PENDRED SYNDROME/DFNB4
■Principal investigators
Masato Fujioka, Makoto Hosoya / Department of Otorhinolaryngology, Keio University School of Medicine
EXPECTED THERAPEUTIC MECHANISM
Pendred syndrome was named after Dr. Vaughan Pendred, who reported its occurrence in a family in The Lancet in 1896. This rare disease—an autosomal recessive disorder with primary symptoms of dizziness, hearing loss, and goiter—affects approximately 4,000 individuals in Japan today. Basic research using induced pluripotent stem (iPS) cells derived from affected patients has discovered that diseased cells are frequently associated with intracellular protein aggregate formation, making them vulnerable to cellular stress. Moreover, sirolimus has been found to counteract this vulnerability in screening assays of existing compounds. The drug is believed to exert its therapeutic effects by promoting autophagy, since its effects are canceled out by the inhibition of the mTOR-dependent autophagy pathway.
SIROLIMUS’ EFFECTS IN PENDRED SYNDROME/ROADMAP TO COMMERCIALIZATION
We performed a phase I/IIa double-blind parallel-group single-institute trial of low-dose sirolimus for Pendred syndrome/DFNB4 at Keio University Hospital (PENDLRA trial: KCTR-D012, UMIN000033083), the results of which are currently being analyzed.
STATUS OF CLINICAL TRIALS
| Trial name | Category | Subjects | Dosage form |
|---|---|---|---|
| Parallel-group phase I/IIa trial (PENDLRA trial) | Physician-led clinical trial | Children/Adults | Tablet |
RELATED LINKS/TRIAL INFORMATION
■Research Overview | Keio University School of Medicine, Department of Otorhinolaryngology
http://www.ent.med.keio.ac.jp/news/20190116.html
■UMIN Clinical Trials Registry (UMIN-CTR)
https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000037719