Sigma non-opioid receptor 1 agonist for the treatment for Timothy Syndrome

This technology is a set of small molecule agonists of the Sigma non-opioid receptor for the treatment of Timothy Syndrome.

Unmet Need: Non-blood-brain-barrier permeable small molecule

Activation of Sigma non-opioid receptor 1 (SIGMAR1) may treat Timothy Syndrome. Current Sigma non-opioid receptor 1 agonists include dextromethorphan and fluovoxamine. However, these agonists were designed to treat neurological disorders and thus are highly permeable to the blood-brain barrier (BBB). High BBB permeability of SIGMAR1 agonists can produce undesired side effects for the treatment of Timothy Syndrome.

The Technology: Effective small molecule to treat Timothy Syndrome

This technology describes the development of small molecule SIGMAR1 agonists MY33-1 and MY33-2 that are “less permeable” through the blood-brain barrier (BBB) to treat Timothy Syndrome. These agonists rescue cardiac phenotypes in Timothy Syndrome stem cell models. Thus, MY33-1 and MY33-2 may be used to treat Timothy Syndrome and cardiac arrhythmias.

This technology has been tested in Timothy Syndrome patient-specific induced pluripotent stem cell models.

Applications:

• Research tool for studying cardiac arrhythmias
• Treatment for
  • Timothy Syndrome
  • Cardiac arrhythmias
  • Diseases related to aberrant calcium signaling

Advantages:

• Less permeable through blood-brain barrier
• More efficient
• Minimal side effects

Lead Inventor:

Masayuki Yazawa, Ph.D.

Patent Information:

Patent Pending

Related Publications:

• Song L, Bekdash R, Morikawa K, Quejada JR, Klein AD, Aina-Badejo D, Yoshida K, Yamamoto HE, Chalan A, Yang R, Patel A, Sirabella D, Lee TM, Joseph LC, Kawano F, Warren JS, Soni RK, Morrow JP, Yazawa M. Sigma non-opioid receptor 1 is a potential therapeutic target for long QT syndrome. Nat Cardiovasc Res. 2022 Feb; 1(2): 142-156.

• Song L, Park SE, Isseroff Y, Morikawa K, Yazawa M. Inhibition of CDK5 Alleviates the Cardiac Phenotypes in Timothy Syndrome. Stem Cell Reports. 2017 Jul 11; 9(1): 50-57.

Tech Ventures Reference:

• IR CU23081

• Licensing Contact: Kristin Neuman