AWESOME: A diabetes breakthrough from India

[Guynextdoor]

A diabetes breakthrough from India

Read more at: A diabetes breakthrough from India


New Delhi: A team of Indian scientists has discovered a novel form of insulin that could drastically reduce the suffering diabetics face in controlling their blood sugar.

For the diabetics, daily painful pinpricks to inject doses of insulin is a routine affair, now in a new discovery scientists claim a single shot of insulin could help keep sugar levels under control for more than a month. Today the effect of each insulin injection lasts at best for a day.

India is considered the diabetes capital of the world, with as many as 50 million people suffering from this chronic disease, so any new discovery is welcomed with open arms.

The team spent two million rupees and took two years to come with this novel solution. These scientists have already patented the technology, commercialized it and the new insulin could well become a big money spinner in times to come, feels the man who discovered this new form of insulin. (Read - US: Did diabetes drug maker hide test data on risks?)

"It is a multi-million dollar technology transfer agreement with royalties once the product goes to the market and if I am not wrong it is one of the biggest scientific innovations to have come from a government owned research laboratory," said Professor Avadhesha Surolia, Director, National Immunology Institute, New Delhi.

The researchers treated natural human insulin at varying temperatures and chemical conditions and one such special formulation does the magic. In experiments done on rats, mice and rabbits the team could control the sugar levels like of these diabetic rats simply by giving an injection once every three months.

Imagine having to do away with multiple injections everyday to control the sugar problem. The simplicity of the discovery and its huge potential has attracted immediate attention.
"Both conceptually and for clinical practice it is an exciting discovery because it uses natural chemically unchanged insulin and clinically it is useful because it provides ease for patients by reducing the number of pin pricks," said Dr Ambrish Mithal, Diabetologist and president, Endocrine Society of India.

It is not often that new drug is discovered in India, but its use in humans could still be many years away.

 

[gubbi]

A diabetes breakthrough from India

Read more at: A diabetes breakthrough from India


New Delhi: A team of Indian scientists has discovered a novel form of insulin that could drastically reduce the suffering diabetics face in controlling their blood sugar.

For the diabetics, daily painful pinpricks to inject doses of insulin is a routine affair, now in a new discovery scientists claim a single shot of insulin could help keep sugar levels under control for more than a month. Today the effect of each insulin injection lasts at best for a day.

India is considered the diabetes capital of the world, with as many as 50 million people suffering from this chronic disease, so any new discovery is welcomed with open arms.

The team spent two million rupees and took two years to come with this novel solution. These scientists have already patented the technology, commercialized it and the new insulin could well become a big money spinner in times to come, feels the man who discovered this new form of insulin. (Read - US: Did diabetes drug maker hide test data on risks?)

"It is a multi-million dollar technology transfer agreement with royalties once the product goes to the market and if I am not wrong it is one of the biggest scientific innovations to have come from a government owned research laboratory," said Professor Avadhesha Surolia, Director, National Immunology Institute, New Delhi.

The researchers treated natural human insulin at varying temperatures and chemical conditions and one such special formulation does the magic. In experiments done on rats, mice and rabbits the team could control the sugar levels like of these diabetic rats simply by giving an injection once every three months.

Imagine having to do away with multiple injections everyday to control the sugar problem. The simplicity of the discovery and its huge potential has attracted immediate attention.
"Both conceptually and for clinical practice it is an exciting discovery because it uses natural chemically unchanged insulin and clinically it is useful because it provides ease for patients by reducing the number of pin pricks," said Dr Ambrish Mithal, Diabetologist and president, Endocrine Society of India.

It is not often that new drug is discovered in India, but its use in humans could still be many years away.

Ha, Prof. A. Surolia! I worked for him when he was the chief of MBU at IISC!!
A scientist par excellence!! A very knowledgeable man indeed and a very kind human being!! He was the one who encouraged me to apply to US univs for grad studies!

On topic, that seems to be an excellent achievement! Anyone one has more info on the subject?


@ Mods, please move this to the Science sticky. Thanks.

