This article from Acumen Journal shows how close we are to changing the way pharmaceuticals are delivered into the bloodstream. Although we have mechanical insulin pumps for more than a few years now, their mainteance, implantation, and cost, have all helped to inhibit their widespread acceptance as an alternative to daily shots. This article shows how we will be turning biology to the task and I would have to say that there are more people willing to embrace organic based nanotech... after all.. how can our own bodies hurt us?
Bioprocessing Skin Deep
You, too, can manufacture drugs.
ALEX LASH
Imagine a drug factory that never closes, takes up virtually no space, and needs no workers. Medgenics, an Israeli-U.S. biotechnology firm, is building just such a plant. But the Biopump, as its “factory” is called, is no bricks-and-mortar building—it’s a tiny patch of a patient’s own skin, genetically engineered outside the body and then reintroduced to pump therapeutic proteins into the bloodstream. The company claims that a Biopump will obviate the need for frequent injections and will avoid the dangers of gene therapy. The first clinical trial began in October.
The market for therapeutic proteins, which the Biopump would deliver, is already valued at $30 billion annually and could double by the end of the decade, according to the research firm Datamonitor. The industry is entering a critical period: dozens of drugs are in late-stage development and several key patents are due to expire and open the door to generic competition by the end of 2005, so companies are hunting for ways to distinguish their products. Several companies, including Medgenics, are racing to produce alternatives to the needle to make these drugs easier to deliver. (Disclosure: Acumen’s science editor, Barry Sherman, is a consultant for Medgenics and helped design its clinical trial.) The Biopump has roughly the dimensions of a toothpick, about 30 mm by 1 mm. The exact size and shape, as well as the precision of the proprietary tools used to harvest the skin, are crucial for allowing the piece of flesh to become a self-sustaining, histocompatible cell structure outside of the body, what Medgenics founder Andrew Pearlman calls a microörgan. It’s big enough to avoid the time-consuming process of growing a cell line but thin enough that its nutritional requirements are met through passive diffusion in a defined growth medium.
The concept grew from work at the Hebrew University of Jerusalem on the variation in the distances between animal capillaries. Once cultured in vitro, the skin sample is exposed to a standard genetic modification called transduction, in which viruses are introduced that themselves are altered to carry the gene coding for a specific therapeutic protein. In Medgenics’ current Phase 1 clinical trial, the protein is erythropoietin, or EPO, normally produced by the kidneys to stimulate red blood cell production but limited or absent in anemic people. As a treatment for patients with chronic kidney disease, EPO, sold under the names Epogen and Procrit, is already one of the most important products for the biotech giant Amgen and Ortho Biotech Products, respectively. The viruses transfer the EPO gene to the nuclei of the biopsied skin cells, turning them into protein manufacturers. Within a week, the skin patch is pumping out a therapeutic amount of protein, which is then reinserted into the patient’s body. The skin sample—essentially a biological pump—gradually reintegrates into the patient’s vascular system and skin tissue.
In traditional gene therapy, viruses are the standard transport vector, and during clinical trials, they are often injected directly into a patient and aimed at specific genes that need repair. But in one recent high-profile trial in France, the retroviral vectors went awry and triggered leukemia. The Biopump avoids this risk, because the viral-based genetic modification is done outside the body, and then the microörgan is washed clean of the virus before it is inserted.
The Biopump also delivers its drug more steadily than does a regular injection, which creates a spike in the bloodstream that then tapers off. Dr. Pearlman envisages the Biopump’s working for weeks, even months, before needing replacement. If therapy must be cut short, the pump can be removed easily.
Dr. Pearlman says that using other well-known proteins besides EPO, like interferon-alpha and human growth hormone, is within reach. “We’re not aware of any specific class or group of proteins that wouldn’t work,” he says. One limiting factor might be daily doses higher than what several implanted Biopumps could produce.
Eventually the company intends to create a system that lets nonexpert medical staff complete the entire process, from biopsy to implantation, as an outpatient procedure. If all goes well, Medgenics will produce several therapeutic proteins itself, but the explosion of proteomics means the opportunity to license the system to others for research and production of new recombinant proteins could be even greater.
