La terapia, denominada deramiocel, es el primer tratamiento que ha demostrado preservar la función del corazón en la distrofia muscular de Duchenne, una enfermedad hereditaria poco frecuente que debilita progresivamente los músculos de todo el cuerpo. La insuficiencia cardíaca causada por esta enfermedad es una de las principales causas de muerte prematura.

“Después de más de dos décadas de trabajo, hemos demostrado que deramiocel puede ralentizar o incluso detener no solo la pérdida de la función de las extremidades superiores, sino también la progresión de la insuficiencia cardíaca en niños y jóvenes con Duchenne”, afirmó Eduardo Marbán, MD, PhD, director ejecutivo del Smidt Heart Institute de Cedars-Sinai y autor principal del estudio. Deramiocel se basa en los descubrimientos realizados por Marbán.

La distrofia muscular de Duchenne afecta principalmente a los niños porque es causada por una mutación en el cromosoma X. Los niños que nacen con esta mutación desarrollan debilidad muscular progresiva en todo el cuerpo, incluido el corazón. Con el tiempo, presentan dificultades para correr, saltar, andar en bicicleta y realizar otras actividades cotidianas, hasta perder la capacidad de caminar. Actualmente no existe una cura.

Resultados Positivos

El estudio aleatorizado y doble ciego, denominado HOPE-3, comparó deramiocel con un placebo en 106 participantes, de entre 10 y 22 años, con enfermedad avanzada. Cada tres meses, durante un año, los participantes recibieron una infusión intravenosa de deramiocel o placebo.

Los resultados mostraron que la terapia redujo en 54% el deterioro de la musculatura esquelética y ralentizó en 91% la progresión de la disfunción cardíaca. En los pacientes diagnosticados con miocardiopatía, una afección que reduce la capacidad del corazón para bombear sangre, quienes recibieron deramiocel mantuvieron completamente la función cardíaca o incluso mostraron una ligera mejoría.

“Los beneficios observados podrían traducirse en mejoras importantes en la calidad de vida de las personas con Duchenne avanzado”, señaló Craig McDonald, MD, profesor distinguido de Medicina Física y Rehabilitación y Pediatría en UC Davis Health e investigador principal nacional del estudio HOPE-3. “Si los jóvenes conservan la función de las extremidades superiores, podrán mantener actividades esenciales como alimentarse por sí mismos. Además, los beneficios para el corazón podrían reducir la mortalidad”.

Décadas de Investigación

Esta posible terapia adopta un enfoque diferente al de otros tratamientos estudiados para la distrofia muscular de Duchenne. Deramiocel se elabora a partir de células obtenidas de corazones sanos donados para trasplante que finalmente no pudieron utilizarse y que, de otro modo, habrían sido descartados.

La investigación comenzó en 2004, cuando Marbán aisló por primera vez una población de células progenitoras cardíacas conocidas como células derivadas de cardioesferas (cardiosphere-derived cells). Los primeros estudios clínicos con estas células se realizaron en Cedars-Sinai en pacientes que habían sobrevivido a un infarto.

Los resultados publicados en 2012 demostraron que las infusiones celulares regeneraban el músculo cardíaco dañado tras un infarto. Desde entonces, el equipo de Marbán ha investigado el potencial terapéutico de estas células en otras enfermedades y ha realizado descubrimientos clave, entre ellos que las células derivadas de cardioesferas secretan vesículas con moléculas de ARN que ayudan a reparar los tejidos del organismo.

En 2011, Catherine Jayasuriya, madre de un niño con distrofia muscular de Duchenne y defensora de los pacientes, convenció a Marbán de ampliar sus investigaciones desde la reparación del corazón tras un infarto hacia el estudio de esta enfermedad genética. La recaudación de fondos liderada por Jayasuriya proporcionó el financiamiento inicial que permitió al laboratorio de Marbán poner en marcha las primeras investigaciones. Posteriormente, la empresa biotecnológica Capricor Therapeutics obtuvo la licencia de la tecnología desarrollada por Marbán y continuó el trabajo mediante ensayos clínicos para evaluar la seguridad y eficacia de deramiocel.

“Este es el primer ensayo clínico de fase III que demuestra que una terapia celular es eficaz para tratar una enfermedad genética o cualquier tipo de enfermedad cardíaca”, afirmó Marbán, quien ocupa la cátedra Mark S. Siegel Family Foundation Distinguished Professor.

Los investigadores tienen previsto continuar estudiando los efectos terapéuticos de deramiocel, incluido su posible uso para tratar otras enfermedades con importantes necesidades médicas no cubiertas.

“Estos resultados representan un avance importante para las terapias celulares, impulsado por la incansable labor científica del Dr. Marbán y su equipo”, afirmó Shlomo Melmed, MB, ChB, vicepresidente ejecutivo de Asuntos Académicos y decano de la Facultad de Medicina de Cedars-Sinai.

Autores: La lista completa de investigadores del estudio HOPE-3 puede consultarse en el apéndice suplementario del artículo.

Financiamiento: El ensayo HOPE-3 fue financiado por Capricor Therapeutics Inc.

Divulgación de conflictos de interés: Eduardo Marbán, MD, PhD, es inventor de patentes licenciadas a Capricor Therapeutics Inc. y posee una participación accionaria como fundador de la compañía.

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The therapy, called deramiocel, is the first treatment shown to preserve heart function in Duchenne muscular dystrophy, a rare inherited disease that progressively weakens muscles throughout the body. Heart failure caused by Duchenne commonly leads to early death.

