Breaking News
October 24, 2018 - Loxo Oncology Announces Receipt of Breakthrough Therapy Designation from U.S. Food and Drug Administration for LOXO-292 for the Treatment of RET Fusion-Positive Thyroid Cancer
October 24, 2018 - Analysis of largest set of genomes from pregnant women reveals genetic links to disease, birth outcomes
October 24, 2018 - New vaccine strategy shows promise to protect chickens against serious respiratory disease
October 24, 2018 - First Asia Reference Center in Singapore
October 24, 2018 - New partnership aims to tackle cancer health disparities
October 24, 2018 - Two Roche Diagnostic tests identified as transformative
October 24, 2018 - Cocaine overdoses on the rise with fentanyl combo flooding the market
October 24, 2018 - Radiotherapy combined with androgen-deprivation therapy improves overall survival up to 10 years
October 24, 2018 - Spectrum Pharmaceuticals Receives FDA Approval of Khapzory (levoleucovorin) for Injection
October 24, 2018 - Researcher uses smartphone to detect breast cancer gene
October 24, 2018 - Advanced breast cancer patients can benefit from immunotherapy-chemotherapy combination
October 24, 2018 - Stress related to social stigma negatively impacts mental health of autistic people
October 24, 2018 - New 17-item questionnaire may help detect GI disorders in children with autism
October 24, 2018 - 12% of frequent marijuana smokers experience cannabis withdrawal syndrome
October 24, 2018 - Immune therapy may be potential treatment option for patients with hard-to-treat ankylosing spondylitis
October 24, 2018 - Poor Experience With PCP Linked to Hospitalization in CKD
October 23, 2018 - Dummies not to blame for common speech disorder in kids
October 23, 2018 - The future of ethics and biomedicine: An interview
October 23, 2018 - X4 Pharmaceuticals announces clinical data of X4P-001-IO and Opdivo in patients with clear cell renal cell carcinoma
October 23, 2018 - FDA targets 465 websites that sell potentially dangerous, unapproved drugs
October 23, 2018 - New approach may lead to better diagnostic techniques for autoimmune disorders
October 23, 2018 - Innovative computer software sheds new light on genetic processes underlying deadly diseases
October 23, 2018 - Juul Drawing Lots of Teen Followers on Twitter
October 23, 2018 - WHO says Zika risk low in Pacific ahead of Meghan visit
October 23, 2018 - A deeper look at ‘Reflecting Frankenstein’
October 23, 2018 - Breastfeeding can have protective affect against high blood pressure in women, confirms study
October 23, 2018 - Epigenetic modifications may contribute to Alzheimer’s Disease
October 23, 2018 - Volunteering for peer counseling programs benefits people with lupus
October 23, 2018 - Cancer treatment may undergo a paradigm shift to immunotherapy soon
October 23, 2018 - Study uncovers new mechanism of action in a first-line drug for diabetes
October 23, 2018 - New type of molecule shows early promise against treatment-resistant prostate cancer
October 23, 2018 - Lancet publishes pioneering study of Aimovig’s efficacy in episodic migraine patients
October 23, 2018 - Scientists grow functioning human neural networks in 3D from stem cells
October 23, 2018 - Using mushrooms as a prebiotic may help improve glucose regulation
October 23, 2018 - New ENT clinic treats children in Zimbabwe
October 23, 2018 - CUIMC Celebrates 2018-2019, Issue 2
October 23, 2018 - Immunotherapy is better than chemotherapy as first-line treatment for advanced head and neck cancer
October 23, 2018 - Intake of painkillers during pregnancy linked to early puberty in future offspring
October 23, 2018 - ConnectToBrain project seeks to improve techniques for brain stimulation in current clinical use
October 23, 2018 - Polyganics begins first-in-human clinical trial of LIQOSEAL for reducing CSF leakage
October 23, 2018 - Gut bacterial community of healthy adults recovers after short-term exposure to broad-spectrum antibiotics
October 23, 2018 - Lowering systolic blood pressure does not damage the kidneys, shows study
October 23, 2018 - Incyte Announces Positive Data from Phase 2b Trial of Ruxolitinib Cream in Patients with Atopic Dermatitis
October 23, 2018 - Cardiovascular admissions more common among most deprived
October 23, 2018 - Targeted drug and hormone therapy combination extends breast cancer survival
October 23, 2018 - Map of human liver cells reveals molecular make-up of individual cells
October 23, 2018 - Drugs approved for breast cancer treatment are effective and well tolerated in men
October 23, 2018 - EKF introduces new hand-held lactate analyzer for rapid sports performance monitoring
October 23, 2018 - Researchers identify common genetic connection in lung conditions
October 23, 2018 - Forbius initiates Phase 2a trial evaluating efficacy, safety of AVID100 in patients with squamous NSCLC
October 23, 2018 - Immunotherapy achieves major pathological response in early-stage mismatch repair deficient colon cancer
October 23, 2018 - New discovery may lead to better treatment options for pancreatic cancer patients
October 23, 2018 - FDA Approves Dupixent (dupilumab) for Moderate-to-Severe Asthma
October 23, 2018 - Researchers identify immune culprits linked to inflammation and bone loss in gum disease
October 23, 2018 - Despite lower risk factors, black men have higher rates of recidivism
October 23, 2018 - Study finds why pregnant women in mainland China, Hong Kong and Taiwan prefer cesarean delivery
October 23, 2018 - AbbVie’s U-ACHIEVE Phase 2b/3 dose-ranging study improves outcomes in patients with ulcerative colitis
October 23, 2018 - NCI grant awarded to Abramson Cancer Center to study CAR T cells In solid tumors
October 23, 2018 - Scientists use electron microscope to study chemical transformation in catalytic cross-coupling reaction
October 23, 2018 - Research offers new hope to men who received childhood cancer treatment
October 23, 2018 - New medical navigation system receives international innovation award
October 23, 2018 - Adverse Childhood Experiences Tied to Burnout in BSN Students
October 23, 2018 - High levels of oral disease among elite athletes affecting performance
October 23, 2018 - Study examines effect of immediate vs delayed pushing during labor on delivery outcomes
October 23, 2018 - LU-RRTC to spearhead capacity-building efforts for racial and ethnic populations
October 23, 2018 - Maintenance therapy with olaparib improves progression-free survival in advanced ovarian cancer patients
October 23, 2018 - Organic food may protect against cancers finds study
October 23, 2018 - Interweaving anxiety disorder associated with stuttering remains unrecognized
October 23, 2018 - Cannabis oil shown to significantly improve Crohn’s disease symptoms
October 23, 2018 - Knowledge of sex differences in lower urinary tract may help stimulate breakthroughs in diagnosis, management
October 23, 2018 - Common antibodies associated with myocardial infarction
October 23, 2018 - Study reveals new treatment option for women with advanced breast cancer resistant to hormone therapy
October 23, 2018 - Brain’s ‘Self-Control’ Center May Be Key to Weight-Loss Success
October 23, 2018 - Prosthetic valve mismatches common in transcatheter valve replacement, ups risk of death
October 23, 2018 - Can virtual reality help people become more compassionate?
October 23, 2018 - Screen time eclipsed outdoor time for most students, shows study
October 23, 2018 - SLU researcher seeks to find solutions for ‘chemo brain’ symptoms and side effects of opioids
October 23, 2018 - Plastics now commonly found in human stools
October 23, 2018 - Zoledronic acid increases disease-free survival in premenopausal women with HR+ early breast cancer
October 23, 2018 - Cancer survivors at risk for heart failure during, after pregnancy
Penn research team identifies novel therapeutic target for heart disease

