[Corrected, 10/24/16, 2:44 p.m. See below.] In 2009, Jennifer Adair was helping treat a brain cancer patient in an experimental study. The trial required genetic modification of the patient’s blood stem cells in a specialized sterile room at Seattle’s Fred Hutchinson Cancer Research Center, where Adair is a gene therapy researcher. Over the course of four days, Adair and her colleagues followed strict anti-contamination procedures, stripping off gowns when they stepped out for a meal or a bathroom break, then washing up and “gowning in” again to re-enter the room.
There has to be a better way, she thought. What if the same procedure could take place faster and in any clinic, not just a multimillion-dollar facility with a dozen or more highly trained workers? Her idea was bolstered by experiences working with HIV, which is also a target of experimental gene therapy that, if ever approved, would have a hard time reaching millions of people who need it.
Adair (pictured) set out to build what she calls “gene therapy in a box”—a benchtop system that could automate many of the tasks now performed in only a handful of clean rooms around the world. She and her colleagues have tested the machine—it looks a bit like R2-D2’s head—on mice and a few monkeys, showing that the system stayed sterile and modified enough cells to help the animals restart healthy blood production. The work was published today in the journal Nature Communications.
It’s a first step, but one of several required to convince medical regulators that the tabletop system can be used to test gene therapy in humans, which Adair thinks could happen next year in collaboration with an under-the-radar biotech company in New York City.
“This would represent a significant leap forward for gene therapy if brought to bear,” says Brian Sorrentino, a doctor at St. Jude Children’s Research Hospital in Memphis, TN, who treats patients with stem cell gene therapies produced in St. Jude’s 60,000-square-foot clean room. “It’s almost like being a surgeon in an operating room, except here we’re operating on cells. Sometimes it’s quite difficult to do. This system offers the potential to automate the entire process,” says Sorrentino, who is familiar with Adair’s work but was not involved.
[This paragraph has been changed to clarify the difference between the original and modified versions of the Prodigy device.] Adair has collaborated with the German medical equipment maker Miltenyi Biotec, whose blood-separation devices and reagents are used widely in labs, to modify a $150,000 box called Prodigy. The original device takes in a patient’s blood or bone marrow, separates out the stem cells, and pumps the cells into an IV bag that can be brought back to the patient. Adair’s modified version can also make genetic modifications to the stem cells.
The blood disorders sickle cell disease and beta-thalassemia are among myriad diseases that might be corrected by knocking out or correcting genes in a person’s hematopoietic stem cells (HSCs), which live in the bone marrow and produce all the specialized cells that make blood. There is also the possibility of modifying HSCs to help cancer patients withstand toxic chemotherapies—the reason Adair was working on the brain cancer trial back in 2009.
If all goes well, the first group of people to receive tabletop gene therapy in a clinical trial would be patients with Fanconi anemia, a rare genetic bone marrow failure that causes a host of serious physical abnormalities and a higher risk of cancer. The only known cure is a bone marrow transplant from a matching donor, such as a sibling.
Rocket Pharmaceuticals in New York has been funding Adair to come up with a special “kit”—including the disposable components and the chemicals needed to genetically modify the cells. Reached at a conference in Italy, Rocket executives told Xconomy they hope to start a trial for Fanconi patients in 2017 if regulators approve the kit. The FDA has already approved the Prodigy machine, according to Adair.
The Rocket team declined to say how much funding they have provided to the lab. They also declined to comment about their only regulatory filing to date, which showed in January 2016 that the company had raised more than $16 million in a potential $38 million offering.
Adair and her coauthors report the cost of the kit used in the experiments as $26,000, but she and Rocket executives say it’s too early to determine real-world costs per patient—they would “be specific to the disease being treated,” Adair says.
Those costs—whatever they turn out to be—when added to the price of a Prodigy machine, would represent a razor-and-blade business model, with the box the one-time outlay. “150,000 dollars seems steep, but a GMP [manufacturing] facility costs millions of dollars to build and run,” says Matthew Porteus, a Stanford University doctor who
