Updated on Jun 30, 2022 | Featured, Research
Aaron E. Miller, MD, left, and Fred D. Lublin, MD, helped lead groundbreaking multiple sclerosis research.
Three multicenter Phase III trials in which Mount Sinai researchers played key roles have reported highly encouraging results for the investigational drug ocrelizumab in treating both primary progressive multiple sclerosis (MS), the most disabling form of the disease, as well as relapsing MS, the most prevalent form. Two of the three trials, known as OPERA I and OPERA II, were focused on relapsing MS. The third trial, ORATORIO, was aimed at primary progressive MS. The findings were published online Wednesday, December 21, 2016, in The New England Journal of Medicine (NEJM). “The results for ORATORIO were truly groundbreaking because we never before had a treatment that was proven to work with primary progressive MS,” says Aaron E. Miller, MD, Professor of Neurology at the Icahn School of Medicine at Mount Sinai and Medical Director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai. “In the case of relapsing MS, we have had many options in the past, but this new treatment has extremely good efficacy and will probably be widely used for patients with the disease.”
MS is a complicated, often disabling, disease of the central nervous system that can produce a wide variety of neurological symptoms as it disrupts the flow of information within the brain and spinal cord, and between the brain and body. It afflicts an estimated 2.3 million people worldwide and 400,000 in the United States. Approximately 10 to 15 percent of this population is diagnosed with primary progressive MS, in which patients, instead of relapsing and recovering partly or fully, experience gradual deterioration from disease onset.
According to Dr. Miller, who served as principal investigator at Mount Sinai for ORATORIO, ocrelizumab significantly reduced the progression of clinical disability of primary progressive MS at both 12 and 24 weeks—a finding that prompted the NEJM to hail the trial in an editorial as a “landmark study in the field.”
Fred D. Lublin, MD, Saunders Family Professor of Neurology at the Icahn School of Medicine at Mount Sinai and Director of the Corinne Goldsmith Dickinson Center, was a member of the steering committee that designed and monitored ORATORIO. Dr. Lublin was also an author for OPERA I and OPERA II, which found that ocrelizumab resulted in 46 to 47 percent lower relapse rates than interferon beta-1a, a current leading treatment for relapsing MS. Ocrelizumab, from Genentech, a member of the Roche Group, was created to treat both forms of the disease. A humanized monoclonal antibody, ocrelizumab binds to CD-20 proteins on the surface of certain B cells, causing their depletion. B cells are believed to be a key contributor to attacks on the insulation and support around nerve fibers in the brain, spinal cord, and optic nerves that can lead to disability. Ocrelizumab is administered by intravenous infusion every six months.
“Every study brings us closer to a cure, and now we have opened the door to a whole new group: patients with primary progressive MS, whom we can more successfully treat,” Dr. Lublin says. “The next challenge is to see if we can select patients most likely to respond to this therapy.”
Updated on Jun 30, 2022 | Research
Fred Lublin, MD, director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis
As many as 400,000 Americans are believed to suffer from multiple sclerosis — a debilitating disease of the central nervous system. A new drug may provide relief from the most devastating form of MS. Fred Lublin, MD, director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at The Mount Sinai Hospital, worked on the trial.
Updated on Jun 30, 2022 | Featured, Research
Even before tumors develop, breast cancer cells with a few defined molecular alterations can spread to organs, remain quiet for long periods of time, and then awaken to form aggressive, deadly breast cancer metastasis, says a team of investigators led by researchers at Icahn School of Medicine at Mount Sinai and the University of Regensburg in Germany.
Updated on Jun 30, 2022 | Featured, Research
Ilana Katz Sand (right) is trying to see whether dietary changes can benefit her patients.
An article published online November 30 in Nature discusses how dietary changes may be able to alleviate the symptoms of multiple sclerosis. Research by Ilana Katz Sand, a neurologist and MS specialist at The Mount Sinai Hospital, is featured
Updated on Jun 30, 2022 | Featured, Inside, Psychiatry, Research
René S. Kahn, MD, PhD
Two world-renowned researchers in brain disease have assumed key leadership roles at the Icahn School of Medicine at Mount Sinai: René S. Kahn, MD, PhD, as Chair of the Department of Psychiatry, and Paul Kenny, PhD, as Chair of the Department of Neuroscience. Both men have made significant academic and scientific achievements in their respective fields. Dr. Kahn, the newly appointed Esther and Joseph Klingenstein Professor of Psychiatry, has dedicated his career to studying psychotic disorders, particularly the origins and treatment of schizophrenia. Dr. Kenny, Ward-Coleman Chair in Pharmacology and Experimental Therapeutics, has focused on understanding the neurobiological mechanisms of drug addiction, obesity, and schizophrenia, and developing novel therapeutics that address each.
