Healthy adult donor chosen; informed consent taken; donor screened

Donor’s bone marrow harvested for stem cells

Stem cells grown in lab. Master cells stored. Intramuscular injection ampoule prepared.

Patient identified; informed consent taken; patient injected

Just walking a few steps is a huge struggle for 41-year-old Sanjay Mondal, a grocer from Nabagram, a village near Behrampore, 200km from Calcutta. “The pain in the legs is excruciating even when I’m not moving. And these sores refuse to heal despite all the medicines,” says Mondal with a grimace, as he shows his bluish feet, freckled with sores.

“He’s suffering from Buerger’s disease, a disorder in which blood vessels of the hands and feet get blocked,” says Santanu Dutta, cardiovascular specialist at SSKM Hospital in Calcutta. “The condition is called critical limb ischaemia (CLI). It has no cure and the goal is to control symptoms. It often needs amputation if there is widespread tissue death (gangrene).” That was evident from Mondal’s three missing digits. According to Dutta, most doctors fail to diagnose the disease in time. So there’s little else to be done other than amputation.

Now, however, there may be a ray of hope for hundreds of thousands of patients like Mondal. Stempeutics, a Bangalore-based biotechnology company, has been conducting clinical trials with a stem cell based medicine called Stempeucel for CLI. The trials are being held across 11 hospitals in India, including three in Calcutta — Nightingale Hospital, Calcutta Medical College and Health Point Hospital. “Mondal is expected to get the therapy in a week or so,” says Dutta.

It’s too early to divulge the details but the outcome is quite satisfactory, says Anjan Das, director, clinical research, Stempeutics. “Sores have healed and patients are walking on their own,” adds Dutta.

The clinical trials are going through Phase II, which checks whether the treatment works. “Patients are being treated with proprietary product Stempeucel, a preparation of mesenchymal stem cells which are harvested from the bone marrow of healthy adult donors,” says Das. “Unlike most other types of adult stem cells, mesenchymal cells grow well in the lab, so thousands of doses can be produced from a single donation,” he adds. These progenitor cells are expected to stimulate resident stem cells and regenerate the damaged tissue. Since the cells are derived from adults, they do not raise the ethical concerns of embryonic stem cells, whose creation usually involves the destruction of human embryos. “These cells are being injected in the calf muscles and also around the ulcer,” says Pawan Gupta, director, medical services, Stempeutics.

“I am not aware of the status of the trial but this is one of the few officially-approved stem cell trials,” says Polani B. Seshagiri, a member of the government panel that recommended to the Drug-Controller General of India (DCGI) that Stempeutics be permitted to hold this trial. Says Geeta Jotwani, assistant director general, Indian Council of Medical Research (ICMR), “We have received reports of the trials. The company has sought approvals for the next phase of trials which is under consideration.” ICMR sets ethical guidelines for human trials of any new drug in the country.

While the clinical trials of many stem cell drugs are being held in India, most are being held clandestinely, without following proper process and procedure. This has prompted criticism that local regulators were failing to monitor the procedures. The due process of the Stempeutics clinical trial is robust and transparent, and may become a benchmark for future such trials. Seshagiri, who heads the Stem Cell and Transgenic Research Lab at the Indian Institute of Science in Bangalore, says, “These trials are following all protocols laid down by the law of the land and the procedure is well documented.”

Apart from CLI, stempeucels are undergoing trials for osteoarthritis and alcoholic liver diseases. The company is also in the process of devising stem cell-based therapies for diseases like diabetes and heart blocks. Stempeutics, however, is not the only company working on stem cell-based therapy. Mumbai-based Reliance Life Sciences is yet another company that has got government approval for clinical trials with stem cells for vitiligo, diabetics ulcers and so on. Relinetra, a stem cell-based medicine for corneal blindness has already been launched in the market.

Globally, US-based Osiris Therapeutics, Australian firm Mesoblast and the Israeli firm Gamida Cell are surging ahead with clinical trials with mesenchymal stem cell-based therapies.

The therapies are promising but experts believe these are still going through a trial-and-error phase. Says Seshagiri, “There’s a long way to go and it is too early to accurately predict the final outcome. Getting to know the exact dose of stem cells for a particular patient and determination of the best time to offer the therapy will take some time.” Stempeutics, however, is planning to go for the third and final phase of trials after the current phase covers an adequate number of patients. “We hope to launch stempeucels for CLI therapy in the market by 2015,” says Gupta.

SSKM’s Dutta is eagerly waiting for that day when he will be able to see patients like Mondal walk home. “If stempeucel works for CLI, it will pave the way to several other critical cardiovascular problems.” If it can heal leg muscles damaged by lack of blood, there is no reason it cannot be used to treat cardiac muscles damaged because of a blocked artery. And that can revolutionise cardiac medicine.

Let’s wait with our fingers crossed.