“After more than two decades of hard work, we have demonstrated that deramiocel can slow or even halt not only the loss of upper limb function, but also progression of heart failure in boys and young men with Duchenne,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai and senior author of the study. Deramiocel is based on Marbán’s discoveries.

Duchenne muscular dystrophy primarily affects boys because it is caused by a mutation on the X chromosome. Children born with this mutation develop muscle weakness throughout the body, including in the heart. As they grow older, these children have difficulty running, jumping, pedaling a bicycle and doing other activities, and eventually lose the ability to walk. There is no known cure.

Positive Findings

The randomized, double-blind study, called the HOPE-3 trial, compared deramiocel to placebo in 106 participants ages 10 to 22 with advanced disease. Every three months for one year, participants received an IV drip of either deramiocel or a placebo.

Results showed that the therapy slowed weakening of skeletal muscles by 54% and slowed heart dysfunction by 91%. In patients diagnosed with a condition called cardiomyopathy, which impedes the heart’s ability to pump blood, those who received deramiocel showed full preservation or slight improvement of heart function.

“The benefits we observed could mean important improvements in quality of life in people with advanced Duchenne,” said Craig McDonald, MD, distinguished professor of Physical Medicine & Rehabilitation and Pediatrics at UC Davis Health and national principal investigator of HOPE-3. “If young people maintain their upper limb function, it will help preserve their ability to do normal activities, such as feeding themselves. The heart benefits could reduce mortality.”

Decades in the Making

The potential therapy takes a different approach from other therapies that have been studied for Duchenne. Deramiocel is made from cells taken from healthy hearts donated for transplantation but unable to be used as such and that would otherwise be discarded. The work began in 2004, when Marbán first isolated a population of heart progenitor cells called cardiosphere-derived cells. The first clinical studies of cardiosphere-derived cells were performed at Cedars-Sinai, on patients who had survived heart attacks.

Results published in 2012 showed that the cell infusions regenerated heart muscle damaged by heart attack. Ever since, Marbán’s team has been studying the broader therapeutic potential of these cells. The investigators have made several important discoveries, such as that cardiosphere-derived cells secrete packets of RNA molecules that help cells repair the body’s tissues.

In 2011, Catherine Jayasuriya, the mother of a child with Duchenne and a patient advocate, influenced Marbán to turn his focus from studying how cardiosphere-derived cells could repair the heart after a heart attack to studying their potential for Duchenne muscular dystrophy. Jayasuriya’s fundraising provided the seed funding needed for Marbán’s laboratory to launch initial investigations. The biotechnology company Capricor Therapeutics licensed Marbán’s technology and continued the work by running clinical trials studying the safety and efficacy of deramiocel.

“This is the first Phase III trial to show that a cell therapy is effective against a genetic disease, or any type of heart disease,” said Marbán, the Mark S. Siegel Family Foundation Distinguished Professor. 

Investigators plan to continue studying the therapeutic effects of deramiocel, including whether it can be used to treat other diseases with major unmet medical needs.

“These results represent an important advance for cell-based therapy, one driven by relentless scientific pursuit made by Dr. Marbán and team,” said Shlomo Melmed, MB, ChB, executive vice president of Academic Affairs and dean of the Medical Faculty at Cedars-Sinai.

Authors: A complete list of HOPE-3 investigators can be found in the supplementary appendix of the study.

Funding: The HOPE-3 trial was funded by Capricor Therapeutics Inc.

Disclosures: Eduardo Marbán, MD, PhD, is an inventor of patents licensed by Capricor Therapeutics Inc. and holds founder's equity in the company.

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Led by interventional cardiologist Raj Makkar, MD, the six-and-a-half-year award from the Patient-Centered Outcomes Research Institute (PCORI) will fund a multi-center clinical trial of patients 50 and older who were born with a bicuspid aortic valve, a condition in which the aortic heart valve has two flaps regulating the flow of blood rather than the normal three. People with this condition typically develop aortic stenosis, when the aortic valve becomes so narrow that it impedes blood flow out of the heart.

Bicuspid aortic valve is the most common congenital heart condition, affecting approximately 2% of people, but little data exists comparing current treatments.

Heart valve disease can cause subtle symptoms at first but progress to heart failure if not diagnosed and treated early. Both surgery and transcatheter procedures are currently used to treat aortic stenosis. Transcatheter procedures use a thin, flexible tube called a catheter to reach the damaged valve. They are considered minimally invasive and are often recommended for patients who are at high risk for complications during surgery.

“Transcatheter aortic valve replacement has changed the paradigm for nonsurgical treatment of aortic stenosis, but it needs to be studied more rigorously in patients with bicuspid aortic valves,” said Makkar, a principal investigator of the study and vice president of Cardiovascular Innovation and Intervention at Cedars-Sinai. “We look forward to addressing this important evidence gap with this PCORI-funded randomized controlled trial in collaboration with our esteemed co-investigators.”

Patients with bicuspid aortic valve stenosis enrolled in the clinical trial will be randomly assigned to have their aortic valve replaced via open-heart surgery or by a transcatheter procedure. Investigators will review results from both groups to understand which option results in better health outcomes.  

The inaugural director of the Karsh Division of Interventional Cardiology, Makkar is an authority in minimally invasive approaches to treating heart valve disease.

