2016 Archived Content

Strategies for Tackling Rare Genetic Diseases Header

According to the National Institutes of Health, there are nearly 7000 rare diseases and more than 25 million Americans are suffering from one of them. Approximately 80% of these rare diseases are genetic in origin. Cambridge Healthtech Institute’s symposium on Strategies for Tackling Rare Genetic Diseases will bring together leading scientists, clinicians, executives and experts who are deeply involved in bringing to market the treatments for such rare genetic disorders. This symposium will highlight scientific breakthroughs, use of innovative technologies and approaches to tackle translational challenges and bring together the right mix of people to discuss potential opportunities in this field.

Final Agenda


• September 19 Symposium: Strategies for Tackling Rare Genetic Diseases

• September 20-21 Conference: Gene Therapy Breakthroughs

• September 21-22 Conference: Translating Cancer Genomics

Monday, September 19

7:00 am Registration Open and Morning Coffee


8:30 Chairperson’s Opening Remarks

Colin Nichols, Ph.D., Carl Cori Professor in Cell Biology and Physiology, and Director of the Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine

8:40 Gene Therapy for Lysosomal Storage Diseases

Christian Hinderer, Ph.D., Post-Doctoral Fellow, Laboratory of Dr. James Wilson, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania

Enzyme replacement therapies have revolutionized the treatment of many lysosomal storage diseases (LSDs). However, the central nervous system manifestations of these disorders remain difficult to address due to the challenges of protein delivery beyond the blood-brain barrier. Using adeno-associated virus vectors to deliver genes encoding lysosomal enzymes to the CNS, we have developed a platform for efficient, long-term correction of CNS pathology associated with LSDs.

9:10 Messenger RNA (mRNA) Therapeutics for the Treatment of Rare Diseases

Ron Lahav, Ph.D., CEO, ART Bioscience Ltd.

The supplementation of proteins that are not expressed or are not functional is the most obvious application for mRNA-based drugs. The development of mRNA-based therapeutics is being accelerated by companies such as BioNTech and Moderna, which are supported by considerable venture capital inflows. The production of mRNA-based drugs is highly flexible, and represents a truly disruptive technology that may revolutionize the therapeutic intervention of diseases in general, and Duchenne Muscular Dystrophy (DMD) in particular.

9:40 Superior Effects of GSK-3 Inhibitors in the Treatment of Brain Cancers

Alan P. Kozikowski, Ph.D., Professor, College of Pharmacy, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago and Actuate Therapeutics Inc.

Glioblastoma multiforme (GBM), also known as glioblastoma and grade IV astrocytoma, is the most common and aggressive of all brain cancers. Given the difficulty in treating GBM tumors, better agents are clearly needed. Here I disclose our results with a GSK-3 inhibitor to potentiate the inhibitory effects of irinotecan in PDX orthotopic xenografts. The results are fascinating and have led to orphan drug status approval with the FDA.

10:10 Coffee Break


10:40 A Drug Algorithm Decision Matrix Designed to Identify and Assemble a De-Risked Therapeutic Pipeline

Rachel Salzman, DVM, CSO, The Stop ALD Foundation

The ALD Connect consortium of researchers, clinicians, industry, and patient advocacy have established a robust algorithm for identifying promising preclinical and clinical agents in order to determine where and how limited resources and attention should be focused within the adrenoleukodystrophy and adrenomyeloneuropathy therapeutic pipelines. This process also identifies pre-competitive opportunities and laboratory workflow plans that will benefit multiple sponsors. This process can be applied to almost all rare genetic diseases.

11:10 Precision Medicine: Personalized Proteomics for the Diagnosis and Treatment of Idiopathic Inflammatory Disease

Vinit Mahajan, M.D., Ph.D., Assistant Professor of Ophthalmology and Visual Sciences, University of Iowa College of Medicine

A patient’s genetic profile often does little to improve treatment in the near-term. To address an inherited inflammatory disease, we took a personalized proteomics approach using liquid biopsies of the diseased organ. Our proteomic analysis identified specific pathological cytokines and guided a targeted treatment with approved therapeutic drugs. Personalized therapy reversed the vision loss, illustrating how proteomics replaced a trial-and-error approach.

