BI Analyst Briefing: Assessing the Evolving Spinal Muscular Atrophy (SMA) Landscape

Dr. Tom Crawford has been a member of the Department of Neurology since 1987. He is co-director of the MDA clinic for Neuromuscular Disorders and Neurologist for the Ataxia Telangiectasia Clinical Center at Johns Hopkins. His practice involves general child neurology with a principal interest in caring for children with neuromuscular, neuromotor, and ataxic disorders. Primary research interests involve the basic science and clinical characterization of two important neurologic disorders that affect children: Spinal Muscular Atrophy and Ataxia Telangiectasia. He is also actively involved in the Biology of neurofilaments by characterization of transgenic animal models. He is on the Medical and Scientific Advisory Boards of Families of Spinal Muscular Atrophy, and the Medical Advisory Committee for the Muscular Dystrophy Association. He is the Neurologist for the Ataxia Telangiectasia Clinical Center at Johns Hopkins, which has evaluated almost half of the known patients with this disorder in the United States. Additional specific clinical interests include evaluation and treatment of children with brachial plexus palsies. Dr. Crawford received his medical degree from the University of Southern California. He completed a pediatric internship and residency at the Pediatric Pavilion of the Los Angeles County / University of Southern California Medical Center, followed by a pediatric chief residency. He completed his training in Neurology with Special Qualification in Child Neurology at the Los Angeles Childrens Hospital. He then traveled east to the laboratory of Dr John Griffin at Johns Hopkins for a fellowship in Neuromuscular Disorders. Prior to medical training and Neurology residency, he majored in Psychology and Religion at Yale College. Dr. Crawford has published extensively and presented nationally and internationally. He has an active role in teaching medical students and residents in neurology. In addition, Dr. Crawford has special interest and experience in EMG studies of children and adults.

Marc Engelsgjerd is the senior equity analyst for Bloomberg Intelligence specializing in the biotechnology sector. Prior to joining Bloomberg, Marc was a senior principal and oncology practice lead at inThought Research. His additional experience includes time spent in equity research at Banc of America Securities and UBS and as director of clinical affairs at Veritas Medicine, an eHealth startup. Marc earned his MD at the UCSF School of Medicine followed by residency training at the Washington University School of Medicine and Brigham and Women’s Hospital. He holds a Bachelor of Science degree in Molecular & Cellular Biology from the University of Arizona.

Sam Fazeli is a senior analyst and the EMEA head of Bloomberg Intelligence, a dynamic platform for in-depth research available on the Bloomberg Professional service at BI GO . Dr. Fazeli specializes in global pharmaceuticals. Mr. Fazeli brings with him over 22 years of experience conducting equity research as a pharmaceutical analyst, working at firms such as Nomura International and HSBC. Prior to joining Bloomberg in 2010, Mr. Fazeli worked at Piper Jaffray, Ltd. as a pharmaceutical analyst and head of European research. Before transitioning to investment banking, Mr. Fazeli was a research scientist for seven years. Mr. Fazeli has been ranked a top analyst by both the U.K. and Pan-European Extel surveys. He received a bachelor’s of science from Cardiff University, and a Ph.D. in pharmacology from the University of London.

Adrian Krainer’s lab studies the mechanisms of RNA splicing, ways in which they go awry in disease, and the means by which faulty splicing can be corrected. In particular, they study splicing in spinal muscular atrophy (SMA), a neuromuscular disease that is the leading genetic cause of death in infants. In SMA, a gene called SMN2 is spliced incorrectly, making it only partially functional. The Krainer lab found a way to correct this defect using a powerful therapeutic approach. It is possible to stimulate SMN protein production by altering mRNA splicing through the introduction into cells of chemically modified pieces of RNA called antisense oligonucleotides (ASOs). Following extensive work with ASOs in mouse models of SMA, one such molecule, known as nusinersen or Spinraza, was taken to the clinic, and at the end of 2016 it became the first FDA-approved drug to treat SMA, by injection into the fluid surrounding the spinal cord. The Krainer lab is currently using this approach for the study of other diseases caused by splicing defects, including familial dysautonomia. In addition, they are applying antisense technology to stabilize mRNAs that are destroyed by a process called nonsense-mediated mRNA decay (NMD), both to learn about the underlying mechanisms and to develop new therapies. The Krainer lab has also worked to shed light on the role of splicing proteins in cancer. They found that the splicing factor SRSF1 functions as an oncogene, and characterized the splicing changes it elicits when overexpressed in the context of breast cancer; several of these changes contribute to various aspects of cancer progression. Finally, the lab continues to study fundamental mechanisms of splicing and its regulation, and they identified novel ways in which the U1 snRNA can recognize natural 5’ splice sites that deviate from the consensus.

Dr. Rivera completed her PhD research at Columbia University Medical Center in Pathobiology and Molecular Medicine. Her work at the Center for Motor Neuron Biology and Disease focused on drug development for the neuromuscular pediatric disorder, Spinal Muscular Atrophy (SMA). Prior to Columbia, Dr. Rivera was a research associate at Cold Spring Harbor Laboratories, where she specialized in molecular research of pre-mRNA splicing mechanisms. She also earned an MBA in Finance and a Master of Science in Biophysics from the University of Barcelona.