Practical science

Realistic approach

Research info

For diabetic patients, every treatment option comes with serious drawbacks: daily injections, constant changes in dosing, continued risk of side effects, or lifelong immunosuppressant drugs that are difficult on the body.

Dr. Sollinger, Dr. Alam, and the ENDSULIN team have investigated several options to make life easier for all diabetic patients. Through 25+ years of innovative and focused research at the University of Wisconsin Hospitals and Clinics in Madison, they finally unlocked an elegant answer, using the latest biotechnology.


PATIENT-DRIVEN SCIENCE

GENE THERAPY

BECAUSE IT’S MINIMALLY INVASIVE AND DURABLE ► Gene therapy is one of the most promising emerging biotechnologies, because it can cure patients for a prolonged period of time. For instance, patients receiving gene therapy treatments for hemophilia have been cured for 10 years with one treatment.

Treatment is easier on patients, and long-lasting.

GIRE

BECAUSE IT IS PRECISE ► ENDSULIN has developed a patented DNA sequence called glucose-inducible regulatory element (GIRE). It responds to glucose concentrations in the blood, then provides regulated release of insulin to accomplish blood-glucose control.

Animal experiments have achieved this type of control for the life of the animal.

It can achieve near-perfect regulation.

AAV8

BECAUSE IT’S EFFICIENT ► GIRE is packaged inside adeno-associated virus (AAV), which is not known to cause disease, but can still transfer the gene to the liver cells. AAV8 has a long-term safety record, and the FDA has approved more than 100 AAV trials.

It only takes one treatment.

HEPATOCYTES

BECAUSE THEY CAN ALREADY REGULATE GLUCOSE ► A major advantage of hepatocytes is that they can effectively produce peptides, including insulin.

The liver already has regulatory elements that, with the addition of our unique GIRE, assist in maintaining normal glucose levels. The genetically altered hepatocytes mimic the action of a normal pancreas.

Because hepatocytes don’t carry proteins on their surface (which are the target of the autoimmune disease that causes diabetes), there is no risk the autoimmune system will destroy the genetically altered hepatocytes.

It eliminates lifelong use of immunosuppressants.

TARGETED

TO MITIGATE RISK ► The therapy exclusively targets a small portion of cells so it doesn’t interrupt the liver’s regular functioning. For the treatment to work, only one in 50 liver cells need to be transduced.

Treatment can be delivered safely.

REALISTIC APPROACH

Clear regulatory path

► The AAV vector has the best chance to pass regulatory hurdles, since the only FDA-approved gene therapies at this time are based on AAV

► The approach is very similar to the previously successful research & clinical trials in animals and patients with hemophilia. We expect it will have a similar long-term safety record.

► The vector containing the GIRE will be injected intravenously, which is a low-risk intervention

Scalability

► Process development and scale-up procedures for AAV8 are already well-established by several manufacturers

► AAV8 allows for long-term storage and easy shipping

► It is expected that patients will only need 1 intravenous infusion

RESEARCH INFO

Proof of concept

ENDSULIN has proved efficacy and durability in hundreds of rodents.

Dr. Sollinger and Dr. Alam’s research, conducted at UW-Madison, has been published in several peer-reviewed scientific research journals, including PLOS ONE in June 2013.

Read it now

  • First company to publish data demonstrating that glucose control, and insulin disappearance after glucose stimuli, follow a near-perfect physiological pattern.

  • Among one of the first labs to pursue hepatocyte-based insulin gene therapy

  • The only researchers in the world testing gene therapy in large mammals for diabetes with autoimmune disease. All experts accept that for any T1DM therapy to be meaningful, it must be evaluated in an autoimmune large-animal model.