Scientific Publications

MyoKardia Publications and Recent Presentations

PIONEER-HCM: A Phase 2 study of Mavacamten (formerly MYK-461) in Symptomatic Obstructive Hypertrophic Cardiomyopathy Patients
HFSA 2017 Presentation; Heitner et al; September 2017

In vivo Cardiac Effects of Mavacamten (MYK- 461): Evidence for Negative Inotropy and Improved Compliance
AHA Scientific Sessions 2017 Presentation; del Rio, et al; November 2017

Machine Learning Detection of Obstructive Hypertrophic Cardiomyopathy Using a Wearable Biosensor
AHA Scientific Sessions 2017; Green et al; November 2017

A Small Molecule Modulator of Cardiac Myosin Acts On Multiple Stages of the Myosin Chemomechanical Cycle
Journal of Biological Chemistry; Kawas et al; August 2017

A Novel Oral Myosin Modulator (MYK-461) for the Treatment of Obstructive Hypertrophic Cardiomyopathy: Initial Single Ascending Dose Data in Healthy Volunteers and Patients [PDF]
American Heart Association Scientific Sessions, 2016

A Small Molecule Inhibitor of Sarcomere Contractility Suppresses Hypertrophic Cardiomyopathy in Mice 
Science; Green, E.M. et al; February 2016

Genetic Cardiomyopathies

Hypertrophic and Dilated Cardiomyopathy: Four Decades of Basic Research on Muscle Lead to Potential Therapeutic Approaches to These Devastating Genetic Diseases
Biophysical Journal; Spudich, J. A.; March 2014

Understanding cardiomyopathy phenotypes based on the functional impact of mutations in the myosin motor
Circulation Research; Moore, JR et al; July 2012

Shared Genetic Causes of Cardiac Hypertrophy in Children and Adults
New England Journal of Medicine; Morita, H. et al; May 2008

Hypertrophic Cardiomyopathy

Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation
Proceedings of the National Academy of Sciences of the United States of America; J.R. Homburger et al; May 2016

Effects of Troponin T Cardiomyopathy Mutations on the Calcium Sensitivity of the Regulated Thin Filament and the Actomyosin Cross-bridge Kinetics of Human b-cardiac Myosin
PLoS One; Sommese, R.F. et al; December 2013

Allele-Specific Silencing of Mutant Myh6 Transcripts in Mice Suppresses Hypertrophic Cardiomyopathy
Science; Jiang, J. et al; October 2013

Molecular consequences of the R453C hypertrophic cardiomyopathy mutation on human β-cardiac myosin motor function
Proceedings of the National Academy of Sciences; Sommese, R. et al; July 2013

Cell-Intrinsic Functional Effects of the Cardiac Myosin Arg-403-Gln Mutation in Familial Hypertrophic Cardiomyopathy
Biophys J.; Chuan, P. et al; June 2012 

The Management of Hypertrophic Cardiomyopathy
New England Journal of Medicine; Spirito, P. et al; March 1997

Reducing Contractility Predicts Clinical Benefit in Obstructive HCM (oHCM)

Effect of Left Ventricular Outflow Tract Obstruction on Clinical Outcome in Hypertrophic Cardiomyopathy
The New England Journal of Medicine; Maron, M. et al; January 2003

Long-Term Effects of Surgical Septal Myectomy on Survival in Patients with Obstructive Hypertrophic Cardiomyopathy
Journal of the American College of Cardiology; Ommen, S. R. et al; August 2005

β Blockers for Prevention of Exercise-Induced Left Ventricular Outflow Tract Obstruction in Patients With Hypertrophic Cardiomyopathy
The American Journal of Cardiology; Nistri, S. et al; September 2012

Multicenter Study of the Efficacy and Safety of Disopyramide in Obstructive Hypertrophic Cardiomyopathy
Journal of the American College of Cardiology; Sherrid, M. et al; April 2005

Verapamil Therapy: A New Approach to the Pharmacologic Treatment of Hypertrophic Cardiomyopathy
Circulation; Rosing, D. et al; December 1979

Dilated Cardiomyopathy
The hypertrophic cardiomyopathy myosin mutation R453C alters ATP binding and hydrolysis of human cardiac β-myosin
J Biol Chem; Bloemink, M. et al; February 2014

Truncations of Titin Causing Dilated Cardiomyopathy
New England Journal of Medicine; Herman, D. et al; February 2012

Mutations in Sarcomere Protein Genes as a Cause of Dilated Cardiomyopathy
New England Journal of Medicine; Kamisago, M. et al; December 2000

Motor System Reviews
One Path to Understanding Energy Transduction in Biological Systems
NatMed; Spudich, J.A.; October 2012

Molecular Motors: Forty Years of Interdisciplinary Research
Mol Biol Cell; Spudich, J.A.; November 2011

Foundational Research
The superfast human extraocular myosin is kinetically distinct from the fast skeletal IIa, IIb, and IId isoforms
J Biol Chem; Bloemink, M.J. et al; September 2013

Identification of functional differences between recombinant human α and β cardiac myosin motors
Cell Mol Life Sci; Deacon, J.C. et al; July 2012

Effects of pathogenic proline mutations on myosin assembly
J Mol Biol; Buvoli, M. et al; February 2012

Insights into Human b-cardiac Function from Single Molecule and Single Cell Studies
J. of Cardiovasc. Trans. Res.; Sivaramakrishnan, S. et al; July 2009

A FRET-Based Sensor Reveals Large ATP Hydrolysis-Induced Conformational Changes and Three Distinct States of the Molecular Motor Myosin
Cell; Shih, W.M. et al; September 2000

The Neck Region of the Myosin Motor Domain Acts as a Lever Arm to Generate Movement
Proc. Natl. Acad. Sci. USA; Uyeda, T.Q.P. et al; April 1996 

Single Myosin Molecule Mechanics:  Piconewton Forces and Nanometre Steps
Nature; Finer, J.T. et al; March 1994

Myosin Subfragment-1 is Sufficient to Move Actin Filaments In Vitro
Nature; Toyoshima, Y.Y. et al; August 1987

Fluorescent Actin Filaments Move on Myosin Fixed to a Glass Surface
Proc. Natl. Acad. Sci; Kron, J. et al; May 1986

Movement of Myosin-Coated Beads on Oriented Filaments Reconstituted from Purified Actin
Nature; Spudich, J.A. et al; June 1985