Spinal Muscular Atrophy Mouse Models Respond to CK-2127107

Cytokinetics’ next-generation fast skeletal troponin activator CK-2127107 improves muscle function in mouse models of spinal muscular atrophy (SMA), according to a preclinical trial study.

The findings were presented at the MDA Scientific Conference in Arlington, Virginia.

Cytokinetics and Astellas Pharma are developing CK-2127107 (CK-107) as a treatment for SMA and other conditions characterized by neuromuscular or non-neuromuscular dysfunction, muscular weakness, or muscle fatigue.

“These data support our ongoing Phase 2 clinical trial of CK-2127107 in adolescent and adult patients with SMA,” Fady I. Malik, MD, PhD, Cytokinetics’ executive vice president of research and development, said in a press release. “The increased muscle force at sub-maximal nerve stimulation frequencies in mice inform the potential for CK-2127107 to increase muscle function in patients living with motor neuron dysfunction.”

The objective of the preclinical study was to see if CK-2127107 could improve skeletal muscle function in two mouse models of SMA that exhibited nerve dysfunction, muscle atrophy and decreased muscle force. The level of disease severity was different in the two models.

Single and ascending doses of CK-2127107 improved muscle function in the mouse models, the researchers found.

CK-2127107 is an investigational drug candidate intended to slow the regulatory troponin complex’s rate of calcium release in fast skeletal muscles. The complex consists of three proteins integral to muscle contraction.

Cytokinetics is also conducting a Phase 1b study (NCT03065959) to assess CK-2127107’s impact on muscle fatigue in elderly people with mobility problems. The study will compare the drug’s impact, versus a placebo’s, on skeletal muscle fatigue.

Another clinical trial that is under way is a Phase 2, double-blind, randomized, placebo-controlled, multiple-dose (NCT02644668) study. It will evaluate two ascending doses of CK-2127107 in SMA patients. The objective of the trial, which is in the patient-recruitment stage, is to see whether CK-2127107 can improve skeletal muscle function and muscle fatigue in patients with SMA Types II-IV.

Another Phase 2 study (NCT02662582) is evaluating CK-2127107’s impact on physical functioning and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD).

Source: Spinal Muscular Atrophy Mouse Models Respond to CK-2127107 – SMA News Today

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