HAVANA — Like many diabetics, Miguel Sobrino suffers from nerve damage that, in turn, inhibits his blood circulation.
A few winters ago, after a small cut on his left foot turned into an ulcer that refused to heal, a condition resulted called “diabetic foot.” With not enough blood reaching his lower extremities, his wound was deprived of the oxygen and nutrients needed to heal.
First, his toes turned black, followed by his foot. Then his ankle began to blacken as gangrene began spreading up his leg. At that point, his doctors scheduled immediate surgery.
“One doctor wanted to amputate to the ankle,” he remembers. “Another to the knee.
"I was in a panic.”
Just days away from surgery, Sobrino sought out one last opinion. “I went to see the physician at my job. And that lucky hunch saved my leg.”
Cutting-edge medical research
It’s even luckier for Sobrino that he doesn’t work just anywhere. The 67-year old gardener tends the sprawling grounds at Havana’s Center for Genetic Engineering and Biotechnology (CIGB), a 754,000 square-foot complex that forms the cutting edge of Cuba’s biotech industry, a priority for the Castro government since 1981.
Marking its 25th anniversary this year, the CIGBhas produced an array of health care products for sale on the global pharmaceutical market including a “clot buster” for heart attack victims and a small yellow pill derived from sugarcane that lowers dangerous cholesterol and lipoproteins. In addition, the center claims to have produced the world’s only meningitis B vaccine.
Some U.S. officials have questioned the industry’s real purpose, alleging that it’s a façade for military research to manufacture biological weapons such as like anthrax and bubonic plague. Cuban scientists dismiss the charges, stating that their work is rooted in finding cures for many diseases.
CIGB’s 1,200 researchers are responsible for the lion’s share of Cuban medical discoveries. Mostly due to their efforts, the country has patents pending on some 150 new medicines and technologies that treat a range of diseases — from heart disease and different cancers to AIDS — and is marketing its products worldwide.
At the time of Sobrino’s crisis, a group of scientists had begun testing a new product they named Citoprot-P. Based on a special protein called human epidermal growth factor, they planned to inject the medicine directly into the foot wound in order to stimulate the scar tissue and heal an ulcer incapable of self-repair.
Sobrino was a perfect candidate for their Phase I testing, according to the scientist behind Citoprot-P, Dr. Jorge Berlanga, who also found 28 other volunteers just days away from amputation. “We took the most challenging patients, willing to risk an untried treatment,” he said.
The first tests, conducted at Havana’s National Institute of Angiology and Cardio Vascular Surgery, concluded with a 50 percent success rate, Berlanga said.
In Sobrino’s case, three injections a day for three weeks stopped the gangrene from spreading and reversed most of the damage in his foot, although he lost his toes. The experimental treatment also eradicated the gangrene that had started in his other foot. Three years later, Sobrino has not had a recurrence.
Berlanga said the study also demonstrated that effectiveness was linked to dosage, a discovery that led to a second phase. “We tested 41 critical patients," said Berlanga. "Everyone had between a 90 percent and 100 percent probability of amputation. With the higher dose, we successfully regenerated the scar tissue in 85 percent of the cases.”
The drug is now in Phase III clinical trials and is being tested on some 100 patients island-wide.
Dr. Pedro Lopez, CIGB’s director of regulation and clinical study, is convinced Berlanga has made a significant discovery. “Even if the average drops to 50 percent success, we’ll still be saving countless lives,” said Lopez, who said he considers himself a cautious man.
In the first two trials, patients taking Citoprot-P experienced few adverse reactions. Some patients ran low-grade fevers and one patient dropped out, said Lopez. “Up to now, the product appears to be safe.”
Citroprot-P also seems to work slightly better in men than women, something being looked at in the next study.
Cubans' work 'very clever'
And, indeed, more studies do need to be done, said Dr. Kelman Cohen, Emeritus Professor of Plastic and Reconstructive Surgery at Virginia Commonwealth University, in Richmond, Va., who last year attended an international symposium in Havana to discuss breakthroughs in wound healing research. It was at the meeting where Cohen learned about the experimental treatment that Berlanga and his team of scientists are using.
Cohen explained that these growth factors are on the market elsewhere and that they are also experimenting with them in India, but that it is how the Cubans are applying them — "in a very novel way" — is where they are making breakthroughs.
“What the Cubans have now done is very clever,” Cohen explained. “Rather than just dumping it into the wound, they’ve injected it into the healthy margins of the wound, thereby allowing it to kick-start the wound healing before it’s destroyed.”
However, while Cohen noted that the Cubans research has so far been very “promising,” he says they need to do some more rigorous research.
“My feeling is that the Cubans, and they know this, need to do carefully controlled double-blind studies, and they are trying to do that,” said Cohen.
But, said Cohen, the political situation between the United States and Cuba is an unfortunate impediment.
“Cuba has some very advanced ideas and we’re not taking advantage of them.”
Other countries, however, are. Lopez says he expects to be selling the drug abroad, especially in the developing world where diabetes rates are growing and amputation is frequent. At the same time, Cuban biotech managers reportedly are in talks with a European pharmaceutical company interested in partnering to conduct clinical trials.
There certainly would seem to be a market — diabetes has become a growing global epidemic, expected to affect 333 million people globally by the year 2025, according to the World Health Organization.
In the U.S., approximately 800,000 new cases of diabetes are diagnosed each year, according to the Centers for Disease Control. Now the seventh leading cause of death in the U.S., diabetes affect almost 21 million Americans. The CDC has also warned that one-third of all children born in the U.S. in 2000 will develop diabetes — some 45 million people by 2050.
According to the CDC, the amputation rate for diabetics is 10 times higher than for non-sufferers. Every year, some 90,000 American diabetics undergo amputations.
Globally, the International Diabetes Foundation found that life expectancy after amputation is diminished and surgery can cost up to $65,000 in the developing world. Citroprot-P costs considerably less, with a full cycle of treatment costing between $18,000 and $28,000 and lasting five to eight weeks.