{"id":45252,"date":"2016-11-22T10:17:49","date_gmt":"2016-11-22T15:17:49","guid":{"rendered":"https:\/\/asweetlife.org\/?p=45252"},"modified":"2016-11-23T03:29:37","modified_gmt":"2016-11-23T08:29:37","slug":"nanoparticles-may-be-used-to-treat-type-1-diabetes","status":"publish","type":"post","link":"https:\/\/asweetlife.org\/?p=45252","title":{"rendered":"Nanoparticles May Be Used to Treat Type 1 Diabetes"},"content":{"rendered":"

A couple of weeks ago I sat down with Dr. Francisco Quintana, who runs a lab at Brigham and Women\u2019s Hospital in Boston focused on finding new treatments for autoimmune diseases. In particular, he\u2019s working on developing nanoparticles that would address the autoimmune attack on islet cells that characterizes type 1 diabetes. JDRF has been funding Dr. Quintana\u2019s work in the lab since 2011, and in September it joined with Pfizer and a venture capital firm to fund a biotech start-up called AnTolRx, which will seek to bring targeted nanoparticle tolerance therapeutics (TNTT) to market, to treat type 1 diabetes and a range of other auto-immune disorders. According to Dr. Peter Lomedico, JDRF\u2019s director of research business development, this venture is the first time that JDRF has invested in an academic project and then in a company designed to bring that project to market.<\/p>\n

\"Francisco<\/a>
Francisco Quintana, Ph D<\/figcaption><\/figure>\n

Quintana\u2019s is one of several different immune therapies that JDRF is supporting, partly because JDRF sees a critical gap in the therapies now available for type 1 diabetes. (\u201cYou need multiple shots on goal,\u201d says Lomedico. \u201cIt\u2019s hard to predict what\u2019s going to work.) For other autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, therapies have been developed that slow the auto-immune process. But for type 1 diabetes, Lomedico points out, \u201cwe have no disease-modifying therapy.\u201d In other words, there\u2019s no way to stop the body\u2019s attack on its own beta cells.<\/p>\n

This is an essential line of research for JDRF, for a couple of reasons. It\u2019s now possible to test people for auto-antibodies that show whether or not they are on the way to developing type 1<\/a>. But it\u2019s hard to see the point of doing the test when there\u2019s still no therapy that would stave off the full-blown disease. \u201cWe have a lot of people at risk,\u201d says Lomedico. \u201cAnd we\u2019re waiting for them to become insulin dependent. Some of those people we\u2019re waiting until they\u2019re in DKA because there\u2019s nothing available. We have to do something.\u201d<\/p>\n

That\u2019s where Quintana\u2019s nanoparticles or another immune therapy would come in. And stopping the autoimmune process would be important for those who have already been diagnosed with type 1 diabetes as well. Many people who have been recently diagnosed maintain some beta cell function (thus the honeymoon period that many patients experience after they\u2019ve first been put on insulin therapy). Stopping the autoimmune attack would help them preserve that function for longer, \u201cwhich correlates with better glycemic control and better clinical outcomes,\u201d explains Lomenico. \u201cThis is what we\u2019re trying to get companies to understand. They can make a difference in people\u2019s lives, and it\u2019s a commercial opportunity for companies themselves.\u201d For those who have had type 1 for longer, who may have very few beta cells left, a therapy that solves the autoimmune piece of the puzzle could potentially be used alongside a new source of beta cells, such as what ViaCyte and Doug Melton\u2019s Semma Therapeutics<\/a>\u00a0are working to develop.<\/p>\n

Quintana and I spoke on November 1 in his office at the Ann Romney Center for Neurologic Diseases.<\/p>\n

 <\/p>\n

Could you tell me about the nanoparticles you\u2019ve created and what they do?<\/strong><\/em><\/p>\n

Basically what they do is they reeducate the immune system. As you know, in type 1 diabetes you have a deregulated response of the immune system against the insulin-producing cells; it starts killing them. So what we tried to do with our nanoparticles is to reeducate the immune response\u2014to reprogram it, to reboot it\u2014so it stops attacking the insulin-producing cells. But we have to reeducate it in a very specific manner, because we still need the immune response to be able to fight the microbes we\u2019re exposed to.<\/p>\n

 <\/p>\n

My understanding is that you would add two components to the nanoparticles to combat the immune system\u2019s destruction of the beta cells.<\/strong><\/em><\/p>\n

Exactly. So what the nanoparticles do, as part of this job to reeducate the immune system, is to deliver two signals, or two pieces of information. One of those pieces confers specificity; it\u2019s an identifier of insulin-producing cells.<\/p>\n

The second piece of information is basically a switch off, telling the immune system not to attack this specific set of cells. We want the immune system to learn to tolerate, or relearn to tolerate, the insulin-producing cells.<\/p>\n

