Trial of Liraglutide in Wolfram Syndrome

Washington-University-School-of-MedicineDear Families:

We (Drs. White, Marshall, Urano, and Hershey) are excited to announce that we are now funded to perform a clinical trial of liraglutide (Victoza®; NovoNordisk) in Wolfram Syndrome.  Led by Drs. White and Marshall, this study will focus on the tolerability and safety of liraglutide and possible beneficial effects. We are inviting all participants over 10 years old in the Wolfram Research Clinic to participate in this study.  

Liraglutide is a compound that is a glucagon-like peptide-1 (GLP-1) receptor agonist; that is, it acts like the natural hormone GLP-1.  GLP-1 increases the release of insulin from the pancreas after a meal and slows down the digestion of the meal; this lowers blood sugars in people with type 2 diabetes.  Liraglutide is approved by the Food and Drug Administration (FDA) for use in adults and children older than 10 years old with type 2 diabetes.  In animal models of Wolfram syndrome, liraglutide has also been shown to slow the progression of diabetes, and possibly neurodegeneration.  It is not known if this is also true in people with Wolfram Syndrome.

Participation in this study would require injecting liraglutide once a day for 12 months.  Being on liraglutide will likely lower blood sugars and insulin doses, but it is unlikely to eliminate the need for insulin completely. In addition, evaluations of insulin secretion, vision, and an MRI would be conducted at the annual research clinic, and data would be shared between those two studies.  Participation in this study is voluntary, and you will be free not to participate or to stop participating at any time, and you will still be able to keep participating in the research clinic.

If you are interested in learning more about this study we will discuss it with you during your visit to the Wolfram Syndrome Research Clinic, or you can contact Dr. Neil White at (314) 286-1157 or Dr. Bess Marshall at (314) 454-6051, and we can discuss it with you further.  

Neil H. White, MD (314) 286-1157

Bess A. Marshall, MD (314) 454-6051

Fumihiko Urano, MD, Ph.D.

Tamara Hershey, PhD

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A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome

Publication: Nature.com | Publication Date: May 4, 2020

Authors: Jana Mahadevan, Shuntaro Morikawa, Takuya Yagi, Damien Abreu, Simin Lu, Kohsuke Kanekura, Cris M. Brown & Fumihiko Urano

Abstract

Endoplasmic reticulum (ER) stress-mediated cell death is an emerging target for human chronic disorders, including neurodegeneration and diabetes. However, there is currently no treatment for preventing ER stress-mediated cell death. Here, we show that mesencephalic astrocyte-derived neurotrophic factor (MANF), a neurotrophic factor secreted from ER stressed cells, prevents ER stress-mediated β cell death and enhances β cell proliferation in cell and mouse models of Wolfram syndrome, a prototype of ER disorders. Read more

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