MGVS head Dr. Moshe Flugelman: We can enlarge these arteries and prevent the need for amputation.When two middle-aged American men paid a visit to doctors at the University of Michigan Medical Center in Ann Arbor, they could barely walk for more than five to six minutes at a time. Both men, in their 50s, suffered from blocked arteries in their legs, and traditional therapies like balloons or stents could not help. In the normal course of events, the two were likely to lose their legs.
Instead they took part in a trial of a new form of cell therapy developed by Israeli company, MultiGene Vascular Systems (MGVS), and rather than lose a limb, both men are now up and about, walking in a way they haven’t managed for years.
“Before the procedure both men could hardly walk and were at risk of a leg amputation. After the treatment we tested how far they could walk and both had improved their walking beyond our expectations. They did very well,” says Dr. Moshe Flugelman, a cardiologist for over 30 years and the CEO of Haifa-based MGVS.
Some 12 million people suffer from blocked arteries or peripheral arterial disease (PAD) in the US alone, often caused by health problems such as diabetes, high blood pressure, high cholesterol, obesity and smoking. While there are some treatments available on the market today – including angioplasty, atherectomy, or bypass – not all patients can be treated, and many of these end up with critical limb ischemia (CLI). Almost 70,000 amputations are performed each year as a result.
Through his own work, Flugelman understood the tremendous cost of these amputations to both patients and the health service alike and decided to use his expertise to try to develop a new kind of cell therapy that could help patients and dramatically reduce the number of amputations.
The resulting cell-based therapy, MultiGene Angio (MGA), harnesses cells taken from the patient’s body (sometimes a 10 cm. vein segment stripped from under the arm), activates them with the insertion of specific genes in a lab, and injects them back into the patient’s artery.
These new empowered cells are designed to trigger angiogenesis, improving blood flow to the leg, arm, or heart – in the case of patients with blocked coronary arteries – by causing small blood arteries to expand and grow, bypassing the blocked arteries.
“Everyone develops some collateral arteries, even those with gangrene who will eventually have to undergo amputation,” Flugelman tells ISRAEL21c. “We can enlarge these arteries and prevent the need for amputation.”
The cell transfer approach is unlike other cell therapies because – as the name suggests – it uses several cells activated by gene transfer to mimic the normal process of blood vessel formation and remodeling. “We try to mimic mother nature,” says Flugelman. “We expand the natural process.”
Unlike traditional therapies that rely on dramatic surgical intervention, such as bypass surgery, stents, or balloons, which are not suitable for patients with small arteries, this therapy requires less invasive surgery. The cells taken from the patient’s body are removed with local anesthetic. The whole treatment can be done in an outpatient’s clinic.
Recovery is longer than for the more radical methods. It takes four weeks to produce new cells, but instead of spending days recuperating in hospital, the patient can go home after several hours.
Flugelman came up with the idea for his new therapy when he returned to Israel after several years in the US. During his time there he had been involved in gene therapy, and wanted to continue his research in this field.
“I realized early on that I couldn’t compete with the big labs, and that I’d have to be more creative and think ahead of everyone else,” says Flugelman. “That’s how we came up with the idea of using more than one cell type and more than one gene to accomplish the complex processes we see in the body.”
He founded MGVS in August 2000 with Dr. Basil Lewis, the director of the department of cardiovascular medicine at the Carmel Medical Center, at the Naiot incubator.
Two years later the company left the incubator and opened offices at the Carmel Medical Center in Haifa.
“It’s very uncommon to have a startup company working within a hospital compound, but for us it’s been very helpful. We get a lot of support from the hospital,” says Flugelman, adding that this is partly why the company has been able to bring two products to phase I trials on such limited resources. Since leaving the incubator, the company has raised only $7 million from angel investors in one round.
The company began testing in the lab and later moved on to animals. Phase Ia clinical trials, which test both safety and efficacy, began earlier this year.
Flugelman hopes that around 10 patients will take part in these trials, which are also to take place at the Penn University Medical Center, in Philadelphia. Initially the company will focus on patients with blocked arteries in their legs, but also plan to treat patients with blocked arteries in the heart.
The response from doctors taking part in the trials has been good. “The principal investigators are very pleased with the outcome, but we are all scientists and are trying to control our enthusiasm and wait and see whether things continue to go well,” Flugelman said.
The company is now in the middle of a new financing round and hopes to use the money for expansion and to go through Phase II and III trials. If all goes well, the treatment should reach the market by 2011, and Flugelman, who is still a practicing cardiologist, is already exploring marketing options with large hospitals, biotech firms, and pharma.
In the meantime, the company is continuing R&D on two more products. The first is a biosynthetic graft for bypass surgery using cells from the vein or artery. Currently a bypass graft is made from Teflon, but there is a high failure rate. MGVS’s solution, the MultiGene Graft (MGG), involves covering this bypass graft with the patient’s own cells. “In animals the failure rate was significantly reduced,” says Flugelman.
The company is also using the same technology for grafts used in dialysis. Clinical trials of both these products will start soon. While MGVS’s office remains at the Carmel center, it now plans to hire staff in the US. At present the company employs 40, of which 12 are part time.
“I hope we will reach the market soon and become a global leader in this field,” says Flugelman. “We are moving forward nicely, but it takes time. In the years ahead we will change the way these patients are treated, reduce the number of amputations, and reduce the amount of suffering these patients experience.”