 <\/p>\n

If you were to use these in people with T1D, wouldn\u2019t you need a new source of beta cells? It wouldn\u2019t be enough to just turn off the immune attack, right?<\/strong><\/em><\/p>\n

Well, if you intervene early enough you could still be left with enough beta cells to produce physiologically relevant amounts of insulin, and also probably to regenerate beta cells. If you intervene later, you would need to reintroduce insulin-producing cells. But we are only focused on the immune side of the problem.<\/p>\n

 <\/p>\n

Which is a big part of the problem. So you\u2019ve tested the nanoparticles on mice with a form of T1D, and what happened?<\/strong><\/em><\/p>\n

Basically we were able to arrest the disease, even when we treated mice late in their disease process. We were also able to show that if we took T cells from type 1 diabetes patients, we could shut them off or reeducate them.<\/p>\n

 <\/p>\n

So you did that in the lab?<\/strong><\/em><\/p>\n

Exactly. We didn\u2019t do it in humans. And now, and this is something that was published last week<\/a>, we have started to work with humanized mice\u2014mice that have at least some aspects of the immune response. We were able to show that this anti-inflammatory part of our nanoparticles also works in these human T cells in vivo [in a living organism]. It\u2019s a way of getting it closer to the human immune system to show how relevant it is.<\/p>\n

 <\/p>\n

I know there have been a lot of potential type 1 diabetes treatments that have worked in mice but haven\u2019t worked in people. Presumably you\u2019re optimistic about this. What makes you optimistic?<\/strong><\/em><\/p>\n

I think it has to do with the fact that you are not giving only one signal but two. And that you have this tolerance-inducing or tolerogenic signal that seems to be pretty strong. A couple of weeks ago it was reported that the way these tolerogenic signals work is by activating a protein that is called AhR. This is a protein that we\u2019ve been working with for years; we are world leaders in this protein and how it controls immune response, and it\u2019s the same protein we are activating with our nanoparticles. That gives me even more confidence, besides the experiments we are doing with mice.<\/p>\n

 <\/p>\n

When you talk about nanoparticles, as a non-scientist it\u2019s really hard to picture how you work with them, how you create them. <\/strong><\/em><\/p>\n

You can think about the way we make them as chemical reactions. We start with\u2014and this is something unique about ours\u2014colloidal gold, small particles of gold in suspension. The reason we started with this is that for almost 50 years colloidal gold has been used as an anti-inflammatory over the counter, so it has already been used in humans. So we take this gold particle, about 60 nanometers in size [for scale, one meter is a billion nanometers], then through chemical reactions we bind the two pieces to it, then we cover that with a specific layer to increase the stability and the circulation. It\u2019s all done in test tubes. I have specific incubation procedures, dictating the temperature, the agitation, and other variables.<\/p>\n

 <\/p>\n

Are nanoparticles being used to treat diseases now, at this point?<\/strong><\/em><\/p>\n

Not at this point, but there are treatments for several autoimmune diseases that are being developed based on nanoparticles. Ours is a modular system, so it\u2019s very easy to adapt it to other diseases. And indeed, we first developed these nanoparticles using models of multiple sclerosis.<\/p>\n

 <\/p>\n

Are you now farther ahead in type 1 diabetes than MS, in terms of nanoparticles? If so, why are you approaching it from that direction?<\/strong><\/em><\/p>\n

We have several therapies for MS; they don\u2019t cure the disease, but they significantly improve quality of life. We don\u2019t have the equivalent for type 1 diabetes. Then on top of that JDRF was very generous and very helpful in helping us push the type 1 diabetes aspect of it. So though we started later with it, they literally moved us forward.<\/p>\n

 <\/p>\n

So when you think about a time frame, is it years? Is it decades?<\/strong><\/em><\/p>\n

No, no. Our goal is to be ready to start testing in humans within two years.<\/p>\n

 <\/p>\n

So start clinical trials in two years? <\/strong><\/em><\/p>\n

Yes, but obviously there are lots of ifs in between.<\/p>\n

 <\/p>\n

What are the next steps for you, in terms of bringing the nanoparticles from the lab to the clinic?<\/strong><\/em><\/p>\n

To optimize the nanoparticles, and there are two aspects to that. One is to finalize whether we need to incorporate additional antigens or additional proteins into the nanoparticles, as a way of identifying as many insulin-producing cells as we can. The second is to establish our ability to produce the nanoparticles in large quantities under quality-controlled conditions that allow us to put them into people. Because obviously the requirements are different when you do the experiments in mice than in people, where you have to have very well-characterized quality-control parameters. That\u2019s why we have to form a company, because that\u2019s not something you would usually get funding for in the research sphere.<\/p>\n

 <\/p>\n

Are there other challenges that you see?<\/strong><\/em><\/p>\n

Actually, just the production of them and the standardization. That\u2019s not trivial. I think that\u2019s a challenge for everyone working in the nanoparticle space. But this type of challenge has always been present in the history of new drugs.<\/p>\n

 <\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

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