Possible immunotherapy treatment for Graves disease

[diogenes]

This new paper in Thyroid describes using immunotherapy to alleviate Graves hyperthyroidism. Free access A possible useful start to alternatives to removing the t thyroid or carbimazole:

Thyroid Vol. 29, No. 7 Immunology, Autoimmunity, and Graves’ Ophthalmopathy

Antigen-Specific Immunotherapy with Thyrotropin Receptor Peptides in Graves' Hyperthyroidism: A Phase I Study

Simon H.S. Pearce, Colin Dayan, David C. Wraith, Kevin Barrell, Natalie Olive, Lotta Jansson, Terrie Walker-Smith, Christina Carnegie, Keith F. Martin, Kristien Boelaert, Jackie Gilbert, Claire E. Higham, Ilaria Muller, Robert D. Murray, Petros Perros, Salman Razvi, Bijay Vaidya, Florian Wernig, and George J. Kahaly

Published Online:17 Jul 2019doi.org/10.1089/thy.2019.0036

Abstract

Background: Graves' disease is one of the most common autoimmune conditions, but treatment remains imperfect. This study explores the first-in-human use of antigen-specific immunotherapy with a combination of two thyrotropin receptor (TSHR) peptides (termed ATX-GD-59) in Graves' hyperthyroidism.

Methods: Twelve participants (11 female) with previously untreated mild to moderate Graves' hyperthyroidism were enrolled in a Phase I open label trial to receive 10 doses of ATX-GD-59 administered intradermally over an 18-week period. Adverse events, tolerability, changes in serum free thyroid hormones, and TSHR autoantibodies were measured.

Results: Ten subjects received all 10 doses of ATX-GD-59, five (50%) of whom had free triiodothyronine within the reference interval by the 18-week visit. Two further subjects had improved free thyroid hormones by the end of the study (7/10 responders), whereas three subjects showed worsening thyrotoxicosis during the study. Serum TSHR autoantibody concentrations reduced during the study and correlated with changes in free thyroid hormones (r = 0.85, p = 0.002 for TSHR autoantibody vs. free triiodothyronine). Mild injection-site swelling and pain were the most common adverse events.

Conclusions: These preliminary data suggest that ATX-GD-59 is a safe and well-tolerated treatment. The improvement in free thyroid hormones in 70% of subjects receiving the medication suggests potential efficacy as a novel treatment for Graves' hyperthyroidism.

[Hidden]

Is that similar to desensitising to hay fever or bee sting allergy by giving tiny doses and gradually building up tolerance?

[diogenes Remembering in reply to Hidden]

No, it will be like cancer therapy, giving equal doses over a period.

[Hidden in reply to diogenes]

I think cancer therapy either specifically targets the cancer cells direct or stimulates the immune system to detect and destroy them.

So this treatment is targeting the specific immune cells that are reacting against the thyroid?

Sorry, have read the post several times but it's a bit beyond me.

I love to find out things. As a child I loved Kipling's Just So Stories, and my favourite character was the mongoose whose motto was "Run and find out"! The teachers either loved or hated me because I was always asking questions.

Haven't changed much

[TSH110]

If it works for Graves’ disease might something similar be developed for autoimmune hypothyroidism?

[diogenes Remembering in reply to TSH110]

Quite possibly this is also on the cards.

[TSH110 in reply to diogenes]

Fantastic news this might free future sufferers from the tyranny of T4 monotherapy.

I presume it is a lost cause if the thyroid tissues were effectively destroyed before diagnosis and treatment were initiated...unless after 30 years a new thyroid has grown. It sounds like a rare occurrence anyway.

What’s the time scale for this to go from current research to an actual treatment?

[diogenes Remembering in reply to TSH110]

To get such things in general se, if hey work, would take at least 5 yard. Safety, efficiacy through trials etc takes a long time to get through.

[diogenes Remembering in reply to TSH110]

Repeat: faulty keyboard. To get such things in general use, if they work, would take at least 5 years. Safety, efficiacy through trials etc takes a long time to get through.

[TSH110 in reply to diogenes]

Thanks I thought 5yrs + likely and I assume that is if it all goes well. Hope keyboard fixed soon.

[MiniMum97 in reply to diogenes]

Do you think 5 or more years from now before we might see this licensed for use? I have Graves’ disease and am being pushed to consider RAI or thyroidectomy both of which don’t seem like great options for me and don’t fix the underlying autoimmunity. This is looking really positive so far and I wonder whether I can hold out (presuming future trials produce positive results of course).....

[TSH110]

Full txt is here:

ncbi.nlm.nih.gov/pmc/articl...