Modified statin with muscle-friendly, lipid-lowering benefits

This technology is a modified statin molecule that reduces hypercholesterolemia while preventing muscle weakness, a common side effect of statin use.

Unmet Need: Statin-mediated hyperlipidemia treatment without muscle-related side effects

Statins reduce the risk of cardiovascular disease and are the primary pharmaceutical treatment for individuals with elevated low-density lipoprotein cholesterol. Muscle-related side effects, including weakness, are among the most common adverse effects of statin therapy and can lead to decreased patient adherence and reduced tolerable doses, thereby limiting treatment effectiveness against hypercholesterolemia. Statins primarily act by inhibiting the cholesterol-synthesizing enzyme HMG-CoA reductase, but they also interact with ryanodine receptors in muscle cells, which is hypothesized to contribute to muscle weakness. Therefore, there is a need for a statin that is equally effective at inhibiting HMG-CoA reductase and does not activate ryanodine receptors.

The Technology: Effective cholesterol-reducing statin with low ryanodine receptor binding

This technology is a modified statin that reduces circulating cholesterol but binds to ryanodine receptors on muscle cells less effectively, thereby preventing the development of muscle weakness. The statin structure has been modified to prevent interaction with ryanodine receptors while maintaining interaction with HMG-CoA reductase. Preserving the conserved HMG-CoA reductase binding ability retains the molecule’s efficacy in lowering cholesterol compared to existing statin therapies.

Applications:

• Treatment for cholesterol management
• Treatment for familial hypercholesterolemia
• Treatment for cardiovascular disease
• Treatment for chronic kidney disease
• Research tool for studying the effects of statin-activated ryanodine receptors on muscle weakness

Advantages:

• Decreases adverse muscle-related side effects
• Improves patient adherence to treatment plan
• Increases the tolerable dose of statin treatment

Lead Inventor:

Andrew Marks, M.D.

Patent Information:

Patent Pending

Related Publications:

• Weninger G, Dridi H, Reiken S, Yuan Q, Zhao N, Groom L, Leigh J, Liu Y, Tchagou C, Kang J, Chang A, Luna-Figueroa E, Miotto MC, Wronska A, Dirksen RT, Marks AR. “Structural basis for simvastatin-induced skeletal muscle weakness associated with type 1 ryanodine receptor T4709M mutation.” J Clin Invest. 2025 Dec 15; 135(24): e194490.

• des Georges A, Clarke OB, Zalk R, Yuan Q, Condon KJ, Grassucci RA, Hendrickson WA, Marks AR, Frank J. “Structural Basis for Gating and Activation of RyR1.” Cell. 2016 Sep 22; 167(1): 145-157.e17.

Tech Ventures Reference:

• IR CU24350

• Licensing Contact: Joan Martinez