 

[gubbi]

New insulin form may keep sugar low in diabetics for 3 months

Diabetics, who need insulin injections daily, may now hope for some relief with Indian scientists having discovered a novel form of the hormone that can keep blood glucose levels down for upto three months. A team of scientists of the National Immunology Institute of India, led by Mr Avdesh Surolia, has developed a fresh approach to insulin injection wherein 'Supramolecular Insulin Assembly-II (SIA-II)', a form of the hormone, is used for a sustained treatment of diabetes mellitus type-I. The studies constitute the first work of its kind where a single administration of SIA-II to animal models of diabetes, such as rats, has been experimentally demonstrated to lower blood glucose levels to normal values for as many as for 120 days.
SIA-II, which is in the form of a prodrug, when injected releases just above basal levels of insulin into the blood in a sustained manner, Mr Surolia said. A prodrug is a chemical that undergoes changes in the body into a more active material. This just above basal level of insulin is adequate to tackle the increase in blood glucose levels after meals and does not cause severe hypoglycaemia, a low sugar condition, in the morning, a dreadful condition faced by diabetics, he said. According to Surolia, SIA-II upon injection forms a depot at the site, from where insulin monomers are released which act on the body's cells to regulate uptake of glucose for months after a single injection. This is in contrast to the existing treatment method in which the patient needs to inject insulin at least twice a day for maintaining glucose levels. And even then blood glucose still increases between the meals as the insulin injected gets degraded very soon. SIA-II is unique as it is continuously releasing insulin in the body regularly thereby affording a way to curb increases in glucose levels in between meals. The technique is being seen as one with tremendous therapeutic potential and constitutes a new way of treatment for diabetic patients. Experiments carried out by the group in the laboratory have demonstrated that SIA-II acts as a pure and compact source of insulin and that the reason for its long-term bio-availability is its protection from destruction because of its presentation in a compact form. The research may also give a direction for new therapeutic approaches for various diseases. The hormone insulin is the key regulator of energy and glucose metabolism in the body, besides playing a role in development during growing up years. The fine balance of maintaining the required insulin concentrations in the blood is performed by pancreas. At present, diabetes afflicts nearly 200 million people across the world with a large chunk of patients being in India and China. The latest research is an attempt to address the issue of multiple injections.

This should explain what the research group has done. Any questions, and I shall be happy to answer them for you.

 

[Spring Onion]

Gubbi what about those who's sugar level is not so high to take insulin, can they be benefited from this ??

if yes please post details i need it

Thanks

 

[gubbi]

Gubbi what about those who's sugar level is not so high to take insulin, can they be benefited from this ??

if yes please post details i need it

Thanks

Janaji, if one's blood glucose level is NOT high enough to take insulin, they they should NOT take this or any Insulin formulation. Blood glucose levels vary from individual to individual, from day to day, from the time of the day, from meal to meal, from contents of each meal and from a healthy person to a diabetic person.

Based on lab reports of blood glucose levels, a physician will decide whether to prescribe or not to prescribe Insulin injections. If the physician comes to a conclusion, based on all available data, that insulin is not required and can be managed by controlled diet and mild exercise, then he/she will not prescribe Insulin. Theres a very good reason why they will not prescribe.

Giving Insulin to patients whose glucose levels can be managed by other means (exercise and diet) will lead to dangerously low levels of glucose in the blood which can be life threatening or even fatal! Its a very delicate balance of Insulin level and blood glucose levels, especially in Diabetic patients.

But, if the doctor does prescribe Insulin, then, yes, this formulation would revolutionize the field and help tremendously with patient compliance.

Hope that answers your query.

 

[Hutchroy]

Gubbi what about those who's sugar level is not so high to take insulin, can they be benefited from this ??

if yes please post details i need it

Thanks

Auntie Jana,

You can contact Professor Avadhesha Surolia, Director, National Immunology Institute, New Delhi at the following E-Mail Address :

E-Mail: surolia@nii.res.in

 

[Cityboy]

Gubbi what about those who's sugar level is not so high to take insulin, can they be benefited from this ??

if yes please post details i need it

Thanks

well. It is for type 1 diabetes. .not for type2. .