11:40 Enjoy Lunch on Your Own


1:40 Chairperson’s Opening Remarks

Ronald Alfa, M.D., Ph.D., Director, Translational Biology, Recursion Pharmaceuticals LLC

1:50 Chemogenomic Screening to Identify New Targets for Rare Diseases

Lyn Jones, Ph.D., Head of Rare Diseases Chemistry and Chemical Biology Group Leader, Pfizer Worldwide Medicinal Chemistry

Bioinformatics analyses and computational chemistry techniques, combined with crowdsourcing efforts and human curation, were used to create a chemogenomic library (CGL) of well-defined, selective small molecule pharmacological agents that cover a significant number of biological targets. The CGL was screened in a phenotypic assay relevant to the treatment of myotonic dystrophy to identify potential therapeutic opportunities.

2:20 Repurposing as a Source of Chemical Probes for Target Identification

Paul C. Trippier, Ph.D., Assistant Professor in Pharmaceutical Sciences at the Texas Tech University Health Sciences Center School of Pharmacy

The neuronal ceroid lipofuscinoses (NCLs), although rare, are the most common neurodegenerative disorders of childhood. These diseases have poorly understood pathophysiology and no validated targets making for a highly challenging landscape for drug discovery. A unique library of designed chemical probes demonstrate protective effects in NCL phenotypic cell lines. We are employing these probes to identify targets of action for continued therapeutic development.

2:50 Whole Organism Repurposing Drug Screening Brings Forward Novel Targets for Spinocerebellar Ataxia Type 3

Patricia Maciel, Ph.D., Associate Professor and Senior Researcher at the School of Health Sciences of the University of Minho, Braga, Portugal

We have performed a motor phenotype-based screening of a library of mostly FDA-approved compounds in a C. elegans model of Spinocerebellar ataxia type 3 and identified several promising compounds, with effect on behavior but also mutant protein aggregation. The SSRI citalopram was validated as a very promising therapeutic compound in worm and mouse models, and serotonin signaling was proven to be a major modifier of SCA3 pathogenesis.

3:20 Refreshment Break


4:00 Rare Disease Drug Discovery at Scale

Ronald Alfa, M.D., Ph.D., Director, Translational Biology Recursion Pharmaceuticals LLC

Drug discovery is typically thought of as a precise and targeted evaluation of potential chemical modifiers of specific targets or phenotypic indicators related to human disease. I will explore alternative systems in which rapid advances in technology can be leveraged to parallelize drug discovery. A relatively in-depth look at Recursion’s take on such a system, as well as specific examples of our diverse successes will be discussed.

4:30 Cantu Syndrome: Cardiovascular Complexity and Complications Revealed in a Sentinel Monogenic Disease

Colin Nichols, Ph.D., Carl Cori Professor in Cell Biology and Physiology, and Director of the Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine

Cantu Syndrome is caused by mutations in two genes that underlie cardiovascular KATP channels. Disease features are manifold, ranging from hypertrichosis, to cardiomegaly, to low blood pressure, persistent PDA, migraine and lymphedema. To understand how the features arise, and to develop therapy for this and other diseases with such features, we have assembled a team of basic scientists, clinicians and drug discovery experts. These channels are targets of sulfonylurea drugs, bringing the chance for both new and already approved drugs to be used.

5:00 Drug Repurposing as a Strategy to Improve Patient Outcomes

Clare Thibodeaux, Ph.D., Director of Scientific Affairs, Cures Within Reach

Drug repurposing is a critical aspect of treating rare diseases, where basic research has lagged behind therapeutic impact. Cures Within Reach has been catalyzing repurposing research to improve patient outcomes since 2010. This presentation will highlight the repurposing research process, including questions to ask when evaluating a potential research project, strategies for bringing the different stakeholders together and success stories in rare diseases.

5:30 Close of Symposium

* Separate registration required for Short Courses, Symposia, Training Seminar