Under the Microscope with Camillo Ricordi, M.D.

If you traveled to Spain or Japan, Italy or Argentina, Israel or China — or many other countries in between — you could find top diabetes researchers working on parts of the DRI BioHub. This multinational effort is part of the DRI’s strategy to accelerate research and overcome barriers to making progress toward a cure, be they economic, regulatory, political or otherwise.

While the DRI is based in Miami, FL, it is the hub of the DRI Federation, a worldwide network of 35 research centers.

“We have become a global enterprise that is unprecedented in academic medicine,” said DRI’s Scientific Director Camillo Ricordi, M.D.

In addition to the Federation, the DRI is part of The Cure Alliance, a group of scientists working to cure different diseases.  They share strategies and results, believing that what they learn about one disease could help cure another.

Such collaboration is a core value of the DRI. It’s never been more important than now – as we push to accelerate the development of the DRI BioHub.  

Since the BioHub was announced in March, it has received a tremendous amount of attention.
People with diabetes and their families are excited about the potential, and have been asking many important questions.

To get answers, we went “Under the Microscope” with DRI Director Camillo Ricordi, M.D.

When will the BioHub be available to patients?

We are aggressively moving the BioHub toward clinical trials. We anticipate that the first clinical trials to test components of the BioHub will take place in 2014, and we’ve already started down the regulatory path with the FDA. We will test transplanting islets alone within scaffolds made of clinical grade silicone. This material has been used clinically in many applications and therefore should more easily receive FDA approval. The study will also evaluate the placement of this BioHub platform within the omentum (abdominal lining) and its ability to regulate blood sugar levels.

We also are submitting protocols to the FDA in collaboration with Dr. Suzanne Ildstad at the University of Louisville, and with Northwestern University, to perform the first trials that will specifically target islet transplantation that completely remove anti-rejection drugs.

So it’s very exciting.

How can people enroll in the clinical trials?

The best way to remain informed as to when clinical trials will begin is by becoming a DRInsider. For sure, we will announce it and it will be known when enrollment will begin. We expect to be enrolling patients possibly before the end of this year and for sure next year.

What progress have we seen leading up to these clinical trials?

We have tested several components of the BioHub in sub-human primates, including co-transplanting islets with “helper” cells (mesenchymal stem cells) within the scaffold platform, and testing this within an omental pouch (an abdominal lining).

We have also tested our conformal coating cell encapsulation strategy in which we “shrink wrap” the islet cells with a protective barrier. After several modifications, the coatings were able to protect transplanted islets from rejection while maintaining normal blood sugar levels in the experimental models. In these studies, diabetes was reversed in less than one week and the islets continued to function long term without the use of any anti-rejection drugs.

We also are conducting clinical trials at collaborating DRI Federation centers, showing that it is possible to substantially decrease immunosuppression after infusion of mesenchymal stem cells.

Clinical trials at collaborating Cure Alliance centers are indicating that it is possible to discontinue anti-rejection drugs after tolerance-inducing protocols.

We now have new immunomodulatory molecules that were not available a few years ago.  These already have been shown to be effective in reversing type 1 diabetes in experimental model systems.

We now have oxygen-generating technology and drug delivery systems to optimize the local micro-environment of the BioHub, which were not available a few years ago.

All of these advances make us increasingly optimistic about our ability to successfully transfer these components to the BioHub platform — and that biologic replacement of insulin producing cells without systemic immunosuppression is within our reach.

The BioHub is a combination of several interrelated strategies. How do you envision these emerging?

I see us restoring self-tolerance and eliminating autoimmunity by inducing chimerism (ongoing collaboration with Cure Alliance’s Dr. Suzanne Ildstad from University of Louisville and collaborators).

The same technology already has been successful in eliminating immunosuppression — anti-rejection drugs — in organ transplantation. That’s been working for more than three years and counting.  We believe we can use this when transplanting insulin-producing cells within the BioHub

The additional technologies incorporated in the BioHub could represent alternative or complementary ways to avoid treating the recipients with anti-rejection drugs. That remains the central objective of the entire project.

The BioHub will eventually be applicable to any source of insulin-producing cells. Using islets is just the first, not the final, step.

What source of islets do you believe holds the most promise for widespread use?

The DRI is pursuing a number of cell sources. These include porcine (pig) islets since pig insulin is almost identical to human insulin with the exception of one amino acid; regenerating islet cells from a patient’s precursor cells; reprogramming (transdifferentiating) other cell types in the body to become insulin-producing cells; and different sources of stem cells.

Who will be eligible to receive a BioHub? People of all ages who have type 1 diabetes? What about those with type 2?

For now, the BioHub is focused on type 1 diabetes. However, it could benefit many people with type 2 by providing healthy insulin-producing cells to override or replace their lost and/or defective cells.

Participants for initial trials will probably be required to meet the same criteria as those eligible for current Clinical Islet Transplantation (CIT) trials.

Some of the criteria include: ages 18-65, more than five years with diabetes and the inability to sense low blood sugar (hypoglycemic unawareness).

Our ultimate goal is to avoid the need for any immunosuppressive drugs, which will open the door to treat children and adults alike.

What do you see as the main challenge in getting the BioHub through clinical trials?

The main challenge is the relative complexity of the platform technology – the fact that there are several parts to the BioHub. Regulatory agencies are used to evaluating the testing of one variable at a time, so this could introduce delays. 

That’s why we choose to move in parallel. So, while we are testing the scaffold in a pilot trial here, we may be testing a new immunomodulatory strategy with centers in Europe. In Canada, we may test another approach for an alternative site of implantation, and so on.

All of these components working in parallel will allow us to move the project forward as fast and efficiently as possible. Still, I believe the barriers are not just scientific but also possibly regulatory.

When an announcement like the BioHub is made, there is concern about “hype,” or raising false hopes. How sensitive are you to this?

We are always cautious not to raise false hopes about potential cures. But we continue to work with the intensity, the concentration and the relentless effort as if the next trial could be the last one. Progress and momentum have never been so promising. Yes, I have been optimistic before, but I will continue to move with the same degree of enthusiasm as I had five or 10 years ago. To me, someone who thinks that a cure could be farther than 5-7 years from now should work on something else — maybe a mouse model where there is plenty of funding available, and where no one will ask or verify whether something is clinically relevant and/or to make a concrete effort toward timely translation to the clinical setting. 

I maintain my optimism and determination not to stop and to keep the focus on the cure.

(DRIFocus Fall 2013)

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