 

[CardSharp]

I'm actually a pharma chem student too and I was curious. From your description this works similar to hormonal birth control implants.


"Implanted Contraceptives

small, flexible rods containing a synthetic hormone; they are implanted under the skin, using a local anaesthetic. These rods release small amounts of hormone from the time implanted, and depending upon when implanted, can be effective 24 hours following insertion. The implanted rods can be effective in preventing pregnancy for up to 5 years. The rods prevent the development and release of a mature egg."

From what I can gather from the patent, SA-III is a compact polymeric form of insulin that slowly degrade (what mechanism?) to amyloid fibrils then to active monomeric insulin. Correct me if I'm wrong

patent link
Compositions For the Treatment of ... - Google Patent Search

 

[gubbi]

I'm actually a pharma chem student too and I was curious. From your description this works similar to hormonal birth control implants.

From what I can gather from the patent, SA-III is a compact polymeric form of insulin that slowly degrade (what mechanism?) to amyloid fibrils then to active monomeric insulin. Correct me if I'm wrong

patent link
Compositions For the Treatment of ... - Google Patent Search

Yes, you are correct. I have searched the patent and it doesnt say anything about the mechanisms involved in degrading the complex polymer into active monomers, unless I might have missed something. (my excuse is - right now I am sleepy, just got back form the lab!)

Its very interesting to note that you have both alpha helices and beta sheets in the polymeric complex of Insulin, and yet when the monomer is released, the two di-sulphide bonds are intact and the molecule reverts to its native conformation and retains its activity. Is there a chemical modification of Insulin which allows the protease resistant polymer to form and to be degraded slowly over a period of time in the tissues? Is there a specific enzyme in the tissue which is responsible for releasing the monomer?

Come to think of it, the processes which can reverse this beta-sheet formation could also, theoretically, be utilized to undo APP amyloid fibrils in AD brains.

Like I said, I am tired for mow, let me know if you find anything in the patent application. I will try to get some info from my friends who also worked for Prof. Surolia.

ps: I too did a Masters in Pharmaceutical Chemistry!! What are you working on? I worked on COX-2 inhibitors (substituted sulphonamide pharmacophore with azide group in known molecules, did both in-silico and synthetic chem)PM me if you want to carry on with this conversation.

 

[CardSharp]

It's hard to say without more info or a timeframe for activity, but the polymeric form probably has a different disulfide bonding arrangement (I can't see stable alpha helixes or beta sheets without different di-s bonds). Once released I'd imagine that the bonds reform into natural state with the help of a GSH and GSSG mediated mechanism.

As for what the release enzyme is... you probably have to look at the specific pka but they did say it was effective over something like a year.

Do you have a crystal structure or know what the the polymer is?

---------- Post added at 02:27 AM ---------- Previous post was at 02:26 AM ----------

Oh I'm just a undergrad right now and I shouldn't say pharma chem, I'm more pure chem but like drugs

 

[gubbi]

It's hard to say without more info or a timeframe for activity, but the polymeric form probably has a different disulfide bonding arrangement (I can't see stable alpha helixes or beta sheets without different di-s bonds). Once released I'd imagine that the bonds reform into natural state with the help of a GSH and GSSG mediated mechanism.

Yes, but then the correct orientation of the second polypeptide wrt the first one through correct SS bonds is absolutely necessary for the molecule to retain activity. What if the orientation changes during release from the polymer? AFAIK that isnt happening. So apparently those SS bonds are probably intact in the polymeric form.

As for what the release enzyme is... you probably have to look at the specific pka but they did say it was effective over something like a year.
Do you have a crystal structure or know what the the polymer is?

Its very difficult, as it is, to crystallize protein molecules in their monomeric form, let alone a polypeptide which is present in a polymeric form. I wish I knew what exactly the polymer in question comprises of. Anyway, this is a relatively new project in Prof. Surolia's lab. I was working on a totally unrelated project - which was THE big project at that time.[/QUOTE]

 

[Wounded Healer]

Great news. Can't wait to see the results of the human trials. India certainly is way ahead in diabetes research.