“The Smidt Heart Institute at Cedars-Sinai is a leader in both heart surgery and minimally invasive heart procedures,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai and the Mark S. Siegel Family Foundation Distinguished Professor. “This study reflects our commitment to advancing heart research and care.”

“This research is a prime example of how Cedars-Sinai fosters innovation and brings leading-edge and clinically effective research directly to patient care,” said Shlomo Melmed, MB, ChB, Cedars-Sinai's executive vice president of Medicine and Health Sciences and dean of the Medical Faculty. “The findings from this clinical trial will help doctors globally advise their patients born with a bicuspid aortic valve on the best and safest approach for treating their cardiac condition.”

The award has been approved pending completion of a business and programmatic review by PCORI and issuance of a formal award contract. PCORI is a non-profit organization with a mission to fund research designed to provide patients, their caregivers and clinicians with the evidence-based information needed to make better-informed health care decisions.

Read more on the Cedars-Sinai Newsroom: $35M Gift Creates Karsh Division of Interventional Cardiology

, whose research into sudden cardiac arrest has led to novel methods of predicting the usually fatal condition, has been promoted to vice dean and chief artificial intelligence health research officer at Cedars-Sinai.

Chugh was also honored recently with the Heart Rhythm Society’s 2025 Distinguished Scientist Award for clinical science. The award was presented April 26 during Heart Rhythm 2025 in San Diego. 

“This award recognizes Dr. Chugh’s dedication to understanding sudden cardiac arrest and preventing this deadly emergency,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai.

The Distinguished Scientist Award is given to an investigator who has made a lasting impact on patient care and the field of heart rhythm research. Chugh has dedicated his career to improving prediction and prevention of sudden cardiac arrest, a heart rhythm disorder that causes the heart to stop and often leads to instant death. He has published more than 275 scientific papers.

“I’m grateful to the Heart Rhythm Society for this recognition of our work and accept it on behalf of my colleagues and mentees at Cedars-Sinai,” said Chugh, the Pauline and Harold Price Chair in Cardiac Electrophysiology Research. “Our team is motivated to make a real impact on this deadly condition.”

According to the American Heart Association, more than 356,000 out-of-hospital cardiac arrests occur each year in the U.S. Nearly 90% of them are fatal.

Chugh’s team discovered a new method for identifying the best candidates for the implantable defibrillator, a lifesaving intervention. They also combined data from emergency responders, medical records and biological samples to predict imminent sudden cardiac arrest within hours to days of warning symptoms. Their work has improved identification of people at risk and led to the term “near-term prevention” of sudden cardiac arrest.

Chugh is also a leader in artificial intelligence research, which he has harnessed to improve prediction of sudden cardiac arrest.

In his new role as vice dean and chief artificial intelligence health research officer, Chugh will oversee the translation of AI research into clinical trials and patient care. He will lead the new Artificial Intelligence in Medicine Research Center (AIMRC), which will help departments and institutes incorporate AI into their research.

“Dr. Chugh is a foremost investigator in both heart rhythm and AI research,” said Jeffrey Golden, MD, executive vice dean for Research and Education at Cedars-Sinai. “His use of AI to assess the risk for sudden cardiac arrest has the potential to advance the field and save lives. We are eager for him to broaden his AI research experience to all areas of clinical care at Cedars-Sinai.”

In 2024, Chugh received the Distinguished Scientist Award for clinical science from the American College of Cardiology. He is a member of the American Society for Clinical Investigation and the Association of American Physicians, and is past president of the Association of University Cardiologists and the Cardiac Electrophysiology Society.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Children with Duchenne typically lose the ability to walk by age 12 and die at a young age, commonly because their heart becomes so weak it can no longer pump blood.

“When we discovered he had Duchenne muscular dystrophy, I really felt like the sky had fallen down. I mean, that was my world,” Jayasuriya said from her home in Newport Beach, California, where she lives with her husband and Dusty.

Duchenne is caused by a mutation on the X chromosome and mostly affects boys. Jayasuriya was determined to find a potential treatment for her son and the approximately 20,000 other children diagnosed with Duchenne around the world each year.

Jayasuriya read a 2011 article in The Economist that described how Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai, was studying how heart stem cells might repair heart damage. A light bulb went off. She requested a meeting with Marbán and the two forged a mission-filled friendship.

In 2013 Jayasuriya raised $150,000 through her organization, Coalition Duchenne, to fund preliminary research. Now 32, Dusty stands to potentially benefit from a cell therapy created from research Marbán has pursued for decades and that his mother helped fund.

The U.S. Food and Drug Administration (FDA) is currently evaluating deramiocel, a cell product that is based on Marbán’s discoveries. If approved, deramiocel would be the first treatment for the heart damage that often kills young people with Duchenne muscular dystrophy.

Children with Duchenne first show problems with walking or moving their arms. Their heart deterioration isn’t obvious until the heart is close to failing.

“The heart is turning into leather inside their chest,” Marbán said. “They're not aware of it until they're much older because the heart has some reserve, but it ends up being heart failure that accounts for most of the deaths from Duchenne.”

Marban is scheduled to discuss his work at a Feb. 25 FDA virtual workshop on cell therapies. The workshop is open to the public and attendees must register here. Marban's presentation is part of a four-scientist panel, “Cell Therapies for Niche Indications: Clinical Insights and Future Directions.”

