifen is also a possibility)

-Another proposed combo: Combination Therapy of Tamoxifen, Retinoic Acid, and rIFN-B

-IFN-α is our best bet for now but: We can conclude that stem-cell targeted therapy with rIFN-a2 will be the cornerstone in the future treatment of MPN patients. Unfortunately, a large number of patients do not tolerate rIFN-a2 or are refractory to treatment. The novel rIFN-a2b Besremi seems to be less toxic and perhaps also more effective than treatment with Pegasys, which is the only alternative today. Therefore,we are in an urgent need of stem-cell-targeting drugs other than Besremi and Pegasys, (such as IFN- β)

-Studies of the safety and efficacy of rIFN- β in patients who are refractory or intolerant to rIFN-a2 might be highly important to determine whether rIFN- β might “rescue“ such patients…repurposing rIFN-B in the treatment of MPNs is expected to open a new horizon for MPN patients.

[KLCTJC]

thanks for posting this!!! I am the one with MS. I have gathered all of the information I can find and going to see what MD Anderson says when I go I. January. When I found out I had MS he said no Besremi, but I have found two articles that can argue that. MS doc said I have a benign version no meds right now but his choice is a beta intferon if I go on something. I will update everyone on what I find out in January. But I agree the two are very close in action. Thank you for this! I needed some reassurance that I was on to something

[EPguy in reply to KLCTJC]

Such great connections. If the current MPN thinking to IFN applies to MS, you want to act while it's "mild". But these may not be comparable.

As a min if you do get beta therapy seems quite possible you'll benefit on the MPN side. If you're on cytoreduction (HU etc) the added Beta might let you use less or none of it, good questions for Dr.

[MPort]

Thanks for this. It's great you do the research and we can learn about other possible treatment options.