Posts Tagged ‘gene therapy’


A group of independent biologists say they plan to copy a costly gene therapy. Are they medicine’s Robin Hood or a threat to safety?

by Alex Pearlman

Citing the tremendous cost of new drugs, an international group of biohackers say they are creating a knock-off of a million-dollar gene therapy.

The drug being copied is Glybera, a gene therapy that was the world’s most expensive drug when it came on the market in Europe in 2015 with a $1 million per treatment price tag. Glybera was the first gene therapy ever approved to treat an inherited disease.

Now a band of independent and amateur biologists say they have engineered a prototype of a simpler, low-cost version of Glybera, and they plan to call on university and corporate scientists to help them check, improve, and test it on animals.

The group says it will start sharing the materials and describe their activities this weekend at Biohack the Planet, a conference in Las Vegas that hosts citizen scientists, journalists, and researchers for two days of presentations on body implants, biosafety, and hallucinogens.

“This was developed in a shed in Mississippi, a warehouse in Florida, a bedroom in Indiana, and on a computer in Austria,” says Gabriel Licina, a biohacker based in South Bend, Indiana. He says the prototype gene therapy cost less than $7,000 to create.

Experts briefed on the biohacking project were divided, with some calling it misguided and unlikely to work. Others say the excessive cost of genetic treatments has left patients without options and created an incentive to pirate genetic breakthroughs.

“It’s a fairly big deal to see biohackers turning their focus to gene therapies because the potential consequences can be quite large,” said Rachel Sachs, an associate professor of law at Washington University in St. Louis and an expert on drug pricing. “They may see themselves as serving the interests of the patient community.”

This year the Swiss pharmaceutical firm Novartis introduced another gene therapy, Zolgesma, for spinal muscular atrophy, with a price of $2.1 million. Because of the cost, some parents have struggled to obtain it for their children and the treatment is unlikely to be made available in most of the world.

Disrupting the narrative

The gene therapy that the biohackers say they are copying, Glybera, was approved for people with an ultra-rare blood disease called lipoprotein lipase deficiency. But it didn’t prove cost-effective and was pulled from the market in 2017 by its manufacturer, UniQure. To date, only one insurer, in Germany, is known to have paid for the treatment.

Andreas Stürmer, a biotechnologist and environmental engineer who is based in Linz, Austria, says after the idea of reverse engineering the treatment occurred to him he brought the concept to Licina. Their collaboration took place through Facebook messages and Skype calls, and included help from David Ishee, a biohacker in Mississippi.

In another recent example of copy-cat gene therapy, a biohacker in Florida in 2018 produced and ate an oral gene therapy for lactose intolerance using a 20-year-old scientific paper as a recipe.

“It’s about disrupting the narrative,” says Licina, also the cofounder of SciHouse, a community biotechnology lab in Indiana. “It was like, ‘Well, why not?”

One reason not to is that copying and selling the drug could infringe on UniQure’s intellectual property. Tom Malone, a spokesperson for UniQure, says the company had not been informed of the biohacking attempt. He says it still owns a patent on the drug but it does not believe there is strong demand for the treatment. “To that end, a “knock off” version of Glybera would likely face significant regulatory and commercial hurdles,” says Malone.

Also, the US Food and Drug Administration has said it is illegal to sell do-it-yourself gene therapy supplies. Still, some biohackers feel confident grabbing information from published papers, even if some of it has been patented. “This thing is protected 10 different ways,” says Ishee. “I don’t care. Because I’m not selling it.”

Get the job done

To make their knock-off, the biohackers checked the original Glybera papers for the information about the genetic sequence of the gene that patients require corrected copies of. They then placed an order with a gene synthesis company for a copy of the DNA, which was added to a circular genetic construct called a “minicircle.” When added to a cell, the mincircle will begin manufacturing small amounts of the lipoprotein lipase enzyme.

That is an important difference from the original Glybera, which employed an injection of viruses into the leg muscle to deliver the gene. Viral “delivery” is a complex undertaking but is the most commonly used strategy in gene therapy. The biohackers don’t have access to viruses because of their high cost, but say minicircles can potentially be injected, too.

Robert Kotin, an expert in gene therapy production, calls the minicircle technology controversial and says it has shown contradictory results. While minicircles, unlike viruses, could possibly be readministered time and again, they are not as efficient in getting cells to follow genetic instructions.

“It’s not the same [but] it can get the job done. It’s just less efficient,” says Ishee of the minicircles, which are based on his design. He thinks they could be injected over a period of half a year. “It’s like if you wanted to dig a swimming pool or a pond—you could buy a backhoe and dig it in a day or you could do it with a shovel at no cost over several months.”

https://www.technologyreview.com/s/614245/biohackers-are-pirating-a-cheap-version-of-a-million-dollar-gene-therapy/

Thanks to Kebmodee for bringing this to the It’s Interesting community.


