May 15, 2017 | Featured, Patient Stories, Research
‘‘The drug works. It gives you your life back,” says Austin Jacobson. Watch the video
The U.S. Food and Drug Administration has approved a new biologic drug that is based on seminal research by Emma Guttman-Yassky, MD, Professor of Dermatology, and Medicine (Clinical Immunology), at the Icahn School of Medicine at Mount Sinai. The drug, dupilumab, was approved in March—fast-tracked because it is a “breakthrough therapy” for adult patients with uncontrolled eczema. “It brings hope to patients who have tried everything.” Dr. Guttman-Yassky says.
One of them is her patient Austin Jacobson, a personal injury defense lawyer in Manhattan. “Living with eczema is like having poison ivy from head to toe,” he says. “You can’t sleep because you’re itching so badly. It affects every single aspect of your life.” Mr. Jacobson took part in clinical trials of the drug, which is injected every two weeks, and still uses it now. He says he felt relief from itching “two hours after taking the first injection.”
Emma Guttman-Yassky, MD, Professor of Dermatology, and Medicine (Clinical Immunology), at the Icahn School of Medicine at Mount Sinai
At least 31 million Americans are affected by some form of eczema. The most common type is atopic dermatitis, caused by a combination of genetic, immune and environmental factors. Dupilumab, sold by Regeneron Pharmaceuticals as Dupixent, is an antibody that binds to a protein, IL-4 receptor alfa, inhibiting the inflammatory response that leads to eczema’s rashes and itching. Dr. Guttman-Yassky’s laboratory was the first to map immune pathways underlying eczema, including those now targeted by dupilumab and other drugs in clinical trials.
Her team is among those testing more new therapies, including a drug made by Pfizer Inc. that targets a different immune molecule, interleukin 22 or IL-22. Dr. Guttman’s research was the first to identify the lymphocytes that produce IL-22, and show their link to eczema. With funding from the National Institutes of Health, she designed a study that tested IL-22 antibody targeting in the clinic and in the lab—a treatment that is showing promising preliminary results.
“These are exciting times for patients with eczema, and for me specifically, as I am able to contribute to the scientific development for this disease and help millions of patients worldwide,” Dr. Guttman-Yassky says. “This is a dream come through for a physician-scientist.”
As for Mr. Jacobson, he says that his skin, which had been “100 percent” covered with a scaly, flaking rash, is now largely clear. “The drug works,” he says of dupilumab. “It gives you your life back.”
Dr. Guttman-Yassky has received research funding from Regeneron, and drug and research support from Pfizer, and is working with most companies developing treatments for atopic dermatitis/eczema.
Updated on Jun 30, 2022 | Featured, Research
The CT scan, left, shows the 85 cc intracerebral hemorrhage. The CT scan, right, was performed on postoperative day 1 and shows complete evacuation of the hematoma.
Spontaneous bleeding in the brain, known as intracerebral hemorrhage (ICH), remains the least treatable and most devastating form of stroke. While it accounts for only 15 percent of all strokes, it is a leading cause of mortality, morbidity, and disability worldwide, and few effective treatment options exist. Over recent months, however, Mount Sinai physicians have taken a leading national role in creating and implementing a new minimally invasive technique that is showing promise.
ICH occurs when a small artery in the brain leaks blood directly into surrounding tissue and forms a localized hematoma (clot), which continues to destroy neurons and causes life-threatening pressure on the brain. Loss of balance, blurry vision, and difficulty speaking are among the common symptoms, as well as headache and vomiting, which increase gradually over minutes to hours.
This sequence demonstrates the steps of the endoscopic evacuation procedure including placement of the sheath into the hematoma (A), aspiration of the hematoma (B), irrigation ofthe cavity (C), and removal of the sheath (D).
