Graves' Disease Drug Development

The treatment of patients with Graves' disease (GD) has not changed substantially for many years, but great changes are on the horizon. The treatment of GD in the future will most likely involve monoclonal antibodies or small molecules. With extensive experience in drug development, Creative Biolabs has established a comprehensive platform to provide global customers with reliable cell-based therapy and antibody-development services.

Introduction to Graves' Disease

Graves' disease (GD), also known as von Basedow disease, is a syndrome characterized by an enlarged and overactive thyroid gland (Graves' hyperthyroidism), ocular abnormalities (Graves' orbitopathy; GO), and localized dermopathy (pretibial myxoedema; PTM). GD is the most common cause of hyperthyroidism globally. Graves' hyperthyroidism was originally believed to be a result of excessive thyroid-stimulating hormone (TSH) secretion by the pituitary gland, but the discovery of TSH receptor (TSHR) autoantibodies in 1956 established GD as an autoimmune disease. These autoantibodies act as TSHR agonists and induce thyroid cells to secrete excess thyroid hormones, with which patients with GD most commonly present.

Pathogenesis of Graves’ hyperthyroidism. Fig.1 Pathogenesis of Graves' hyperthyroidism. (Davies, 2020)

Treatment of GD

The treatment of GD has not changed considerably in recent years but the application of conventional treatments has become more sophisticated. Although most patients try to avoid surgery, the replacement of subtotal thyroidectomy with total thyroidectomy has avoided the distressing cases of recurrence post-surgery. Radioiodine therapy has also decreased in popularity because of its inherent nature and the potential exacerbation of GO after treatment. Besides, popularity for the antithyroid drug methimazole (or carbimazole) has surged, especially given the issues of liver toxicity associated with the antithyroid drug propylthiouracil. However, in rare cases, methimazole can also cause agranulocytosis and birth defects. Therefore, the medical management of GD remains an area ripe for improvement.

Indeed, the novel and disease-specific treatments for thyroidal and extrathyroidal GD aim to primarily target the main autoantigens of the disease and/or molecules playing an important part within the immunological response. Future causally directed treatment of GD will most likely involve monoclonal antibodies or small molecules that block TSHR or block the stimulatory effect of TSHR autoantibodies. In this respect, a human anti-TSHR monoclonal antibody is being tested in a phase I trial in patients with GD and GO. Understanding the structure and function of TSHR autoantibodies and the control of the immune response to the TSHR antigen is vital to gain further insight into their biological action and to the rational design of novel therapeutics.

Emerging therapies for GD. Fig.2 Emerging therapies for GD. (Davies, 2020)

Services at Creative Biolabs

Committed to drug development of the autoimmune disease, Creative Biolabs, an industry-leading biopharmaceutical company, has thrown in a great deal of manpower, materials, and financial resource to the research of the autoimmune disease, and thus established an advanced platform with the latest technologies, high-degree specialists, and mature technicians. With all these advantages, we are capable of providing high-quality drug development services including:

  • Monoclonal Antibody Development for GD
  • Bispecific Antibody Development for GD
  • Cell-based Therapy for GD

The novel therapeutic strategies of GD are under exploration and need more effort from researchers. Creative Biolabs has been focusing on the drug development of autoimmune disease for a long time. With extensive experience, we are eager to support global researchers in GD therapeutic strategies development. If you have any other questions, please feel free to contact us for more information.

Reference

  1. Davies, T. F.; et al. Graves' disease. Nat Rev Dis Primers. 2020, 6(1): 52.

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