Alpha 1 Antitripsin Update from Dr. Eli Lewis
A couple of years ago, Dr. Lewis was kind enough to share his initial work with us on Alpha 1 Antitrypsin and islet cell therapy. In a nutshell, AAT would allow transplantation of islet cells without the use of immunosuppressant drugs.
This is a big deal, because often immunosuppressant drugs are as hard on the body as the disease itself. AAT is a naturally occurring anti inflammatory that the body makes, but when disease enters the body often AAT is depleted. AAT is most often used in treating emphysema patients, but now there is the potential to use it in diabetes.
Please read Dr. Lewis’s earlier post here.
Now Dr. Lewis’s update on AAT is broader than I expected. More areas of research are focused on ATT and the results are interesting and exciting! Here is his update:
From Dr. Lewis and the Clinical Islet Laboratory for the Study of Immunology, Transplantation, Inflammation and Diabetes at Ben-Gurion University of the Negev:
Diabetes and more diabetes: We keep on saving pancreatic islets! The most profound outcome is the clinical trial for kids with type 1 diabetes that was completed in Israel. Still under analysis, the first results show excellent unprecedented safety in kids above 4 years old, and reversal of diabetes in the individuals that started therapy earliest. Some parameters have never been met in other trials and have the endocrinologists puzzled. Why 'more' diabetes? Because we finally entered some aspects of type 2 diabetes: we have concrete evidence that our approach benefits in the case of obesity and insulin resistance, and a publication that came from another group lends yet more support to this.
For example, we now are able to block the death of islets that occurs when fatty acids are high in the blood. Still, there's more diabetes: Islets are known to expire by way of drug-toxicity, some drugs as common as immunosuppressants and also psychiatric drugs.
We've now proven that islets survive these medications in perfect condition; the current approach in medicine is -- none! Just let the patients know that they're risking diabetes by taking these drugs (a 20% chance of leaving the hospital with newly acquired drug-induced diabetes). So it's wonderful news all around for islets. In the meanwhile, we're gaining critical knowledge regarding the mechanism of our molecule, but that's the basic science part, less clinical. Running these projects are Galit (tech), Noa (Ph.D.), Nofar (M.Sc.) which send their regards.
Transplants on the verge of a breakthrough: We actually started with transplants 6 years ago and were drawn by the immunology into diabetes. Meanwhile, some of the elements that we uncovered in our studies were pursued in depth and have now just been accepted for publication: We found a way to allow complex transplants from two species to safely function despite the immune system! This will apply to, for example, pig-to-human transplants. We've set the approach in a patent to protect BGU once the pharma industry realize they can use the approach. Again, as in diabetes, we're gaining incredible insight into many processes, but the arrowhead is still clinical; the approach is absolutely safe. The project is run by Boris (Ph.D.) who sends his regards from the army reserve these days.
Bacterial infections provide a pleasant surprise: We sought out to rule out a simple concern: are animals susceptible to infection when we apply our approach? We were stunned to discover that they're in fact even more protected. The mechanism is a topic of enormous interest. Indeed, the president of the Israeli Society for Microbiology approached us flabbergasted by the results that we shared in a conference, and we're now collaborating.
We were also invited to Germany to present our work to a European consortium on bacteria. The 'big deal' is that this is not an antibiotic effect. Mixed together with germ, our drug does nothing. But have a tissue immersed in it, and bacteria don't adhere. Since it's safe, we're now exploring an ointment-preparation, as well as an acute lung infection model and an abdominal infection model. In all – the drug we examine affords a dramatic decline in bacterial burden. Imagine an elderly patient in the hospital, and the opportunity to introduce the drug by inhalation so as to prevent bacteria colonization during his stay. Being that the bacteria are not the direct target in this case, it is anticipated that bacterial resistance will find it hard to emerge. This is Ziv's work, a Ph.D. who joined us from the industry. The ointment, by the way, is the work of Ronen, M.Sc., who came from pharmacology and brought with him outstanding aspects of our therapeutic approach. He sends regards from Thailand, traveling with his wife before they both become engulfed in the work planned ahead.
An unexpected finding to do with cancer: I know we're supposed to study diabetes, but we again had to exclude a major concern: when one tampers with the immune system, one must consider the possibility that cancer cells will enjoy this window of opportunity. So we set to examine this and were again blown away – we stuck cancer cells in specific areas in animals, as the standard protocol reads, and instead of the tumors increasing in size as the control group had, the mice treated by our approach had no visible tumor growth! Now this seems like science fiction but we actually know what stands behind the outcome. As it turns out, the drug we applied turns parts of the immune system off, allowing transplants to survive and allowing islets to sustain immune responses.
Yet, the cells that are in charge of killing cancer cells are intact, even enhanced by the drug! This work is Ofer's study (PhD) and we're applying for a UK grant in this field, keep your fingers crossed for a positive response. Ofer came from a lab that studied cancer and this work is his excellent way of combining basic science with our main interest – clinical benefit.
I know this seems vast, but this is how the lab's working these days: six PhDs, five MScs, two techs and a couple of MD students are all invested in exploiting the most of what we know and do best – get immunology working for the better of the patients.
We wish Dr. Lewis and team all the best, and keep up the good work!
More from Dr. Lewis: An Anti-Inflammatory Approach to Type 1 and Type 2 Diabetes