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http://www.livemint.com/2010/07/12235223/NII-scientists-develop-ultra-l.html
Researchers say the 'prodrug' can maintain near-normal blood glucose level in animals for as long as 120 days
Bangalore: In the almost 90 years that insulin has been used for treating diabetes, scientists and businesses alike have strived for its long-lasting analogue that could control blood sugar, relieving the patient from frequent pricks. But the longest that the prevailing insulin types last in the body is 16-18 hours.
In a development that could significantly extend the life of insulin in the body, a team of researchers at the National Institute of Immunology (NII) in Delhi has demonstrated a new "prodrug"—precursor of a drug—that releases just about the right amount of insulin in the body in a sustained manner. Reporting in this week's Proceedings of the National Academy of Sciences, director of NII, Avadhesha Surolia, and his team show that by using this prodrug, which they call supramolecular insulin assembly-II (SIA-II), in various animal models, near-normal blood glucose level is maintained for as long as 120 days.
"This is an extremely exciting piece of work," said Nikhil Tandon, endocrinologist at the All India Institute of Medical Sciences in New Delhi. The gradual release of SIA-II leads to good sugar control in fasting as well as fed state, he added. "Hopefully after completion of the requisite large animal studies, it should be available for testing in humans also."
For researchers, it's promising as there's no chemical modification of the human or bovine insulin used in the prodrug, nor is there any device or patch used.
Surolia has licensed the technology to Life Science Pharmaceuticals (LSP) in Connecticut, US, in an agreement that he claims "to be one of the biggest licensing deals from any academic institution in India".
"We will demonstrate our technology to LSP in the next three weeks, following which its subsidiary, Extended Delivery Pharmaceuticals, will undertake further trials," said Surolia.
Using his lab's extensive work on protein folding, a physical assembly process that is linked to several diseases, but remains an unsolved problem in biology, Surolia and his team "misfolded", or packaged, the existing genetically engineered human as well as bovine insulin in a manner that provided protection from the enzymatic action in the body. In the new form, the insulin, when injected in the body, sits like a depot with millions of molecules which get released for weeks or, as shown in animals such as rats, mice and rabbits, for months.
The challenge now lies in replicating this success in humans.
"Personally speaking, SIA-II can straight away go to human trials. It is pretty safe as we have not modified the insulin, nor is any additive used," said Surolia. Moreover, say Tandon and Surolia, there are no signs of side effects, including cancerous growth.
Experts argue that the excellent blood sugar control achieved in the studies suggests that it's not only basal insulin, or SIA-II, that has done the trick, but there's some recovery of beta cells—insulin producing cells in the pancreas. And if that's the case, then the insulin will not be as long acting in humans with type I diabetes as seen in the animals, argues Steven Russell of the diabetes centre at Massachusetts General Hospital, in Boston, US. "Nonetheless, it is a very long-acting insulin—far beyond what is commercially available."
But the desired period of sugar control in humans, says Surolia, is certainly not several weeks. "We will first test if it works as once in 10 days injection and then extend it to once a month." Even if it lasts for 10 days, it would mean it's 30 times more beneficial, given that in most cases people inject insulin thrice daily.
Russell, on the contrary, thinks "an ultra long-acting insulin such as this is much more likely to be used for type II diabetes where often only basal insulin is needed, than in type I diabetes".
"That suggestion is also welcome," say researchers given that India will have 50.8 million diabetics, mostly type II, by the year end. According to International Diabetes Federation, the poorest diabetics in India spend an average of 25% of their family income on private care. "Our motivation was to reduce the burden of diabetes, doesn't matter whether it's type I or II," said Surolia.
Researchers say the 'prodrug' can maintain near-normal blood glucose level in animals for as long as 120 days
Bangalore: In the almost 90 years that insulin has been used for treating diabetes, scientists and businesses alike have strived for its long-lasting analogue that could control blood sugar, relieving the patient from frequent pricks. But the longest that the prevailing insulin types last in the body is 16-18 hours.
In a development that could significantly extend the life of insulin in the body, a team of researchers at the National Institute of Immunology (NII) in Delhi has demonstrated a new "prodrug"—precursor of a drug—that releases just about the right amount of insulin in the body in a sustained manner. Reporting in this week's Proceedings of the National Academy of Sciences, director of NII, Avadhesha Surolia, and his team show that by using this prodrug, which they call supramolecular insulin assembly-II (SIA-II), in various animal models, near-normal blood glucose level is maintained for as long as 120 days.
"This is an extremely exciting piece of work," said Nikhil Tandon, endocrinologist at the All India Institute of Medical Sciences in New Delhi. The gradual release of SIA-II leads to good sugar control in fasting as well as fed state, he added. "Hopefully after completion of the requisite large animal studies, it should be available for testing in humans also."
For researchers, it's promising as there's no chemical modification of the human or bovine insulin used in the prodrug, nor is there any device or patch used.
Surolia has licensed the technology to Life Science Pharmaceuticals (LSP) in Connecticut, US, in an agreement that he claims "to be one of the biggest licensing deals from any academic institution in India".
"We will demonstrate our technology to LSP in the next three weeks, following which its subsidiary, Extended Delivery Pharmaceuticals, will undertake further trials," said Surolia.
Using his lab's extensive work on protein folding, a physical assembly process that is linked to several diseases, but remains an unsolved problem in biology, Surolia and his team "misfolded", or packaged, the existing genetically engineered human as well as bovine insulin in a manner that provided protection from the enzymatic action in the body. In the new form, the insulin, when injected in the body, sits like a depot with millions of molecules which get released for weeks or, as shown in animals such as rats, mice and rabbits, for months.
The challenge now lies in replicating this success in humans.
"Personally speaking, SIA-II can straight away go to human trials. It is pretty safe as we have not modified the insulin, nor is any additive used," said Surolia. Moreover, say Tandon and Surolia, there are no signs of side effects, including cancerous growth.
Experts argue that the excellent blood sugar control achieved in the studies suggests that it's not only basal insulin, or SIA-II, that has done the trick, but there's some recovery of beta cells—insulin producing cells in the pancreas. And if that's the case, then the insulin will not be as long acting in humans with type I diabetes as seen in the animals, argues Steven Russell of the diabetes centre at Massachusetts General Hospital, in Boston, US. "Nonetheless, it is a very long-acting insulin—far beyond what is commercially available."
But the desired period of sugar control in humans, says Surolia, is certainly not several weeks. "We will first test if it works as once in 10 days injection and then extend it to once a month." Even if it lasts for 10 days, it would mean it's 30 times more beneficial, given that in most cases people inject insulin thrice daily.
Russell, on the contrary, thinks "an ultra long-acting insulin such as this is much more likely to be used for type II diabetes where often only basal insulin is needed, than in type I diabetes".
"That suggestion is also welcome," say researchers given that India will have 50.8 million diabetics, mostly type II, by the year end. According to International Diabetes Federation, the poorest diabetics in India spend an average of 25% of their family income on private care. "Our motivation was to reduce the burden of diabetes, doesn't matter whether it's type I or II," said Surolia.