The effort is being led by J Mocco, MD, MS, Director of the Cerebrovascular Center at the Mount Sinai Health System, and Professor and Vice Chair for Education in the Department of Neurosurgery at the Icahn School of Medicine at Mount Sinai, and Christopher Kellner, MD, Director of the Intracerebral Hemorrhage Program at Mount Sinai and Assistant Professor of Neurosurgery.
Over the course of 15 months, they have treated nearly 50 patients with a novel strategy to evacuate blood clots using ultrasound imaging, paired with intraoperative CT
scanning and MRI-guided navigation, to precisely locate the blood clot within the brain. Through a tiny hole in the skull, a sheath containing a camera and an experimental suction device, known as the Apollo™ System, is navigated to the clot. The physicians then aspirate the clot with the Apollo device, normalizing the brain pressure.
J Mocco, MD, MS, left, and Christopher Kellner, MD
In 2016, Dr. Mocco was named co-principal investigator of a Phase I clinical trial that will enroll approximately 50 patients at 10 sites across the United States to test the feasibility, safety, and efficacy of this procedure when compared to previously published standards. The trial, called the INVEST trial, is funded by Penumbra, Inc., the company that developed the Apollo System, and is scheduled to commence in May.
“We have just completed a six-month follow-up for the first 28 patients treated with this device, and although the data are preliminary, it appears that patients overall are doing very well with this procedure,” says Dr. Mocco.
One recent patient—an extremely active 86-year-old classical pianist—presented to Mount Sinai Beth Israel in February. “He came in with left arm and leg paralysis, slurred speech, and lethargy,” says Dr. Kellner. A CT scan revealed a very large 85 cc hemorrhage, and he was transferred to the Intracerebral Hemorrhage center at Mount Sinai West. Given his age, and the size and the location of the hemorrhage, he scored a ‘4’ on the ICH Score, which predicts a 97 percent chance of mortality within 30 days.The physicians removed the clot within 24 hours of the hemorrhage.
“He has made a remarkable recovery,” says Dr. Kellner. “He was discharged to the rehabilitation unit at The Mount Sinai Hospital after only 10 days. Currently, he is cognitively almost back to normal, can walk with a walker, and is back to playing the piano.”
Dr. Mocco has received research grants from Penumbra, Stryker, Microvention, Medtronic, and Codman.
Updated on Dec 17, 2024 | Featured, Research, Seaver Autism Center
Joseph D. Buxbaum, PhD
Children who have older siblings or frequent interaction with grandparents are diagnosed with autism spectrum disorders (ASD) earlier than those who do not, according to new research conducted at the Seaver Autism Center for Research and Treatment at Mount Sinai, and published in the journal Autism.
The study, titled “Grandma Knows Best: Family Structure and Age of Diagnosis of Autism Spectrum Disorder,” found that about 50 percent of friends and family members reported they had suspected a child to have a serious condition before they were aware that either parent was concerned. Maternal grandmothers and teachers were the two most common relationship categories to first raise concerns. “Our work shows the important role that family members and friends can play in the timing of a child’s initial diagnosis of autism,” says Joseph D. Buxbaum, PhD, the G. Harold and Leila Y. Mathers Research Professor, and Professor of Psychiatry, Genetics and Genomic Sciences, and Neuroscience, Icahn School of Medicine at Mount Sinai, and Director of the Seaver Autism Center. He is senior author of the paper, which was published online February 8, 2017. The study included colleagues at Columbia Business School and Carnegie Mellon University.
The team conducted an online survey of 477 parents of children with autism. In addition, they carried out novel, follow-up surveys with 196 “friends and family,” who were referred by parents. Eighty percent of the children with ASD were boys, and the median age of diagnosis was 33 months. Frequent interaction with a grandmother reduced the age of diagnosis by 5.18 months, and frequent interaction with a grandfather reduced the age of diagnosis by 3.78 months. “Since early detection of ASD is critical to effective treatment interventions, we hope the study will serve as a call to action to encourage family and friends to share concerns early on,” Dr. Buxbaum says.
