Stem cell-based gene delivery for biological pacemakers

This technology is a method for creating a biological pacemaker using human mesenchymal stem cells (hMSCs) expressing ion channels that are critical for the proper impulse initiation of the heart.

Unmet Need: A pacemaker that can respond to physiological cues

Electronic pacemakers are the current treatment for symptomatic atrioventricular block or sinoatrial node dysfunction. Unfortunately, electronic pacemakers have a limited ability to modulate pacing in response to exercise or other physiological cues and various devices, such as metal detectors, have been reported to interfere with pacemaker function. Furthermore, there are serious medical risks, such as intercurrent infection, associated with the implementation of the device and battery replacement procedures.

The Technology: Mesenchymal stem cells as gene delivery vehicles for creating biological pacemakers

This technology uses hMSCs as gene delivery vectors for creating a biological pacemaker. Adult hMSCs are genetically modified to express ion channels that enable the pacemaker to mimic the healthy heart’s natural ability to generate and conduct electrical current. When implanted at precise locations in the heart, these hMSCs can restore proper impulse initiation and propagate the impulse to multiple heart chambers without any adverse effects.

This technology has been used to create catecholamine-responsive biological pacemakers in dogs that function stably for at least 6 weeks.

Applications:

• Biological pacemaker
• Treatment for heart block, sinoatrial node dysfunction, and congestive failure
• Myocardial repair
• Treatment for muscle diseases such as gastric motility disorder, muscle control disorders, hyperirritable bladder disorders
• Drug delivery using stem cells

Advantages:

• Does not require a battery or node replacement
• Adaptable to changes in physiological activity
• Reacts to emotions
• Creates a physiological rhythm for the life of the patient
• Decreases the risk of inflammation and infection

Lead Inventor:

Michael Rosen, M.D.

Patent Information:

Patent Status

Related Publications:

• Chauveau S, Anyukhovsky EP, Ben-Ari M, Naor S, Jiang YP, Danilo P Jr, Rahim T, Burke S, Qiu X, Potapova IA, Doronin SV, Brink PR, Binah O, Cohen IS, Rosen MR. “Induced pluripotent stem cell-derived cardiomyocytes provide in vivo biological pacemaker function” Circ Arrhythm Electrophysiol. 2017 May; 10(5): e004508.

• Shlapakova IN, Nearing BD, Lau DH, Boink GJ, Danilo P Jr, Kryukova Y, Robinson RB, Cohen IS, Rosen MR, Verrier RL. “Biological pacemakers in canines exhibit positive chronotropic response to emotional arousal” Heart Rhythm. 2010 Dec; 7(12): 1835-1840.

• Plotnikov AN, Shlapakova I, Szabolcs MJ, Danilo P Jr, Lorell BH, Potapova IA, Lu Z, Rosen AB, Mathias RT, Brink PR, Robinson RB, Cohen IS, Rosen MR. “Xenografted adult human mesenchymal stem cells provide a platform for sustained biological pacemaker function in canine heart” Circulation. 2007 Aug 14; 116(7): 706-713.

Tech Ventures Reference:

• IR 1352

• Licensing Contact: Jerry Kokoshka