FDA Approves Therapy for Leading Genetic Killer of Infants

In a comprehensive new review article in Nature Biotechnology, Claes Wahlestedt, M.D., Ph.D., professor of psychiatry and behavioral sciences, and associate dean for therapeutic innovation, at the University of Miami Miller School of Medicine, describes the entire field of oligonucleotide therapeutics as it relates to a wide variety of disorders of the central nervous system.

DNA sequencing peaks shown on computer monitor.

The writing of the article was prompted, in part, by the December 2016 FDA approval of an entirely novel type of drug, named Spinraza, for patients with spinal muscular atrophy (SMA). SMA is a disease that robs people of physical strength by affecting the motor nerve cells in the spinal cord, taking away the ability to walk, eat, or breathe. It is the number one genetic cause of death for infants and, until now, no specific treatment was available.

An oligonucleotide drug, truly representing modern precision medicine, is a type of drug that can precisely affect the very disease-causing mechanism in SMA — and potentially in many other diseases. Indeed, there are currently many ongoing clinical trials with oligonucleotide drugs.

As initially suggested by Wahlestedt and colleagues a quarter of a century ago, through publications in journals such as Science and Nature, oligonucleotides represent viable drug candidates for the therapy of CNS disorders. In fact, as first shown by Wahlestedt and colleagues, once inside the brain, oligonucleotides can survive for long periods of time, which allows for infrequent dosing and easier treatment regimens for patients.

“A quarter of a century after our initial studies, it is very gratifying to know that patients suffering from devastating conditions are now directly benefitting from this technology,” said Wahlestedt.
Wahlestedt’s co-author is Olga Khorkova, Ph.D., who is an employee of OPKO Health, a Miami-based pharmaceutical company. OPKO, led by Phillip Frost, M.D., and Jane Hsiao, Ph.D., is using the described technology for multiple projects, including Dravet disease, a severe form of childhood epilepsy.

Tags: Claes Wahlestedt, Nature Biotechnology, oligonucleotide therapeutics, OPKO Health, spinal muscular atrophy