A one-time intravenous infusion of the high dose of gene therapy at Nationwide Children’s Hospital in Ohio extended the survival of patients with spinal muscular atrophy type 1 (SMA1) in a Phase 1 clinical trial, according to a study.

A one-time intravenous infusion of the high dose of gene therapy extended the survival of patients with spinal muscular atrophy type 1 (SMA1) in a Phase 1 clinical trial, according to a study published in the New England Journal of Medicine. The study was conducted by Researchers from Nationwide Children’s Hospital in collaboration with AveXis, Inc. and The Ohio State University College of Medicine.

“My team at Nationwide Children’s has worked with commitment and dedication to develop a therapy that may subsequently be shown through future clinical trials to potentially alter the course of this unforgiving condition and provide a therapeutic option for the families and infants with SMA1,” says Jerry Mendell, MD, principal investigator in the Center for Gene Therapy at Nationwide Children’s.

SMA1 is a progressive, childhood, neuromuscular disease caused by a mutation in a single gene. Children with SMA1 fail to meet motor milestones and typically die or require permanent mechanical ventilation by 2 years of age. The phase 1 clinical trial is the first to test the functional replacement of the mutated gene responsible for SMA1.

A one-time intravenous injection of modified adeno-associated virus serotype 9 (AAV9) delivered the SMN gene to 15 patients. Three patients received a low dose, while 12 patients received a high dose. In the Phase 1 trial, patients in the high dose group demonstrated improvement in motor function and they had a decreased need for supportive care compared to the natural history of the disease.

Specifically, at the end of the study period, all 15 patients appeared to have a favorable safety profile and to be generally well tolerated. Of the 12 patients treated with the high dose, 92 percent of patients have achieved head control, 75 percent of patients can roll over and 92 percent of patients can sit with assistance. Seventy-five percent of these patients are now sitting for 30 seconds or longer. Two patients can crawl, pull to stand and stand and walk independently.

According to natural history of the disease, patients require nutritional and respiratory support by 12 months of age, and are not able to swallow or speak effectively. Of the patients who received the high dose in study, 11 patients are able to speak, 11 patients are fed orally and seven do not require bi-level positive airway pressure as of the data cut-off (August 7, 2017).

“In this first phase of clinical trials, we have observed preliminary results that appear to be promising compared to the natural history of SMA Type 1,” says Dr. Mendell, also a faculty member at The Ohio State University College of Medicine.

This study builds on nearly three decades of foundational research led by teams at Nationwide Children’s and Ohio State’s Wexner Medical Center and exemplifies the strong basic science and clinical bonds between the two institutions. Arthur Burghes, PhD, of Ohio State created a ground-breaking SMA mouse model that remains the standard by which all therapies, including AVXS-101, are initially tested. Senior author of the study, Brian Kaspar, PhD, during his appointment at Nationwide Children’s discovered that the AAV9 vector was capable of crossing the blood brain barrier when injected into the vascular system to deliver genes directly to motor neurons. The two laboratories then collaborated to show that scAAV9-SMN, when delivered to SMA mice shortly after birth, completely prevented their neuromuscular disorder. The laboratories also collaborated to successfully prove that reversing a protein deficiency through gene therapy is effective in improving and stabilizing SMA in a large animal model. “In neurological disease, it is rare to go from gene defect to therapy so directly, and the fact that this has happened here in one place is perhaps even rarer,” said John Kissel, MD, chair of Neurology at Ohio State and director of the SMA Clinic at Nationwide Children’s.

AveXis, Inc., a clinical-stage gene therapy company developing treatments for patients suffering from rare and life-threatening neurological genetic diseases, announced in July 2016 that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for the treatment based on preliminary clinical results from the trial of AVXS-101.

“At AveXis, we are enormously pleased to see that all children who received AVXS-101 are alive and free of permanent ventilatory support at 20 months of age and older — an age where, sadly, only eight percent of untreated children with SMA Type 1 are expected to survive without permanent breathing support,” said Dr. Kaspar, now serving as Chief Scientific Officer at AveXis. “The New England Journal of Medicine publication marks an exciting milestone in the development of AVXS-101.”

Journal Reference:

Jerry R. Mendell, Samiah Al-Zaidy, Richard Shell, W. Dave Arnold, Louise R. Rodino-Klapac, Thomas W. Prior, Linda Lowes, Lindsay Alfano, Katherine Berry, Kathleen Church, John T. Kissel, Sukumar Nagendran, James L’Italien, Douglas M. Sproule, Courtney Wells, Jessica A. Cardenas, Marjet D. Heitzer, Allan Kaspar, Sarah Corcoran, Lyndsey Braun, Shibi Likhite, Carlos Miranda, Kathrin Meyer, K.D. Foust, Arthur H.M. Burghes, Brian K. Kaspar. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. New England Journal of Medicine, 2017; 377 (18): 1713 DOI: 10.1056/NEJMoa1706198