In other news, the Autism Sequencing Consortium, a multi-institute research group founded by Dr. Buxbaum, has received a $7 million extension of a grant from the National Institutes of Health to collect, analyze, and share samples and genetic data from people diagnosed with autism.
The Consortium now includes more than 40 international groups and 150 researchers who have generated gene sequencing data from 29,000 individuals, making it the largest such study to date in autism. All shared data and analyses are hosted on a supercomputer called Minerva, designed by Mount Sinai faculty, which enables joint analysis of largescale data. The new grant will extend the project through 2022 and expand the sample to include more than 50,000 individuals.
Updated on Jun 30, 2022 | Featured, Research
As the Zika virus continues to spread rapidly across the globe, it might pose a particular risk to people previously infected with two related viruses, dengue and West Nile, researchers at the Icahn School of Medicine at Mount Sinai have found. Their study, published in the journal Science, may help explain the severe manifestations of Zika virus infection observed in specific populations, including those in South America.
Read more about the study
Watch a video
Updated on Jun 30, 2022 | Research
Zahi A. Fayad, PhD, Mount Sinai Endowed Chair in Medical Imaging and Bioengineering, Professor of Radiology and Medicine (Cardiology), and Director of the Translational and Molecular Imaging Institute (TMII) at the Icahn School of Medicine at Mount Sinai, and the Principal Investigator of the study
Researchers at the Icahn School of Medicine at Mount Sinai have been awarded $13 million from the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) for a five-year research program that aims to uncover the mechanisms by which stress contributes to cardiovascular risk. The program aims to improve our understanding of how the effect of stress on the brain can directly impact the immune system and cardiovascular disease, and to provide a scientific platform for clinicians and researchers to integrate this knowledge into patient care.
Read the news release
Updated on Jun 30, 2022 | Featured, Research
REVEL developers Weiva Sieh, MD, PhD, left, and Joseph Rothstein, MS
Sequencing-based genetic tests are making personalized medicine a reality for patients who carry certain mutations for serious diseases, including breast and prostate cancer. Armed with information about the pathogenicity of such variants in their genome, these patients can now make proactive decisions about their health care early enough to increase the odds of success in preventing or treating disease.
But for each step forward in this new frontier of personalized medicine, physicians and scientists are stymied by their lack of knowledge about thousands of other rare variants in a patient’s genome that could also portend disease. For this reason, two researchers at the Icahn School of Medicine at Mount Sinai developed REVEL, a novel tool designed to make sense of these variants of unknown importance in order to help guide patient care and risk management and to facilitate research.
Developed by Weiva Sieh, MD, PhD, Associate Professor of Population Health Science and Policy, and Genetics and Genomic Sciences; and Joseph Rothstein, MS, an Instructor of Genetics and Genomic Sciences, and Population Health Science and Policy, REVEL is an acronym for Rare Exome Variant Ensemble Learner. The tool predicts the likelihood of whether a particular coding variant in a person’s genome is disease-causing or benign.
“REVEL is timely and significant because the number of rare variants discovered by sequencing studies is vast and growing and little is known regarding their function,” says Dr. Sieh. “Yet few pathogenicity prediction tools have targeted rare missense variants, leaving researchers and clinicians to struggle with their interpretation.” The ability to distinguish among the approximately 10,000 missense variants in each person’s genome that result in protein changes that could potentially be harmful also helps researchers set priorities for the variants they may wish to study further as new disease-causing genes. Identifying more of these variants would enable personalized medicine to realize its potential in helping more patients benefit from prevention and treatment regimens tailored to their individual disease risks.
Other tools that use different predictive features do exist, but they often do not agree with each other on the likelihood of pathogenicity. Dr. Sieh and Mr. Rothstein created REVEL as an ensemble method that uses machine learning to combine information from many of these other tools in order to generate a consensus score. REVEL incorporates 18 pathogenicity prediction scores from 13 tools, and it specializes in prioritizing the most clinically or functionally relevant variants among the sea of rare variants that are being discovered through next-generation sequencing.