The Research Begins 

More than 20 years ago, Marbán became interested in using pluripotent stem cells, which can turn into almost any cell in the body, to reprogram heart cells to generate an electrical pulse in people with abnormal heart rhythms—a biological pacemaker. However, given their propensity to migrate and create tumors, such stem cells were not realistically ready for clinical testing. Marbán and colleagues then turned their attention to isolating from the adult human heart a special type of cell capable of repairing damaged tissue.

“The dogma at the time was that once the heart is injured, it's permanent and it doesn't recover,” Marbán said.

In his laboratory, then at Johns Hopkins University, Marbán developed a technique, starting with a small human heart biopsy, to enable heart cells to self-assemble into microscopic clusters called cardiospheres. He and his team further cultured cardiospheres so that they would dissociate into cardiosphere-derived cells or CDCs. The CDCs could be grown in a laboratory and given back to the patient from whose heart they were taken.

When Marbán joined Cedars-Sinai in 2007 as the inaugural director of the Smidt Heart Institute, he began translating his basic work on CDCs into therapeutic studies in patients. Clinical trials showed heart attack patients who received infusions of their own CDCs into their hearts had some regrowth of healthy heart muscle. Curiously, additional research revealed it wasn’t the cells themselves that did the repair.

Ahmed Ibrahim, PhD, MPH, once a PhD student in Marbán’s lab who is now assistant professor of Cardiology at Cedars-Sinai, discovered that CDCs secrete tiny fat droplets called exosomes. These exosomes are full of molecules that support heart repair. This revelation meant that rather than biopsy a patient's heart, grow the cells and inject those cells into the same patient a month later, investigators could use donor hearts to prepare thousands of doses of CDCs that could be available “off the shelf.” Donor hearts are typically donated for transplantation but may be used for research if they cannot be used for a suitable recipient for technical reasons.

Duchenne and Heart Disease

Jayasuriya piqued Marbán’s interest in Duchenne heart disease. He began to study the effects of CDCs in laboratory mice with a genetic defect mirroring that in Duchenne patients. Working with Marbán, Smidt Heart Institute Assistant Professor Russell Rogers, PhD, discovered that CDCs worked well in Duchenne mice when given intravenously, leading to clinical trials in patients with Duchenne. The research verified CDCs could improve heart and muscle function in boys and young men with Duchenne.

The biotechnology company Capricor Therapeutics licensed Marbán’s technology and conducted additional clinical trials that led the company to apply for FDA approval of CDCs, now known as deramiocel, in December 2024. If deramiocel is approved, patients with Duchenne could receive an intravenous infusion of the therapy every three months.

“Our hope is that this therapy will meaningfully slow the progression of the disease and extend patient lives,” Marbán said.

Investigators in Marbán’s laboratory group are continuing to study what makes exosomes from CDCs potent.

“CDCs work by secreting tiny vesicles packed with genetic material,” Rogers said. “We are looking into the possibility that some of this genetic material may be effective when delivered on its own.”

For Dusty, who has lived longer than most people with Duchenne, the potential therapy is a chance to save his heart.   

“This is great news for older people with Duchenne like me,” he said. “This could make a true difference and impact on my life.”

Jayasuriya said the approval would be a game changer. She encourages parents of children with a rare disease like Duchenne not to give up hope.

“There may be something that works for another condition that can actually work for the condition your child has,” she said. “You just never know. There are no rules.”

Read more on the Cedars-Sinai Newsroom: Cell-Derived Therapy May Help Repair Abnormal Heart Rhythm

Heart failure occurs when the heart cannot pump enough blood and oxygen to support the body’s other organs. This condition can cause fatigue, shortness of breath, swelling, other debilitating symptoms and shorten life. Heart attacks, which damage the heart muscle, are among the most common causes.

The new study, published in European Heart Journal, analyzed the effect of administering a small molecule known as PR-364 to adult male laboratory mice that endured a heart attack, also known as myocardial infarction. Data showed this treatment preserved the heart’s pumping power and mitigated the progression of heart failure in the treated mice versus mice that were not treated.

To uncover why PR-364 had such a profound impact, the investigators performed additional laboratory experiments using mouse tissue and cells along with human cardiomyocytes, the cells that make up the heart muscle. They also analyzed changes in proteins in mice that had received the drug.

The data indicated that PR-364 enhanced the functioning of mitochondria, the small structures in cells that generate energy to power biochemical reactions. Healthy mitochondria are critical drivers of the processes that protect and repair the heart and other muscles. PR-364 altered the mitochondria in several beneficial ways:

• By increasing mitophagy, the process by which the mitochondria that have been damaged by a heart attack are destroyed and cleared from the body, which aids repair of the heart muscle
• By increasing production of new mitochondria
• By improving the overall functioning of the mitochondria

“Taken together, these effects suggest how PR-364 helped prevent the development of heart failure after heart attacks in laboratory mice,” said Jennifer Van Eyk, PhD, professor of Cardiology in the Smidt Heart Institute at Cedars-Sinai and director of the Advanced Clinical Biosystems Institute at Cedars-Sinai. “While our data does not prove that PR-364 would have this impact on patients, it points to a unique, promising path toward developing heart failure strategies for survivors of heart attacks.” Van Eyk was co-corresponding author of the study along with Roberta Gottlieb, MD, formerly of Cedars-Sinai.

Van Eyk said the next steps in this research are threefold: to study whether a second-generation version of PR-364 may be more effective, to determine whether there are differences in responses based on gender and to delve more deeply into how PR-364 works.

Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai, said the new study’s findings are especially important, given that more people than ever are surviving heart attacks.

