With scientific researchers learning more about editing human genes to treat rare diseases, a new form of medical treatment has arrived and a new process for approving those treatments is on the horizon.
That was the message from Dr. Timothy Yu, keynote speaker for the Connecticut Rare Disease Forum held Tuesday at The Jackson Laboratory for Genomic Medicine in Farmington.
The event attracted more than 235 people, including researchers and bioscience collaborators from across the state and beyond. The forum was co-hosted by BioCT, the state’s life sciences industry group.
The event opened with Lon Cardon, Ph.D., president and CEO of The Jackson Laboratory, welcoming attendees by noting that his organization is nearing its 100th birthday. He also said the lab has 90 programs researching different rare diseases and 300 different preclinical trials now underway.
Cardon noted that when he first started in the industry, developing therapies would take decades. “Now, my reading of it is somewhere between 10 months and 12 months, call it under a year,” he said. “Months from diagnosis to a treatment, not years.”
Yu, a neurologist and researcher with the Division of Genetics and Genomics at Boston Children’s Hospital and an assistant professor at Harvard Medical School, followed that with his presentation by discussing the advancements in gene splicing to treat rare disease.
He credited the impact of the Human Genome Project, which produced three main research tools that allow researchers to identify genes involved in normal biology, as well as in both rare and common diseases.
Yu said there has been a “rising tide” of identified disease genes, from just a handful in the 1980s to nearly 7,000 today — and yet fewer than 500 therapies have been produced.
The past decade has seen a lot of change, he added, including “the prospects of going directly from genetics to therapeutics.”
He cited a growing number of trials for Antisense oligonucleotide therapies, or ASOs, a class of precision medicines that target disease at its genetic source on a more individualized basis for each patient.
These lab-made strands bind to RNA — the instructions for making proteins — and can block or alter faulty messages before harmful proteins are produced. By intervening early in the process, ASOs aim to treat the underlying cause of disease rather than just its symptoms, particularly in rare genetic disorders.
Yu said that, to date, there are 35 ASO trials involving 82 patients, treating diseases of the brain, spinal cord, liver and eye.
The momentum in this field is really helpful, he said.
“It’s calling for a new specialty, something that we call ‘interventional genetics,’ this practice of bringing together the genetics for diagnosis and discovery… with the tools to intervene around a careful and ethically thoughtful approach” to treating patients.
With such treatments being specifically created for individual patients, there is also a growing movement to drastically alter the way regulators approve them.
The United Kingdom, for example, has launched a pilot program for approvals based on the “do & tell” regulatory model, Yu said.
That model is where a doctor acts in the patient’s interest in clinical timelines, but then reports back to the regulatory agency “a comprehensive list of all activities done that can be audited and reviewed to support further adaptation,” he said.
The U.S. Food and Drug Administration (FDA) has agreed to consider such a model, Yu said, citing a statement from the agency in November that said, “Once a manufacturer has demonstrated success with several consecutive patients with different bespoke therapies, the FDA will move towards granting market authorization for the product.”
Cat Lutz, Ph.D., vice president of the JAX Rare Disease Translational Center at The Jackson Laboratory, said the regulatory climate has grown increasingly difficult under the current administration in Washington, D.C.
“The lack of stability in the FDA has really, I think, caused a lot of uncertainty, and it has probably caused a lot of investors to hang back a little bit to look to see how that’s going to stabilize.”
Yu said the FDA considering an alternative approach to approving bespoke therapies is a step in the right direction. He noted that if a doctor can decide to do heart surgery on an infant born with a life-threatening condition to save its life, the same should be true for what he called “genetic surgery.”
“Can we use that approach … to analyze the deep technical requirements for intervention and to deliver a custom genomic intervention?” he asked.
