SLS-005 (trehalose) for Sanfilippo Syndrome, OPMD, and SCA3
Trehalose, which is currently an investigational molecule, has been studied in prior phase 2 clinical studies in over 70 patients with two rare diseases and demonstrated a favorable safety profile and promising efficacy signal
Seelos is currently collaborating with Team Sanfilippo Foundation (TFS). Upon approval by the FDA, TFS will begin a Phase 2b/3 clinical trial in up to 20 patients with Sanfilippo syndrome with Seelos providing the clinical supply of trehalose.
- Sanfilippo syndrome (or MPS III) is an inherited monogenic lysosomal storage disorder divided into four subtypes
- Occurrence of 1 in every 70,000
- Progressive disorder, with life expectancy of 10–20 years
- Rare disorder
- PolyQ muscular disease caused by mutations in PABPN1 gene
- Orphan designation (US/EU)
- Fast track designation (US)
- Largest cluster among French in Quebec, Canada (1 in 1000)
- Additional clusters in Bukhara Jews of Israel and in Hispanics of New Mexico
Type 3 (SCA3)3
- SCA3 (or Machado-Joseph disease) is an autosomal dominant cerebellar ataxia (ADCA I) due to CAG repeat expansions in ataxin
- Adult-onset neurological PolyQ disease that begins between the ages of 20 and 50
- Orphan designation (US/EU)
- Most commonly affects individuals of Portuguese/ Azorean descent
- Lavery C, Hendriksz CJ, Jones SA. Mortality in patients with Sanfilippo syndrome. Orphanet Journal of Rare Diseases, 2017;12(1):168.
- Source: Oculopharyngeal Muscular Dystrophy. National Organization for Rare Disorders (NORD). Available at: https://rarediseases.org/rare-diseases/oculopharyngeal-muscular-dystrophy/. Accessed March 2019.
- Coutinho P, Andrade C. Autosomal dominant system degeneration in Portuguese families of the Azores Islands: a new genetic disorder involving cerebellar, pyramidal, extrapyramidal and spinal cord motor functions. Neurology. 1978;28 (7) 703- 709
About SLS-005 (Trehalose)
Trehalose is a low molecular weight disaccharide (0.342 kDa) that protects against pathological processes in cells
It has been shown to penetrate muscle and cross the blood brain barrier
Two U.S. patents for parental administration of trehalose exist for patients with OPMD and SCA3; both are expected to expire in 2033. In addition, Orphan Drug Designation for OPMD and SCA3 has been secured in the U.S. and in the EU
Trehalose Mechanism of Action
- Mayer AL, Higgins CB, Heitmeier MR, et al. SLC2A8 (GLUT8) is a mammalian trehalose transporter required for trehalose-induced autophagy. Scientific Reports. 6 (38586).
Available at: https://www.nature.com/articles/srep38586#f1 Accessed February 2019.
- Uchida K, Unuma K, Funakoshi T, et al. Activation of Master Autophagy Regulator TFEB During Systemic LPS Administration in the Cornea. Journal Toxicol Pathol. 2014;27(2):153–8.
Trehalose Reduced Storage of Unprocessed Macromolecules in Sanfilippo Syndrome
- Mauri V.. Trehalose-mediated enhancement of glycosaminoglycan degradation in the lysosomal storage disorder Mucopolysaccharidosis III. Inaugural-Dissertation zur Erlangung der Doktorwürde der Hohen Medizinischen Fakultät der Universität zu Köln. 2014. Available at: https://d-nb.info/1047324342/34 Accessed February 2019.