Penn research team identifies novel therapeutic target for heart disease

image_pdfDownload PDFimage_print

Changes in cellular struts called microtubules (MT) can affect the stiffness of diseased human heart muscle cells, and reversing these modifications can lessen the stiffness and improve the beating strength of these cells isolated from transplant patients with heart failure, found researchers from the Perelman School of Medicine at the University of Pennsylvania. This Nature Medicine new study is a continuation of research conducted two years ago on how MTs are involved in regulating the heartbeat. “These findings provide compelling evidence from human samples for a new therapeutic target for heart disease,” said senior author Ben Prosser, PhD, an assistant professor of Physiology. The Penn investigators aim to develop therapies that seek out the damaged MTs to reverse their harmful influence.

By suppressing impaired MTs, the team improved heart muscle cell function in damaged human cells. Normally, MTs of the cell’s inner support system have diverse structural and signaling roles. Alterations in this network have been suggested to contribute to heart disease. Recent studies suggest that chemical changes to the MTs, called detyrosination (the removal of a tyrosine chemical group), control the mechanics of heart beats. Detyrosinated MTs provide resistance that can impede the motion of contracting heart muscle cells.

The Penn team used mass spectrometry and mechanical tests of single heart muscle cells to characterize changes to the MT network and its consequences for normal heart function. Analysis of tissue from the left ventricle of heart transplant patients revealed a consistent upregulation of proteins that leads to the stiffening of MTs. Using super-resolution imaging, the team also saw a dense, heavily detyrosinated MT network in the diseased heart muscle cells, which is consistent with increased cell stiffness and decreased ability to contract. Proper cell elasticity and contraction is crucial for normal circulation throughout the body.

Using a drug, the team suppressed the detyrosinated MTs, which restored about half of lost contractile function in the diseased cells. Genetically reducing the MT detyrosination also softened the diseased cells and improved their ability to contract.

Past clinical data from Penn showed a direct correlation between excess MT detyrosination and a decline in heart function among patients with hypertrophic cardiomyopathy, a condition in which thickened heart muscle can cause problems in maintaining proper blood pressure levels and flow of blood through the heart.

The team found that detyrosination was greater in diseased hearts by comparing human heart tissue donated from heart transplant patients to normal heart tissue from other donors, obtained from work with transplant cardiologist and coauthor Ken Margulies, MD, a professor of Cardiovascular Medicine. Cells from diseased hearts have more MTs, and these MTs have more detyrosination. This process correlated with impaired function within this patient population in that their whole hearts, before the transplant, had a lower ejection fraction that correlated with greater detyrosination. Ejection fraction, an indicator of heart health, measures the amount of blood pumped out of ventricles with each contraction.

The team is now working on ways to target only heart muscle cell MTs. They are refining gene therapy approaches with the Penn Gene Vector Core to deliver an enzyme to the heart that reverses detyrosination in heart muscle cells.

Source:

https://www.pennmedicine.org/news/news-releases/2018/june/new-target-for-treating-heart-failure-identified-by-penn-medicine-researchers

Tagged with:

About author

Related Articles