Lead Inventors:
Richard B. Robinson, Ph.D.,
Michael R. Rosen, M.D.,
Ira Cohen, M.D.,
Peter Brink, Ph.D.
Biological Pacemaker Can Be Maintained Indefinitely
Cardiac arrhythmias affect 3 million Americans and account for nearly half a million deaths each year. Many arrhythmias are caused by failures in pacemaker activity or poor conduction of electrical impulses. Current methods for treating arrhythmias attempt to suppress arrhythmias with drugs, by ablating small areas or by implanting pacemaker devices. Antiarrhythmic drugs can create new arrhythmias while suppressing others. Ablation is successful mainly in a subset of simpler arrhythmias where a specific area can be targeted. Pacemakers can offer extended relief but must be maintained surgically and involve increased risk of infection and pulmonary collapse. An ideal solution would be to biologically create or restore a set of pacemaker cells to create a new pacemaker that could be introduced into the heart and maintained indefinitely.
Creating A Biological Pacemaker by Culturing the Patient's Chimeric HCN Cells
This invention is the vectors, methods, and sequences for creating biological pacemakers using wild type or chimeric forms of the Hyperpolarization-activated, Cycilic Nucleotide-gated (HCN) family of ion channels. After studying the dynamics of gating, polarization, and depolarization in each of the HCN family members, a group of chimeras was created that possessed faster kinetics, more positive activation, increased expression, increased stability, enhanced cAMP responsiveness, and enhanced neurohumal response. The mutant forms of HCN can be expressed in a cardiac cell to give it pacemaker functions more readily than expression of the WT forms. Effective pacemaker cells can be created by expressing the wild type or chimeric forms of HCN to yield a cell that is effective to cause the subject's heart to beat. The cells used to create pacemaker cells can be extracted from the patient and altered in culture, so that an immune response is not elicited. The pacemaker cells can be injected into a specific area of the heart such as the sinoatrial node or His branch, depending on the nature of the patient's arrhythmia. The forms of chimeric HCN can also be tailored to the site of injection so that the cells elicit a response at a certain voltage or with kinetics specific to that site.
Applications:
• Treatment of arrhythmias
• Improved pacemaker function
Advantages:
• Wide range of pacemaker responsiveness
• Can be created from autologous tissue avoiding rejection
• Can be tailored to specific heart problems
• Can work in conjunction with electronic pacemaker to give biventricular pacing
• Vectors and proteins can also be used in pharmaceuticals compositions
Patent Status: Patent Pending
Licensing Status: Available for Licensing and Sponsored Research Support
Publications: Bucchi A, Plotnikov AN, Shlapakova I, Danilo P Jr, Kryukova Y, Qu J, Lu Z, Liu H, Pan Z, Potapova I, KenKnight B, Girouard S, Cohen IS, Brink PR, Robinson RB, Rosen MR. Wild-type and mutant HCN channels in a tandem biological-electronic cardiac pacemaker. 2006.
Circulation. 5;114(10):992-9.