“Although several drugs have reduced injury in mice after a heart attack, almost all are preventive: They must be given beforehand. Unfortunately, no one has a crystal ball predicting just when a heart attack will occur in real life,” Marbán said. “What is particularly noteworthy here is the fact that improved recovery was seen when PR-364 was administered a full two hours after the heart attack, improving the likelihood of successful translation to patients.”

Other Cedars-Sinai authors include co-first authors Lizhuo Ai and Juliana de Freitas Germano, and Chengqun Huang, Marianne Aniag, Savannah Sawaged, Jon Sin, Reetu Thakur, Deepika Rai, Yang Song, Honit Piplani, Robert M. Mentzer and Aleksandr Stotland. Other authors include Christopher Rainville, David E. Sterner, Suresh Kumar and Tauseef R. Butt.

Disclosure of interest: The authors declare no conflicts of interest. The Parkin activating compound PR-364 was provided by Progenra Inc., which did not interfere with the results and conclusions presented here. Progenra Inc. plans to file patents on PR-364.

Funding: This work was supported by the National Institutes of Health (NIH) grants R01-HL144509 (J.E.V.E. and R.A.G.), R01-HL132075-01A (J.E.V.E. and R.A.G.), 1 R01 HL155346-01 (E.M. and J.E.V.E.), and1R43HL162163-01 (Progenra, Inc.). L.A. is supported by the California Institute for Regenerative Medicine (CIRM) Scholar Training Program (CIRM EDUC4-12751). A.S. is supported by the Cedars-Sinai Research Institute Winnick award AWD00001135-400023. Progenra’s work was supported by Michael J Fox Foundation, New York, USA. As well, the Erika J Glazer Endowed Chair in Women’s Heart Health (J.E.V.E.) and the Smidt Heart Institute and Cedars-Sinai Medical Center funds to J.E.V.E. for proteomic analysis.

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, hosted by Cedars-Sinai on Oct. 25.

“This meeting isn’t just for scientists,” said Michael I. Lewis, MD, program director of The Alpha Clinic at Cedars-Sinai and professor of Medicine. “It is for clinicians, patients and members of the public who are interested in learning more about cell and gene therapies, emerging technologies, innovative clinical trial designs and issues surrounding accessibility to these therapies for patients, such as financial barriers.”  

The symposium, sponsored by the California Institute for Regenerative Medicine (CIRM), will take place from 9 a.m.-5 p.m. at the Cedars-Sinai Silver Screen Theater in the Pacific Design Center. Virtual registration is also available.

Scientists from all nine California Alpha Clinics are set to speak. Along with Cedars-Sinai, institutions with alpha clinics include University of California, San Diego; University of California, Los Angeles; University of Southern California and Children’s Hospital Los Angeles; Stanford University; University of California, Irvine; University of California, Davis; City of Hope; and University of California, San Francisco.

Directors of several Alpha Clinics will moderate panel discussions, and directors of the Alpha Clinics at UC Irvine, UC San Diego, University of Southern California and UC Davis will participate in a discussion of Alpha Clinic operations. Daniela A. Bota, MD, PhD, director of the UC Irvine Alpha Clinic, will talk about chimeric antigen receptor (CAR) therapies, and Mark Walters, MD, UC San Francisco Alpha Clinic director, will discuss current gene therapies, future opportunities and barriers to treatment. 

Lewis expects speakers to highlight the importance of diversity in clinical trials, promote collaboration among researchers and showcase advances in cell and gene therapies.

“The symposium will look to the current status of the field and, more importantly, to the future, as new approaches and therapies are likely to rapidly expand,” said Clive Svendsen, PhD, co-associate project director of Cedars-Sinai's Alpha Clinic and executive director of the Board of Governors Regenerative Medicine Institute at Cedars-Sinai. Svendsen recently co-authored a review paper published in Nature Medicine about stem cell-based therapies for neurological conditions.

The review paper describes stem cell-based treatments for a number of neurological disorders, including amyotrophic lateral sclerosis, also known as ALS. The condition affects nerve cells in the brain and spinal cord that control movement. ALS eventually causes loss of the ability to move, speak, eat and breathe. At this time there is no cure.

The Cedars-Sinai Alpha Clinic is conducting a trial of a therapy, developed by Svendsen and his team, using specially engineered cells to protect damaged motor neurons. To date, six patients have been treated, with no major complications.

Cedars-Sinai’s Alpha Clinic and others throughout California are developing stem-cell based therapies for a variety of conditions: 

• Cedars-Sinai is studying a therapy for retinitis pigmentosa, which breaks down cells in the light-sensitive layer at the back of the eye, the retina, leading to vision loss. The therapeutic cells in the trial release proteins that help protect retinal cells from damage.
• Cedars-Sinai investigators also are testing a treatment for pulmonary arterial hypertension, a rare condition in which elevated blood pressure in lung blood vessels can damage the heart. The initial study was led by Lewis, director of Respiratory Care Services at Cedars-Sinai, and Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute and associate project director of The Alpha Clinic. Investigators concluded that infusions of specialized cell products derived from heart tissue seemed to improve patients’ heart and lung health.
• Alpha Clinics throughout California are studying stem cell-based therapies for several other conditions—including movement disorders such as Parkinson’s disease and Huntington’s disease; Alzheimer’s disease; stroke; epilepsy; spinal cord injury; and multiple sclerosis.

