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Highlighting Innovation for Rare Disease Therapies at Boston Children's Hospital


Boston Children's Research Showcase and Networking Reception:

Advancing the Development of Rare Disease Therapies

In May we co-hosted a Boston Children’s Rare Disease Networking Event with the Manton Center at MassBio Headquarters in Cambridge. The event was a success with over 100 attendees from industry, Boston Children's, and other academic institutions. The evening featured a lively panel with David Williams, MD (Chief Scientific Officer and Senior VP of Research, Chief of Hematology/Oncology), Wayne Lencer, MD (Chief of Gastroenterology, Hematology and Nutrition), Philip Reilly, MD, JD (Venture Partner of Third Rock Ventures), and Alvin Shih, MD (CEO of Enzyvant). Additionally, Mustafa Sahin, MD, PhD (Director of the Translational Neuroscience Center), Vijay Sankaren, MD, PhD (Division of Hematology/Oncology Research), and William Pu, MD (Division of Cardiology) presented lightening talks of their ongoing rare disease research. We plan to host two additional Boston Children’s showcase events with MassBio over the next year. The next event, highlighting neurological disorders, will take place on November 28th - mark your calendars and look out for more information!


Boston Children's Rare Disease Partnering Opportunities:

There are approximately 7,000 rare diseases affecting 1:10 Americans; however, 95 percent of rare diseases do not have an FDA approved treatment. Boston Children’s Hospital and its Manton Center for Orphan Disease Research are at the forefront of conducting research to identify, understand, diagnose and treat these diseases across all clinical fields, including hematology, oncology, pulmonary, cardiology, neurology and more. Below are some innovations available for partnership and licensing:

Targeted therapy for catecholaminergic polymorphic ventricular tachycardia (CPVT)CPVT is the inherited arrhythmia for which current standard of care is least successful. There are both treatment failures, often with tragic consequences, and treatment-related adverse events. William Pu, MD (Division of Cardiology) and his colleagues have studied the mechanism by which exercise induces arrhythmia in CPVT patients and they have identified an essential molecular pathway and shown that inhibition and/or mutation of this pathway ininduced-pluripotent stem cell-derived cardiomyocytes from CPVT patients blocks their arrhythmic phenotype. Currently, they are testing a gene therapy approach to inhibit this pathway in a mouse model of CPVT. Preliminary results have supported the utility of this strategy to suppress arrhythmia in vivo, which may also be effective for broader arrythmia diseases.

High-throughput zebrafish platform for epileptic encephalopathy genes. Annapurna Poduri, MD, MPH (Epilepsy & Clinical Neurophysiology) and her team have developed a high-throughput zebrafish platform to discover epilepsy-causing genes. Specifically, they study epileptic encephalopathies, rare neurological disorders in which where newborns and infants can experience many seizures per day, with often-severe neurodevelopmental consequences. Typically, there is no cure for these diseases, and a better understanding of their genetic underpinnings would inform diagnosis and treatment options. After knocking out suspected genes in zebrafish, high-throughput phenotypic screening is performed to identify genes with a clear role in epilepsy. Dr. Poduri and her team have identified seizures in several genes to date with this method, and they are currently validating them. The group will also use this high-throughput platform for drug screening, which can hopefully be translated back into the clinic to treat genetic epilepsies. 

Treatment for myotonic dystrophy. Myotonic dystrophy is an autosomal dominant multi-system disorder that affects the skeletal muscles, central nervous system, heart, pancreas, and eyes. It is a life-threatening disease for which no definitive therapy has been discovered. Myotonic dystrophy type 1 (DM1) is caused by repeat expansion in the DMPK gene. This mutant RNA binds and sequesters the MBNL1 protein, leading to aberrant splicing of its downstream RNA targets. Researchers at Boston Children's, led by Lou Kunkel, PhD (Genetics), are collaborating with researchers at Tufts university, led by Isabelle Draper, PhD, to identify small molecules that target this pathway disruption. They have identified a compound, ascochlorin (ASC), which triggers an elevation in the levels of MBNL1 and rescues aberrant splicing of DM1 biomarkers. As next steps, they plan to optimize ASC derivatives and test them in relevant in vitro and in vivo assays.

For more information on these and other Boston Children's opportunities, please email TIDO and search our technologies online


Clinical Highlight: Clinical Trials for Gene Therapy to Treat Blood Diseases, led by David A. Williams, MD
Senior Vice President and Chief Scientific Officer, Chief of the Division of Hematology/Oncology, Boston Children’s Hospital; President, Dana/Farber Boston Children’s Cancer and Blood Disorders Center; Leland Fikes Professor of Pediatrics, Harvard Medical School)

For decades, Dr. David Williams and his colleagues have focused on diseases affecting the stems cells responsible for normal development of blood. Now, that knowledge is being translated into genetic therapies to treat those diseases. Dr. William’s efforts have culminated in the launch of several clinical trials for rare pediatric blood diseases at the Dana-Farber/Boston Children’s Hospital Cancer and Blood Disorders Center.

