Background

Autoimmune Polyglandular Syndrome type 1 (APS-1), also known as Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED), is a rare autosomal recessive condition which leads to devastating disease in children. APS-1 is caused by mutations in the autoimmune regulator gene (AIRE) which plays a key role in central tolerance mechanisms. Deficiency of AIRE function in medullary thymic epithelial cells (mTECs) results in the immune system launching an attack on numerous tissues and organs including the pancreas, intestine, stomach, thyroid, liver and skin. The clinical spectrum of APS-1 includes more than 20 different organ-specific autoimmune disorders and patients often present a combination of several manifestations at the same time.

The prevalence of APS-1 is estimated at 1:100,000 (Kahaly and Frommer, 2018). A high prevalence found among some geographical areas in certain populations including the Iranian Jews (1:9000), Sardinians (1:14,400), Finns (1:25,000), Norwegians (1:80,000) , and Irish (1:130,000).

Technology Overview

Researchers at The University of Sheffield have recently developed a gene therapy vector with the ability to mediate non-specific AIRE replacement in vivo and bring about a reduction of APS-1-related symptoms in C57/B6 AIRE-mutant mice when delivered via intrathymic injection (Almaghrabi et al 2020). They now plan to create and develop a patentable gene therapy vector with the ability to selectively restore AIRE function in mTECs and treat APS-1 patients via the IV route of administration.

Benefits

Treatment options for APS-1 are currently limited to symptomatic therapies and are complicated due to the multi-organ involvement. Treatments include hormone replacement therapy for endocrine disorders, antimicrobials for candidiasis, or immunosuppression for hepatitis and malabsorption. These have some serious adverse effects, for example immunosuppressive drugs may increase the occurrence of infection, sepsis and cancer.

Applications

Treatment of APS‑1

Opportunity

Seeking a development partner to help develop and optimise AIRE gene therapy for humans. In the first instance, funding for a technician for two years would significantly accelerate development towards the clinic.

AIRE Gene Therapy for APS1

IP Status

Seeking