“The Alpha Clinic network is dedicated to accelerating the work of institutions in California, such as Cedars-Sinai, that are developing and testing cell and gene therapies,” Marbán said. “It is a highly collaborative group, and we share resources including our expertise, our infrastructure and our experience with cell delivery to help each other.”

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The first 100 minimally invasive tricuspid procedures were done as part of the TRISCEND II clinical trial. The trial studied replacing a malfunctioning tricuspid valve with a bioprosthetic valve to treat patients with tricuspid regurgitation, a condition in which the heart’s tricuspid valve does not close tightly, causing blood to leak backward from the heart into the veins of the body.

The tricuspid valve has historically been the most challenging of the heart’s four valves to treat because of its location in the back of the heart.

“The Smidt Heart Institute is the only institution to have completed this many minimally invasive tricuspid valve replacement procedures, bringing extensive expertise and new options to patients impacted by tricuspid valve disease,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute and the Mark S. Siegel Family Foundation Distinguished Professor. “This impressive feat is a testament to our team’s skill in difficult-to-treat valvular conditions.”

Raj Makkar, MD, associate director of the Smidt Heart Institute and vice president of Cardiovascular Innovation and Intervention for Cedars-Sinai, was the principal investigator for the TRISCEND II trial at Cedars-Sinai.

During a minimally invasive tricuspid valve replacement procedure, an interventionalist threads a thin, flexible tube called a catheter through a vein to reach the tricuspid valve. Early results of the trial led to the FDA approving the Edwards EVOQUE Tricuspid Valve Replacement System to treat eligible patients with tricuspid regurgitation.

Makkar led the Smidt Heart Institute team that performed the first EVOQUE implantation following FDA approval and has the most extensive experience globally in this groundbreaking procedure.

“We are proud and humbled to be the first in the U.S. to have implanted the world’s first commercially available transcatheter tricuspid valve,” said Makkar, the Stephen R. Corday, MD, Chair in Interventional Cardiology. “It is moments like this that further our dedication, commitment and passion to the field of interventional cardiology.”

The heart has four valves (aortic, mitral, pulmonic, and tricuspid) that open and close to move blood through the heart and to the rest of the body. If a valve cannot open or close fully it can interfere with blood flow and cause a host of health issues, including heart attack and stroke.

Moderate and severe tricuspid disease is common in the U.S. and affects an estimated 1.6 million people. Some people can manage their valvular heart disease with medications, but others need to have the damaged valve repaired or replaced.

The tricuspid valve is typically replaced during open-heart surgery. In contrast, the catheter-based approach used at Cedars-Sinai involves a tiny incision and patients typically go home the same day.

"The transcatheter tricuspid valve replacement system is a game-changer for patients with tricuspid regurgitation, a condition that has traditionally been overlooked," said Christine M. Albert, MD, MPH, chair of the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai. “We are proud to be the center with the most experience in transcatheter tricuspid valve replacement, demonstrating our commitment to pioneering new treatments and expanding options for those impacted by tricuspid valve disease.”

Read more on the Cedars-Sinai Blog: Treatment Options for Heart Valve Disease

Es un corto camino, pero ha sido todo un recorrido para Sánchez, una “Dreamer” cuyo estatus migratorio está en el limbo pero cuyas aspiraciones no.

Los Dreamers son adultos jóvenes cuyos padres los trajeron a los EE. UU. cuando eran niños. El programa de Acción Diferida para los Llegados en la Infancia (DACA, por sus siglas en inglés) otorga a Sánchez y a otros autorización, como inmigrantes indocumentados, para trabajar legalmente en los EE. UU.

Pero el estatus migratorio no fue el único obstáculo para Sánchez.

“Siempre había querido trabajar en ciencias, pero nunca había conocido a nadie en investigación que se pareciera a mí o me diera una oportunidad”, dijo Sánchez, que era una niña pequeña cuando sus padres emigraron a Estados Unidos desde México.

Es decir, hasta 2015, cuando el Dr. Eugenio Cingolani, asistió a un evento de networking para estudiantes de la Universidad Estatal de California en Los Ángeles.

Cingolani, director de Investigación Preclínica y profesor asociado de Cardiología en el Smidt Heart Institute, conoció a Sánchez allí. Impresionado con su entusiasmo y determinación cuando dio un paso adelante para expresar su interés en una posible pasantía, Cingolani la invitó a visitar su recién establecido laboratorio. Unas semanas más tarde, Sánchez era becaria desde las 7 p.m. hasta la medianoche, después de que terminaran sus clases y entre tres trabajos para pagar la matrícula. Le encantó la pasantía, ya que le brindó la oportunidad de aprender sobre los marcapasos biológicos, un área de investigación en la que sobresale el Smidt Heart Institute.

Pronto, Sánchez tuvo un trabajo de tiempo completo en el laboratorio de Cingolani.

“Liz tiene valor, convicción y perseverancia, todo esto seguirá dando sus frutos a lo largo de su vida”, comentó el Dr. Eduardo Marbán, PhD, director ejecutivo del Smidt Heart Institute. “Está en camino hacia la carrera que siempre quiso y ya ha realizado valiosas contribuciones al trabajo del Smidt Heart Institute”.

De hecho, Sánchez es la primer autora de un estudio reciente publicado en la revista médica revisada por pares Cell Reports Medicine sobre cómo la tecnología de ARN puede crear actividad de marcapasos espontánea en el cuerpo, un proyecto que Marbán y Cingolani han denominado "marcapasos biológico".

