Lung Disease Drug May Stop Progression of Type 1 Diabetes


A drug recently approved by the FDA for the treatment of adults with certain congenital respiratory diseases, may delay the progression of type 1 diabetes.

Glassia®, the flagship product of the Israeli biopharmaceutical company, Kamada, was developed to treat Alpha-1 antitrypsin (AAT) deficiency, a hereditary condition characterized by a low level of alpha-1 protein in the blood and the lungs.

So, what does a drug to treat lung disease have to do with type 1 diabetes?  What’s the connection?  To find out more we talked to Yaron Cherny, Kamada’s director of business development, about this exciting new drug and the promise it holds for the treatment of type 1 diabetes.

 Please tell us about Alpha-1 Antitrypsin? What is it?

 AAT is a naturay occurring protein, produced by the liver, which helps protect lung tissue from damaging enzymes that are released by white blood cells.  A lack of AAT may result in early onset emphysema and severe lung damage.  Some people have a liver that does not produce the protein at all or produces an inactive protein.

 AAT is known for its anti inflammatory activity together with its ability to protect the cell tissue. In addition, AAT in the lungs balances the activity of a different protein, neutrophil elastase, and in doing so protects the lungs from protease-mediated tissue destruction which sometimes leads to emphysema.

What can you tell us about Glassia®?

Yaron ChernyGlassia® is Kamada’s intravenously administered AAT replacement therapy for patients suffering from AAT deficiency. It was approved by the U.S. FDA  in 2010 and soon after the company entered a strategic exclusive distribution agreement for Glassia® in the U.S. with Baxter. Kamada has been marketing the AAT IV product since 2005 in Israel, Brazil and other countries.

 An inhaled version AAT replacement therapy is already in advanced stages of a pivotal phase 2-3 clinical trial in the EU for the treatment of AAT deficiency.

 Kamada also conducted a phase 2 trial to treat cystic fibrosis patients and another phase 2 trial to treat bronchieactasis.  We’ve published excellent safety results and indication for efficacy.

 Recently we announced the initiation of a phase 1-2 proof of concept clinical trial to treat type 1 diabetes.

 How did this come about?  In other words, how did you get from lung disease to type 1 diabetes? 

In recent years, there have been several studies conducted with Glassia® that support the idea of treating diabetes with AAT. These studies showed that AAT stops the inflammatory process, can delay the progression of the disease and stop the destruction of the insulin producing beta cells.

Several studies with diabetic animals have shown that in the presence of AAT, the animal recovers, and that diabetic animals treated with AAT in due time did not develop the disease.

Experiments done with AAT, including Glassia®, have also shown preliminary safety and efficacy.

Whose idea was it to test AAT as a diabetes treatment?

The scientific idea behind the trial is to use the anti inflammatory activity of AAT, and by that stop the inflammation of the pancreas.  The anti inflammatory properties of AAT are very well known in the research world and Kamada  decided to take the leap and bring it to clinical trial in patients with type 1 diabetes who are in their honeymoon period (newly diagnosed).

Type 1 diabetics do not suffer from AAT deficiency so why would AAT replacement therapy benefit them?

Recent studies have shown that patients with type 1 diabetes may not be AAT deficient and may have normal levels of AAT but the protein in type 1s is not as active as in healthy non-diabetics.

How would this therapy be used with type 1 diabetes patients? Would it replace insulin therapy?

We don’t have enough data to answer this question. The drug is aimed at preventing and or decreasing damage to beta cells which produce insulin. So, if the drug works, it might replace insulin fully or partially.  But we still don’t know if it will, or at what stage of disease, or for how long. The drug does not perform the same function insulin does. The drug is targeted at saving the cells that produce insulin.

 Who would be a candidate for AAT replacement therapy? (Your inclusion criteria is within 6 months of diagnosis with some insulin production.)

The main inclusion criteria is early diagnosis of type 1 diabetes.  See at for more inclusion/ exclusion criteria.

 AAT has been demonstrated to have protective effects on islets when included directly in islet media; is there any evidence that exogenous AAT has tissue-specific protective effects in vivo? In other words, is there any evidence that circulating AAT will have a measurable effect on islet cells, rather than just overall inflammation?

 Yes, there is evidence that AAT has protective effect on islets in various systems, including in vivo studies. For example, we have seen the protective effects both during transplantation of islets and during the progression of diabetes in the non-obese diabetic (NOD) mice. *A list of references will appear at the end of this interview.

 A number of trials in recent-onset patients aiming to reduce inflammation and extend beta-cell life have come up short of their primary endpoints, and some argue that the trials need to be started sooner, in at-risk, non-diabetic patients. Do you think relative disease progression is an issue with the AAT trials? Is recent-onset soon enough to see an effect?

Yes, it is assumed at this stage in development that the beneficial effect would be in early stages of disease.

 Would the therapy be injected or inhaled, daily/weekly?  What kind of side-effects do you anticipate?  

 We are starting the first trial. The final/actual dose given in therapy is subject to clinical development. This is not known yet.  The side effects anticipated are the same as listed in the product insert for AAT augmentation therapy in congenital emphysema.

 How long do you anticipate the trials will last?  If all goes well, when might the drug be approved for treating type 1 diabetes?

 Kamada announced that it is expecting to release an interim and final report during 2012.  Please remember – this is only phase 1-2, so it will take some time before we would be able to estimate when the drug would be in the market.  But we’re hopeful.

Karmel Allison and Jessica Apple contributed to this interview.

Michael Aviad is co-founder of ASweetLife.  He writes the blog, Diabetes, It’s An Endurance Sport.