Early uses of gene therapy to treat blood diseases in mouse models and human clinical trials demonstrated that transplantation of genetically-modified stem cells leads to production of functional white blood cells. However, several of these early studies were complicated by the development of leukemia or leukemia-like growth of the blood cells in multiple patients.

After several years of basic research and development, Williams and other scientists mapped the genetic elements leading to these leukemias. By using this knowledge they engineered new vectors to limit when and where genes are targeted or expressed, lowering the risk for complications.

The Gene Therapy Program at Boston Children’s/Dana-Farber Cancer Institute, under the leadership of Drs. Alessandra Biffi and Sung-Yun Pai, has grown substantially over the past 5 years. Ongoing studies, being conducted at Boston Children's and partnering hospitals, are treating X-linked chronic granulomatous disease (X-CGD), X-linked severe combined immunodeficiency (SCID-X1), Wiskott-Aldrich Syndrome, and cerebral adrenoleukodystrophy (CALD; sponsored by bluebird, Inc.). A forthcoming study, slated to begin this year, will treat sickle cell disease. Promising early results have already been reported for SCID-X1 and CALD.

While gene therapy is still in its infancy, these groundbreaking studies give hope to thousands of patients still waiting for treatments of their rare genetic diseases.

TIDO's Annual Report for
Fiscal Year 2016

The annual report provides information on selected FY16 licenses and collaborations, Technology Development Fund award winners, startups and selected technologies available for licensing.  [Download Here]

Newly Issued Patents
Available for Partnering


Umut Ozcan | US 9,730,985 |
Method of reducing blood glucose


Denisa Wagner | US 9,642,822 |
Methods for treating and preventing neutrophil-derived net toxicity and thrombosis

Jonathan Kagan | US 9,650,427 |
Modulators of antiviral signaling pathways
and therapeutic uses thereof

Dale Umetsu | US 9,657,046 |
Methods for the treatment and prevention of inflammatory diseases

Dale Umetsu | US 9,683,049 |
Modulation of TIM receptor activity in combination with cytoreductive therapy

Stephen Harrison | US 9,718,873 |
Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza hemagglutinin


George Daley
| US 9,670,463 |
Inhibition and enhancement of reprogramming
by chromatin modifying enzymes

Carlo Brugnara | US 9,678,088 |
Multiphase systems for diagnosis of sickle cell disease

Leonard Zon | US 9,683,995 |
Method of treatment of SETDB1 expressing cancer

Judy Lieberman | US 9,689,040 B2 |
Selective inhibitors of tumor-initiating cells

Leonard Zon | US 9,737,567 |
Method of enhancing hematopoietic 
stem/progenitor cell engraftment

Vascular Biology

Joyce Bischoff
 | US 9,737,514 |

Methods and compositions for the treatment
of proliferative vascular disorders

Selected Recent Publications on 
Rare Diseases

Cao S, Smith LL, Padilla-Lopez SR, et al. Homozygous EEF1A2 mutation causes dilated cardiomyopathy, failure to thrive, global developmental delay, epilepsy and early death. Hum Mol Genet. 2017; 26 (18): 3545–52. doi: 10.1093/hmg/ddx239

Grant S, Faraoni D, DiNardo J, Odegard K. Predictors of Mortality in Children with Pulmonary Atresia with Intact Ventricular Septum. Pediatr Cardiol. 2017. doi: 10.1007/s00246-017-1706-6. 

Agarwal PB, Wang R, Li HL, et al. 
Epithelial Sodium Channel ENaC is a Modifier of the Long Term Non-progressive Phenotype Associated with F508del CFTR Mutations. Am J Respir Cell Mol Biol. 2017. doi: 10.1165/rcmb.2017-0166OC.

Ong MS, Mullen MP, Austin ED, et al. Learning a Comorbidity-Driven Taxonomy of Pediatric Pulmonary Hypertension. Circ Res. 2017; 121(4):341-353. doi: 10.1161/circresaha.117.310804

Vieira NM, Spinazzola, JM, Alexander MS, et al. Repression of phosphatidylinositol transfer protein α ameliorates the pathology of Duchenne muscular dystrophy. PNAS. 2017;114(23):6080-85. doi: 10.1073/pnas.1703556114. 

Biffi A. 
Hematopoietic Stem Cell Gene Therapy for Storage Disease: Current and New Indications. Mol Ther. 2017. 3;25(5):1155-1162. doi: 10.1016/j.ymthe.2017.03.025. 

Bialas AR, Presumey J, Das A, et al. 
Microglia-dependant synapse loss in type I interferon-mediated lupus. Nature. 2017; 546: 539–543. doi:10.1038/nature22821 

LaQuaglia MJ, Grijalva JL, Mueller KA, et al. 
YAP Subcellular Localization and Hippo Pathway Transcriptome Analysis in Pediatric Hepatocellular Carcinoma. Sci Rep. 2016 Sep 8;6:30238. doi: 10.1038/srep30238.