From a seminar i attended a few months ago, it was said that India was also preparing an Insulin capsule, which will work like an Insulin injection but without the hassle of pricking yourself time and again.

Also i heard that researchers in India were developing a Poly-capsule, meaning that one capsule will contain about six different chemicals, namely, aspirin, statin, clopidogrel, sulfonylurea etc. Any news about that?

regards,

 

[gubbi]

Great news. Can't wait to see the results of the human trials. India certainly is way ahead in diabetes research.

For the Diabetes capital of the world, this still isnt enough!

From a seminar i attended a few months ago, it was said that India was also preparing an Insulin capsule, which will work like an Insulin injection but without the hassle of pricking yourself time and again.

There have been numerous attempts to make an Insulin formulation (medicine packed in the form of tablet or capsule etc) which can be taken orally. The problem is that to be effective, Insulin should be absorbed in the stomach or the small intestine and get into the blood. Insulin is a protein molecule. And once it gets into the stomach, there are enzymes in the stomach (Pepsin) which breaks down the protein molecules into smaller components (amino acids) for better absorption.
You want the intact Insulin molecule to reach blood, not broken down pieces.
Hence Insulin cannot be given by mouth in the form of tablet or capsule or liquid.

Also i heard that researchers in India were developing a Poly-capsule, meaning that one capsule will contain about six different chemicals, namely, aspirin, statin, clopidogrel, sulfonylurea etc. Any news about that?
regards,

I have no idea for now. But there is a possibility that such attempts are being made. It makes sense to mix drugs (unless there are contraindications or corss reactivities or reactions between different drugs) which are given for related disorders into one dose.
From the list it seems that all those first 3 drugs are used for Heart conditions (aspirin - anticoagulant in small doses; statins - lower blood cholesterol; and clopidogrel -antiplatelet, again anticoagulant.) However addition of the last one -sulfonylurea (anti-diabetic) into the above mixture doesnt seem to make sense at first glance.
I will let you know, if I find any info on that.

 

[Wounded Healer]

Gubbi what about those who's sugar level is not so high to take insulin, can they be benefited from this ??

if yes please post details i need it

Thanks

Jana,

There is no benefit of insulin for those whose sugar level is normal, infact, it can be downright dangerous, as it will certainly lead to hypoglycemia, which is a medical emergency and a life-threatening situation. All non-diabetics should stay away from insulin, as the insulin produced by their beta cells in the islet of langerhans of the pancreas is adequate.

regards,

 

[Wounded Healer]

For the Diabetes capital of the world, this still isnt enough!

There have been numerous attempts to make an Insulin formulation (medicine packed in the form of tablet or capsule etc) which can be taken orally. The problem is that to be effective, Insulin should be absorbed in the stomach or the small intestine and get into the blood. Insulin is a protein molecule. And once it gets into the stomach, there are enzymes in the stomach (Pepsin) which breaks down the protein molecules into smaller components (amino acids) for better absorption.
You want the intact Insulin molecule to reach blood, not broken down pieces.
Hence Insulin cannot be given by mouth in the form of tablet or capsule or liquid.

I have no idea for now. But there is a possibility that such attempts are being made. It makes sense to mix drugs (unless there are contraindications or corss reactivities or reactions between different drugs) which are given for related disorders into one dose.
From the list it seems that all those first 3 drugs are used for Heart conditions (aspirin - anticoagulant in small doses; statins - lower blood cholesterol; and clopidogrel -antiplatelet, again anticoagulant.) However addition of the last one -sulfonylurea (anti-diabetic) into the above mixture doesnt seem to make sense at first glance.
I will let you know, if I find any info on that.

Thats just the point. A diabetic patient has to be on multiple drugs, namely, a couple of anti-diabetic drugs, aspirin, sometimes clopidogrel if their is any heart condition, statin as diabetes is also associated with metabolic syndrome, a renal protection drug such as ACE Inhibitor or ARBs. From what i heard, the process was underway to combine all these in a single capsule.

The lecture i attended was given by Dr. Riaz Malik, who is a world-renowned Diabetologist and Endocrinologist from the U.K.

A poly-capsule would be of great benefit to the diabetic patients.

regards,