 Lewis EC, Mizrahi M, Toledano M, Defelice N, Wright JL, Churg A, et al. alpha1-Antitrypsin monotherapy induces immune tolerance during islet allograft transplantation in mice. Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16236-41 Epub 2008 Oct 13.

Weir GC, Koulamnda M. Control of inflammation with alpha1-antitrypsin: a potential treatment for islet transplantation and new-onset type 1 diabetes. Curr Diab Rep. 2009 Apr;9(2):100-2.

Koulmanda M, Bhasin M, Hoffman L, Fan Z, Qipo A, Shi H, et al. Curative and beta cell regenerative effects of alpha1-antitrypsin treatment in autoimmune diabetic NOD mice. Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16242-7 Epub 2008 Oct 13.

Strom TB. Saving islets from allograft rejection. Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12651-2 Epub 2005 Aug 29.

Lewis EC, Shapiro L, Bowers OJ, Dinarello CA. Alpha1-antitrypsin monotherapy prolongs islet allograft survival in mice. Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12153-8 Epub 2005 Aug 10.

Kalis M, Kumar R, Janciauskiene S, Salehi A, Cilio CM. alpha 1-antitrypsin enhances insulin secretion and prevents cytokine-mediated apoptosis in pancreatic beta-cells. Islets. 2010 May-Jun;2(3):185-9.

Zhang B, Lu Y, Campbell-Thompson M, Spencer T, Wasserfall C, Atkinson M, et al. Alpha1-antitrypsin protects beta-cells from apoptosis. Diabetes. 2007 May;56(5):1316-23 Epub 2007 Mar 14.

Petrache I, Fijalkowska I, Zhen L, Medler TR, Brown E, Cruz P, et al. A novel antiapoptotic role for alpha1-antitrypsin in the prevention of pulmonary emphysema. Am J Respir Crit Care Med. 2006 Jun 1;173(11):1222-8.

Petrache I, Fijalkowska I, Medler TR, Skirball J, Cruz P, Zhen L, et al. alpha-1 antitrypsin inhibits caspase-3 activity, preventing lung endothelial cell apoptosis. Am J Pathol. 2006 Oct;169(4):1155-66.

Demedts IK, Demoor T, Bracke KR, Joos GF, Brusselle GG. Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema. Respir Res. 2006 Mar 30;7:53.

Loganathan G, Dawra RK, Pugazhenthi S, Wiseman AC, Sanders MA, Saluja AK, et al. Culture of impure human islet fractions in the presence of alpha-1 antitrypsin prevents insulin cleavage and improves islet recovery. Transplant.  2010 Jul-Aug;42(6):2055-7.


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Bernard Farrell
10 years ago

I’m with you on the cure Michael.
I’m fairly sure her initial research on mice used something other than BCG to stimulate TNF production (I misspoke earlier). Whatever she used was toxic to people and so she’s switched to BCG which has been used for decades in various ways. I got some BCG injections as a kid in Ireland for a TB vaccination, and I know that it’s used today as an immunotherapy for folks with bladder cancer.

Catherine Price
10 years ago

Hi Bernard, I am no expert but from what I’ve read she doesn’t inject TFN but the TB vaccine BCG, known formally as bacillus Calmette-Guerin, which stimulated the production of TNF, that killed the cells that were attacking the pancreas.

I read about it in the LA Times and really have a very limited understanding of the subject. 
In any case I would take any one of the “diabetes cures”. 

Bernard Farrell
11 years ago

Thanks Michael. The reason I ask about it’s comparison to TNF is that Dr. Faustman’s research used TNF in mice to knock out white blood cells that she believes are responsible for killing pancreatic cells. Her research showed two defective pathways in mice and the treatment she used seemed to fix that.
I’m not a biology scientist, but it sounds like AAT may have some effect even on people with long-term diabetes. However verifying that would involve an additional set of (expensive) clinical trials. I’ll watch this space.

Catherine Price
11 years ago

@Bernard: I had to ask the people at Kamada about your comment since I do not know anything about TNF. Dr. Eli Lewis, scientific advisor for Kamada, says:  “TNFalpha is an inflammatory agent, and AAT blocks its activity. The antibodies in clinical trials block TNFalpha as well, however, they are specific to TNFalpha and don’t block any other mediator in the attack on islets. Therefore AAT is wider and more effective. More importantly, AAT does not have the side-effects and risks of blocking TNFalpha, especially in long-term experiments; in fact it’s protective in the very same cases. Therefore, AAT is superior in… Read more »

11 years ago

Could AAT be used as a treatment for type 2 diabetes?  And what about for rheumatoid arthritis?

Catherine Price
11 years ago

@Zach – Fixed, thanks.

Catherine Price
11 years ago

@Stoyan – From what I understand the drug is not expected to restore pancreatic cells but only stop the progression of the disease. Therefore the earlier you start the better. The inclusion criteria for the study is 6 months from diagnoses.

11 years ago

Certainly some interesting information – it’s curious to see the different sources people are using to investigate potential treatments/cures to diabetes. As can be expected in such an early stage though, many things remain vague. Can it only be used to stop the progression of diabetes, or can it also potentially restore pancreatic cells? How early in the process must it be applied?
Right now it seems far away from the potential cure category.

11 years ago

(should be

Bernard Farrell
11 years ago

I’m curious about what may happen if you already have type 1 diabetes and are given this disease for lung damage. I’ll bet there are many folks with T1 and asthma-related lung damage (I’m one), any testing to see what might happen there? Does AAT behave in any way similar to TNF (Tumor necrosis factor)?

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