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Modulating fast skeletal muscle contraction protects skeletal muscle in animal models of Duchenne muscular dystrophy.
Russell AJ, DuVall M, Barthel B, Qian Y, Peter AK, Newell-Stamper BL, Hunt K, Lehman S, Madden M, Schlachter S, Robertson B, Van Deusen A, Rodriguez HM, Vera C, Su Y, Claflin DR, Brooks SV, Nghiem P, Rutledge A, Juehne TI, Yu J, Barton ER, Luo YE, Patsalos A, Nagy L, Sweeney HL, Leinwand LA, Koch K. Russell AJ, et al. Among authors: leinwand la. J Clin Invest. 2023 May 15;133(10):e153837. doi: 10.1172/JCI153837. J Clin Invest. 2023. PMID: 36995778 Free PMC article.
Surprisingly, even modest decreases of contraction (<15%) were sufficient to protect skeletal muscles in dystrophic mdx mice from stress injury. Longer-term treatment also decreased muscle fibrosis in key disease-implicated tissues. ...
Surprisingly, even modest decreases of contraction (<15%) were sufficient to protect skeletal muscles in dystrophic mdx mice from stress …
Regression of cardiac hypertrophy in health and disease: mechanisms and therapeutic potential.
Martin TG, Juarros MA, Leinwand LA. Martin TG, et al. Among authors: leinwand la. Nat Rev Cardiol. 2023 May;20(5):347-363. doi: 10.1038/s41569-022-00806-6. Epub 2023 Jan 4. Nat Rev Cardiol. 2023. PMID: 36596855 Free PMC article. Review.
The regression of pathological hypertrophy is associated with improved cardiac function, quality of life and long-term health outcomes. However, less than 50% of patients respond favourably to most therapies, and the reversibility of remodelling is influenced by many facto …
The regression of pathological hypertrophy is associated with improved cardiac function, quality of life and long-term health outcome …
Associations Between Female Sex, Sarcomere Variants, and Clinical Outcomes in Hypertrophic Cardiomyopathy.
Lakdawala NK, Olivotto I, Day SM, Han L, Ashley EA, Michels M, Ingles J, Semsarian C, Jacoby D, Jefferies JL, Colan SD, Pereira AC, Rossano JW, Wittekind S, Ware JS, Saberi S, Helms AS, Cirino AL, Leinwand LA, Seidman CE, Ho CY. Lakdawala NK, et al. Among authors: leinwand la. Circ Genom Precis Med. 2021 Feb;14(1):e003062. doi: 10.1161/CIRCGEN.120.003062. Epub 2020 Dec 7. Circ Genom Precis Med. 2021. PMID: 33284039
Regardless of genotype, women were at higher risk of mortality and developing severe heart failure symptoms. This points to a sex-effect on long-term myocardial performance in HCM, which should be investigated further....
Regardless of genotype, women were at higher risk of mortality and developing severe heart failure symptoms. This points to a sex-effect on …
Molecular Mechanisms Underlying Cardiac Adaptation to Exercise.
Vega RB, Konhilas JP, Kelly DP, Leinwand LA. Vega RB, et al. Among authors: leinwand la. Cell Metab. 2017 May 2;25(5):1012-1026. doi: 10.1016/j.cmet.2017.04.025. Cell Metab. 2017. PMID: 28467921 Free PMC article. Review.
Exercise elicits coordinated multi-organ responses including skeletal muscle, vasculature, heart, and lung. In the short term, the output of the heart increases to meet the demand of strenuous exercise. Long-term exercise instigates remodeling of the heart including …
Exercise elicits coordinated multi-organ responses including skeletal muscle, vasculature, heart, and lung. In the short term, the ou …
Estrogens mediate cardiac hypertrophy in a stimulus-dependent manner.
Haines CD, Harvey PA, Leinwand LA. Haines CD, et al. Among authors: leinwand la. Endocrinology. 2012 Sep;153(9):4480-90. doi: 10.1210/en.2012-1353. Epub 2012 Jul 3. Endocrinology. 2012. PMID: 22759381 Free PMC article.
These findings provide insight into the apparent loss of cardioprotection after menopause and suggest that caution is warranted in the long-term use of aromatase inhibitors in the setting of breast cancer prevention....
These findings provide insight into the apparent loss of cardioprotection after menopause and suggest that caution is warranted in the long- …
Intrathecal injection of naked plasmid DNA provides long-term expression of secreted proteins.
Hughes TS, Langer SJ, Johnson KW, Chavez RA, Watkins LR, Milligan ED, Leinwand LA. Hughes TS, et al. Among authors: leinwand la. Mol Ther. 2009 Jan;17(1):88-94. doi: 10.1038/mt.2008.230. Epub 2008 Oct 21. Mol Ther. 2009. PMID: 18941439 Free PMC article.
Here we demonstrate that i.t. injection of naked DNA can result in long-term expression of secreted proteins. Plasmids expressing either secreted alkaline phosphatase (SEAP) or human interleukin-10 (hIL-10) were injected into the i.t. space in rats, and transgene products …
Here we demonstrate that i.t. injection of naked DNA can result in long-term expression of secreted proteins. Plasmids expressing eit …
Intrathecal polymer-based interleukin-10 gene delivery for neuropathic pain.
Milligan ED, Soderquist RG, Malone SM, Mahoney JH, Hughes TS, Langer SJ, Sloane EM, Maier SF, Leinwand LA, Watkins LR, Mahoney MJ. Milligan ED, et al. Among authors: leinwand la. Neuron Glia Biol. 2006 Nov;2(4):293-308. doi: 10.1017/S1740925X07000488. Neuron Glia Biol. 2006. PMID: 18079973 Free PMC article.
Given that IL-1 is a key mediator of neuropathic pain, developing a clinically viable means of long-term delivery of IL-10 to the spinal cord is desirable. High doses of intrathecal IL-10-gene therapy using naked plasmid DNA (free pDNA-IL-10) is effective, but the dose req …
Given that IL-1 is a key mediator of neuropathic pain, developing a clinically viable means of long-term delivery of IL-10 to the spi …
Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy.
Freeman K, Lerman I, Kranias EG, Bohlmeyer T, Bristow MR, Lefkowitz RJ, Iaccarino G, Koch WJ, Leinwand LA. Freeman K, et al. Among authors: leinwand la. J Clin Invest. 2001 Apr;107(8):967-74. doi: 10.1172/JCI12083. J Clin Invest. 2001. PMID: 11306600 Free PMC article.
The medical treatment of chronic heart failure has undergone a dramatic transition in the past decade. Short-term approaches for altering hemodynamics have given way to long-term, reparative strategies, including beta-adrenergic receptor (betaAR) blockade. ...
The medical treatment of chronic heart failure has undergone a dramatic transition in the past decade. Short-term approaches for alte …