Dr. Kahn returns to the Mount Sinai Health System after more than 20 years. Most recently, he served as Professor of Psychiatry and Director of the Brain Center Rudolf Magnus at the University Medical Center Utrecht in the Netherlands. The author of 800 research papers and book chapters, he has made major findings that have helped inform clinical work in the field. One of his seminal discoveries was that schizophrenia starts in the early teenage years, earlier than previously thought, and that the first cognitive symptoms usually precede the first psychosis and visit to the psychiatrist by 10 years. “This is very important because we now know if we want to understand the illness and identify people at risk, we have to look much earlier in the process,” says Dr. Kahn.
Using neuroimaging, Dr. Kahn has uncovered progressive changes in the brain over the course of schizophrenia that are linked to its severity. In his new role as Chair, he plans to establish a high risk clinic to identify and treat individuals at an early age who are likely candidates for a range of psychiatric illnesses, as well as drug abuse. “A specialized clinic of this type will have a major impact scientifically, as well as on the overall health care system, and New York’s population, in particular,” he says.
A member of the Royal Netherlands Academy of Science and a former Fulbright Scholar, Dr. Kahn completed a four-year psychiatry residency at The Mount Sinai Hospital and was appointed to the Icahn School of Medicine at Mount Sinai faculty in 1992. He conducted schizophrenia research and served as Research Unit Chief at the James J. Peters VA Medical Center in the Bronx, before returning to the Netherlands. For two decades, Dr. Kahn has maintained an adjunct appointment at Mount Sinai to continue his collaborations with faculty members.
“I am delighted that Dr. Kahn is joining us,” says Kenneth L. Davis, MD, President and Chief Executive Officer of the Mount Sinai Health System. “His medical acumen is evidenced by the honors and accolades awarded to him through his noteworthy career.”
Paul Kenny, PhD
When Dr. Kahn received an endowed professorship at Mount Sinai’s Convocation Ceremony in September, he told the audience that his mentors were Dr. Davis and Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, and President for Academic Affairs, Mount Sinai Health System, both of whom have made significant discoveries in neuroscience.
“My two mentors are together,” he said, “having built one of the best medical schools in the United States and probably the world, and I am extremely honored to be part of that.”
Dr. Kenny is a world authority on the neurobiology of addiction and obesity and has advanced the scientific community’s understanding of the mechanisms of both disorders. His recent work in tobacco addiction has centered on a group of proteins known as nicotinic acetylcholine receptors (nAChRs) that consist of five subunits, each encoded by its own unique gene. (Previous research by a Mount Sinai scientist identified a mutation in one of those genes, CHRNA5, which appears to influence whether someone becomes a smoker, and the severity of his or her habit.)
“My lab played an important role in understanding how the CHRNA5 gene works, and that has opened a new window on nicotinic-receptor signaling in the brain and how it influences behavior,” says Dr. Kenny. People who carry CHRNA5 variants are more likely to smoke, not because they enjoy nicotine more than others, but because they are resistant to adverse effects of the drug, according to his team’s findings.
The Kenny Laboratory is currently investigating the molecular and cellular mechanisms of CHRNA5 in nicotine addiction and also developing novel smoking-cessation therapeutics based on a better understanding of how this gene variant works.
His interests also include the role for novel regulatory RNA elements in brain cells called microRNAs in drug addiction and schizophrenia. Dr. Kenny says, “We were among the first to show that microRNAs in the brain can influence behavior and may play a role in various aspects of neuropsychiatric disorders.” Under Dr. Kenny’s direction, Mount Sinai’s Experimental Therapeutics Institute is actively exploring the novel therapeutic potential of microRNAs.
“Dr. Kenny is an international authority on applying the tools of molecular biology to neuropharmacology and using the new insights obtained to develop novel treatments for neuropsychiatric disorders. He has served as an inspiring leader of Mount Sinai’s Experimental
Therapeutics Institute, and the Department of Neuroscience will be fortunate to benefit from his innovative leadership,” says Eric J. Nestler, MD, PhD, Nash Family Professor of Neuroscience, Director of The Friedman Brain Institute, and Dean for Academic and Scientific Affairs at the Icahn School of Medicine at Mount Sinai.
Prior to joining Mount Sinai in 2013, Dr. Kenny served as Associate Professor of Molecular Therapeutics, and Director of the Medications Development Program in Substance-Related Disorders at The Scripps Research Institute’s Jupiter, Florida, campus. He completed his doctorate in Neuroscience at King’s College London, and pursued his postdoctoral training at The Scripps Research Institute in La Jolla, California.
