Contents

Defy Your DNA

Table of Contents

Chapter One: Medicine on the Brink
Chapter Two: Medicine through the Millennia
Chapter Three: From Primordial Soup to Personalized Medicine
Chapter Four: Camouflage Your Genes
Chapter Five: The End of Hereditary Rare Disease
Chapter Six: New Drugs for Bad Bugs
Chapter Seven: The Big Ones
Chapter Eight: The Doctor’s Office of the Future
Chapter Nine: How Are New Drugs Regulated?
Chapter Ten: The Pharmacy of the Future
Chapter Eleven: To Infinity and Beyond

Appendices:
Bibliography: References and suggested further reading
Glossary of Terms

Preface
Some years ago, I was a family doctor in Evesham, a quaint, medieval market town on the banks of the River Avon in Worcestershire, in the United Kingdom.

As the end of my morning “surgery” approached, the phone rang. A worried patient, Mrs. Singh was hoping I could see her son, Deepak.

I describe that consultation, the worries that went through my head; the next few days as the diagnosis of Duchenne muscular dystrophy was established and the horrible task I had to face of giving a bad news to a patient and their family.

Deepak is dead now.

What more could I have done for him back then? Nothing – absolutely nothing – I couldn’t even offer hope.

That was, perhaps, the hardest lesson and most unpleasant duty I had as a family doctor.

However, in 2015, physicians will soon be able to offer more than hope to families like the Singhs.

The breakthrough comes from a new class of medicines, oligomers, that can “patch” the defective genes that cause diseases like Duchenne’s muscular dystrophy, allowing us to defy our DNA.

Bibliography:

Books
Angrist M. Here Is a Human Being: At the Dawn of Personal Genomics (Harper Collins)
Chiu LS. When a Gene Makes you Smell Like a Fish… and Other Tales about the Genes in Your Body (Oxford University Press)
Colby B. Outsmart Your Genes (Perigee)
Collins FS. The Language of Life (Harper Collins)
Davies K. The $1,000 Genome (Free Press)
Engel C. Wild Health: How Animals Keep Themselves Well and What We Can Learn From Them. (Weidenfeld and Nicolson)
Field MJ and Boat TF (Eds) – The Institute of Medicine. Rare Diseases and Orphan Products (National Academies Press)
Fields S and Johnston M. Genetic Twists of Fate (MIT Press)
Hanson W. The Edge of Medicine (Palgrave MacMillan)
Preston R. The Hot Zone (Anchor Books)
Schimpff SC. The Future of Medicine (Thomas Nelson)

Scientific journals to follow
Journal of RNAi and Gene Silencing http://libpubmedia.co.uk/RNAiJ/RNAiJHome.htm
Nature Biotechnology http://www.nature.com/nbt/index.html
Neuromuscular Disorders http://www.nmd-journal.com
Nucleic Acid Therapeutics http://www.liebertpub.com/NAT
Pharmacogenomics and Personalized Medicine http://www.dovepress.com/pharmacogenomics-and-personalized-medicine-journal

Scientific papers
Aarsma-Rus A, Janson AAM, Kaman et al. Therapeutic antisense-induced exon skipping in cultured muscle cells from six different DMD patients. Human Molecular Genetics 2003; 12 (8): 907-914

Aartsma-Rus A, van Ommen GJB. Antisense-mediated exon skipping: A versatile tool with therapeutic and research applications. RNA 2007; 13(10): 1609-1624

Cirak S, Arechavala-Gomeza V, Guglieri M et al. Exon skipping and dystrophin restoration in Duchenne Muscular Dystrophy patients after systemic phosphorodiamidate morpholino oligomer treatment. Lancet 2011; 378: 595-605

FDA. Driving Biomedical Innovation: initiatives to Improve Products for Patients. October 2011 @ http://www.fda.gov/innovation

Kole R, Krainer A, Altman S. RNA therapeutics: beyond RNA interference and antisense oligonucleotides. (Nature Reviews Drug Discovery 2012)

Schubert D, Levin AA, Kornbrust D et al. The Oligonucleotide Safety Working Group Editorial. Nucleic Acid Therapeutics 2012; 22(4): 211-212

Siva K, Covello G, Denti MA. Exon-Skipping Antisense Oligonucleotides to Correct Missplicing in Neurogenetic Diseases. Nucleic Acid Therapeutics 2014; 24 (1):69-86

Wood MJA, Gait MJ, Yin H. RNA-targeted splice-correction therapy for neuromuscular disease. (Brain 2010)

Videos about dystrophic dogs:
Untreated dog: http://www.youtube.com/watch?v=lRzBc3kvhKM
Treated littermate: http://www.youtube.com/watch?v=14VcMtpympI

Organizations
NORD: http://www.rarediseases.org
EURORDIS: http://www.eurordis.org
Muscular Dystrophy Association: http://mda.org
Personalized Medicine Coalition: http://www.personalizedmedicinecoalition.org
Parent Project Muscular Dystrophy: http://www.parentprojectmd.org
Cure Duchenne: http://www.cureduchenne.org
Action Duchenne (UK): http://www.actionduchenne.org
Progeria Research Foundation: http://www.progeriaresearch.org
General Genetics Corporation: http://www.ggcdna.com
Alnylam: http://www.alnylam.com
Isis Pharmaceuticals: http://www.isispharm.com
MAP Pharmaceuticals: http://www.mappharma.com (now part of Allergan: http://www.allergan.com )
Prosensa: http://www.prosensa.eu
Sarepta Therapeutics: http://www.sareptatherapeutics.com