Al recordar sus ocho años en Cedars-Sinai, Sánchez sigue agradecida.

"El Dr. Cingolani vio más allá de mi estatus migratorio”, dijo Sánchez. “Él vio mi potencial y mi amor por la investigación médica. Me dio una oportunidad”.

La Perseverancia Retribuye

Sánchez tenía 3 años cuando su familia huyó de la Ciudad de México y aterrizó en el área de Koreatown de Los Ángeles. En ese momento, el crimen era rampante y la violencia de las pandillas era común. Dormían en el suelo de un apartamento de una habitación que compartían con otras cuatro personas. Sánchez recuerda que su padre se iba todos los días a las 3 a. m. al trabajo.

Cuando tenía 8 años, el interés de Sánchez por la ciencia comenzó a florecer, gracias al reumatólogo de su madre.

“Su nombre era Dra. Christine Evelyn, y era mucho más que una médica que trató la artritis reumatoide de mi mamá”, dijo Sánchez. “Ella me trajo el campo de la medicina. Ella me decía: 'Deberías hacer algo en ciencias, eres muy inteligente y curiosa'. Me dio libros, nos dio ropa, grabó el abecedario para ayudarnos a aprender inglés. Ella trató a toda nuestra familia cuando estábamos enfermos, por muy poco dinero. Ella hizo mucho, mucho más de lo necesario, por nosotros”.

La reumatóloga se jubiló cuando Sánchez tenía 12 años, pero instó a la joven a “seguir trabajando duro, sacar buenas notas y no dejar la escuela. Puedes hacer lo que quieras hacer.”

Sánchez cumplió con los deseos de la doctora y espera volver a conectarse y agradecerle.

“No solo me gradué con un título en microbiología de Cal State Los Ángeles, sino que este verano buscaré un doctorado en medicina biomédica y traslacional aquí en Cedars-Sinai”.

Mover Barreras

Sánchez siempre sobresalió en la escuela. Tomó cursos avanzados en la escuela secundaria, realizó actividades extracurriculares y se graduó con honores. Pero cuando se trataba de la universidad, no ser ciudadano estadounidense fue un obstáculo. No podía obtener ayuda financiera y sus padres no podían pagar la matrícula en una universidad de cuatro años.

“Hice todo lo que tenía que hacer para financiar mi educación”, dijo Sánchez, que ahora tiene 34 años. “Tomé prestados libros de compañeros de clase, usé ediciones antiguas de libros renovados y pagué la matrícula como pude. Me llevó casi 10 años graduarme”.

Cuando se firmó DACA en 2012, al instante hubo más oportunidades disponibles.

“DACA representó para personas como yo que el cielo era el límite de lo que podíamos lograr”, dijo Sánchez. “Me permitió trabajar en Cedars-Sinai, que ha cambiado mi vida. Podría haber renunciado a la escuela si no fuera por DACA, y si no hubiera encontrado el laboratorio del Dr. Cingolani”.

Sánchez fue la primera en su familia en ir a la universidad. Sus orgullosos padres, que no asistieron a la escuela después del tercer grado, a menudo le recuerdan que a lo largo de su vida, cuando las puertas se han cerrado, siempre ha logrado abrir una ventana.

Orgullosa de Publicar

Poco después de que Sánchez se uniera al laboratorio de Cingolani, le encargó que investigara cómo usar la tecnología de ARN mensajero (que, años más tarde, se usó para crear las vacunas contra el COVID-19) para crear células que marcarían naturalmente la frecuencia cardíaca. El objetivo es que estos marcapasos biológicos reemplacen algún día a los marcapasos electrónicos tradicionales.

Sus hallazgos finalmente llevaron al estudio publicado, en el que Cingolani y Marbán son los autores correspondientes.

“Liz es una investigadora ejemplar, increíblemente inteligente, dedicada y talentosa”, dijo Cingolani. “También es una mentora extraordinaria que ayuda a quienes la rodean y pueden necesitar ayuda o palabras de aliento. Ella cree en ayudar a los demás porque en el camino fue ayudada por personas que le proporcionaron una base de partida. Liz personifica el futuro de la ciencia y la medicina, y estoy ansioso por ver a dónde la lleva su ya exitosa carrera”.

Marbán dijo: “La historia de Liz nos enseña muchas cosas, una de las cuales es el poder de las pequeñas buenas acciones para tener un gran impacto. Aquí, la buena acción fue la voluntad del Dr. Cingolani de presentar la carrera de medicina a un grupo de estudiantes de Cal State LA. Liz se inspiró y valientemente se acercó a él para una pasantía, y el resto es historia. Se cambió una vida. El mundo es un mejor lugar."

Sánchez continúa buscando nuevas ventanas por abrir y está ansiosa por ver a dónde conducen.

“Me encantaría tener mi propio laboratorio y convertirme en investigadora principal”, dijo. “Quiero brindarles a otros las mismas oportunidades que me brindaron el Dr. Cingolani y el Dr. Marbán, y fomentar el talento entre las personas, especialmente las mujeres, que se dedican al desarrollo de nuevas terapias o que quieren estar en la primera línea de la atención al paciente.

“Quiero que sepan que si realmente entregan su corazón a su pasión y dicen que sí a las oportunidades, la vida los compensará”.

It’s a short walk—yet it has been quite a journey for Sanchez, a so-called “Dreamer” whose immigration status is in limbo but whose aspirations are not.

Dreamers are young adults whose parents brought them to the U.S. as children. The Deferred Action for Childhood Arrivals (DACA) program gives Sanchez and others authorization, as undocumented immigrants, to legally work in the U.S.

But immigration status wasn’t Sanchez’s only hurdle.

“I had always wanted to work in science but had never met anyone in research who looked like me or gave me an opportunity,” said Sanchez, who was a toddler when her parents immigrated to the U.S. from Mexico.

That is, until 2015, when Eugenio Cingolani, MD, attended a California State University of Los Angeles networking event for students.

Cingolani, director of Preclinical Research and associate professor of Cardiology at the Smidt Heart Institute, met Sanchez there. Impressed with her enthusiasm and determination when she stepped up to express interest in a potential internship, Cingolani invited her to visit his newly established lab. A few weeks later, Sanchez was interning from 7 p.m. to midnight, after her classes ended and between the three jobs she was working to pay tuition. She loved the internship, as it afforded her the opportunity to learn about biological pacemakers—a research area in which the Smidt Heart Institute excels.

Soon, Sanchez had a full-time job in Cingolani’s lab.

“Liz has courage, conviction and perseverance, all of which will continue to pay off throughout her life,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute. “She is well on her way to the career she always wanted and has already made valuable contributions to the Smidt Heart Institute’s work.”

In fact, Sanchez is the first author of a recent study published in the peer-reviewed medical journal Cell Reports Medicine about how RNA technology can create spontaneous pacemaker activity in the body, a project Marbán and Cingolani have dubbed “biological pacemaker.”  

Thinking back over her eight years at Cedars-Sinai, Sanchez remains grateful.

“Dr. Cingolani saw beyond my immigration status,” Sanchez said. “He saw my potential and my love for medical research. He gave me a chance.”

Perseverance Pays

Sanchez was 3 years old when her family fled Mexico City and landed in the Koreatown area of L.A. At the time, crime was rampant and gang violence was common. They slept on the floor of a one-bedroom apartment they shared with four other people. Sanchez remembers her father leaving at 3 a.m. for work every day.

When she was 8, Sanchez’s interest in science began to blossom, thanks to her mother’s rheumatologist.

“Her name was Dr. Christine Evelyn, and she was much more than a physician who treated my mom’s rheumatoid arthritis,” Sanchez said. “She brought the field of medicine to me. She’d tell me, ‘You should do something in science—you’re very smart and curious.’ She gave me books, she gave us clothes, she recorded the ABCs to help us learn English. She treated our whole family when we were sick, for very little payment. She took many, many extra steps for us.”

The rheumatologist retired when Sanchez was 12, but she urged the young girl to “continue to work hard, get good grades and don’t leave school. You can do anything you want to do.”

Sanchez made good on the physician’s wishes for her and hopes to reconnect and say thank you.

“I not only graduated with a degree in microbiology from Cal State Los Angeles, this summer I’ll be pursuing a PhD in biomedical and translational medicine here at Cedars-Sinai.”

Moving Roadblocks

Sanchez always excelled in school. She took high school advanced placement classes, did extracurricular activities and graduated with honors. But when it came to college, not being an American citizen was a roadblock. She could not get financial aid, and her parents could not afford the tuition at a four-year university.

“I did whatever I needed to do to finance my education,” said Sanchez, now 34. “I borrowed books from classmates, I used old editions of refurbished books, and I paid tuition as I could. It took almost 10 years to graduate.”

When DACA was signed in 2012, more opportunities were instantly available.

“DACA represented to people like me that the sky was the limit on what we could achieve,” Sanchez said. “It allowed me to work at Cedars-Sinai, which has been life changing. I may have given up on school if not for DACA—and if I hadn’t found Dr. Cingolani’s lab.”

Sanchez was the first in her family to go to college. Her proud parents, who did not attend school past third grade, often remind her that throughout her life when doors have closed, she’s always managed to open a window.

Proud to Publish

Soon after Sanchez joined Cingolani’s lab, he tasked her with researching how to use messenger RNA technology (which, years later, was used to create the COVID-19 vaccines) to create cells that would naturally set the heart’s beating rate. The goal is for these biological pacemakers to one day replace traditional electronic pacemakers.

Her findings eventually led to the published study, on which Cingolani and Marbán are corresponding authors.

“Liz is an exemplary researcher—incredibly smart, dedicated, talented,” Cingolani said. “She is also an extraordinary mentor who helps those around her who may need an assist or words of encouragement. She believes in helping others because she was helped along the way by people who provided stepping stones for her. Liz epitomizes the future of science and medicine, and I’m eager to see where her already successful career leads her.”

Said Marbán, “Liz’s story teaches us many things, not least of which is the power of small good deeds to have an outsize impact. Here, the good deed was the willingness of Dr. Cingolani to pitch medicine as a career to a group of Cal State LA students. Liz was inspired and courageously approached him for an internship, and the rest is history. A life was changed. The world is a better place.”

Sanchez continues to look for new windows she can open and is eager to see where they lead.

“I’d love to have my own lab and become a principal investigator,” she said. “I want to give others the same opportunities that Dr. Cingolani and Dr. Marbán gave me, and to foster talent among people—especially women—who are devoted to developing new therapies or who want to be on the front lines of patient care.

“I want them to know that if they genuinely give their heart to their passion, and say yes to the opportunities, life will compensate them.”

Read more on the Cedars-Sinai Blog | Pacemakers: An Evolution