A publication in the June issue of the scientific journal Diabetes showed that a 2-week therapy with the drug hOKT3gamma1(Ala-Ala) slows the progression of type 1 diabetes for at least two years after treatment.
The new publication is a follow-up to the ground-breaking publication by UCSF’s Dr. Jeffrey Bluestone and Columbia University’s Dr. Kevan Herold that appeared in the New England Journal of Medicine (NEJM) in 2002. The initial study garnered international headlines, demonstrating for the first time that an antibody therapy could essentially stop diabetes in its tracks 1 year later if used early after type 1 diabetes diagnosis.
By monitoring the same patients in the NEJM study for a subsequent year, the researchers have demonstrated that the drug continues to be effective, long after treatment was finished. Two years later, patients that received the two week hOKT3gamma1(Ala-Ala) therapy showed greater residual beta cell function compared to untreated patients, meaning the drug appears to slow the autoimmune destruction of beta cells.
Because beta cells are the body’s source of insulin, the researchers surmised that if the beta cells were actually being preserved by the treatment, they would find that treated patients required less insulin. Which is exactly what they found: at the two year point in the study, those who had received hOKT3gamma1(Ala-Ala) were using significantly lower doses of insulin compared to those who had not received the drug. In fact, while untreated patients showed an average 60-70% increase in the dose of insulin required over the two year period, there was no change in the average insulin doses required by hOKT3gamma1(Ala-Ala)-treated patients over the same period.
In a related publication, the New England Journal of Medicine recently published a study led by French and Belgian researchers describing similar results using an antibody based upon the same principles as hOKT3gamma1(Ala-Ala). The lead investigator in the French study was Lucienne Chatenoud, a long-time collaborator with the Diabetes Center’s Bluestone. A short treatment with the drug ChAglyCD3 was also found to preserve residual beta-cell function in patients with recent-onset type 1 diabetes. The study lasted 18 months, using a larger patient population, and appears to corroborate the results observed with hOKT3gamma1(Ala-Ala).
“These are both very encouraging results,” says Bluestone, Diabetes Center Director and developer of the drug. “But not ones where we can sit back and celebrate just yet – there’s still room for us to do better, I’m sure of it.”
True to his word, the Herold-Bluestone team is seeking to better their results in a new clinical trial of the drug scheduled to begin in September 2005. The “AbATE Type 1 Diabetes” study will add an additional treatment with hOKT3gamma1(Ala-Ala) one year after the first, in an attempt to enhance and prolong its autoimmunity-blocking effects. The researchers believe that the second treatment will act as a sort of “booster” shot that will potentiate the drugs effects.
The AbATE Study (an acronym for “Autoimmunity-blocking antibody for tolerance in type 1 diabetes”) will be open to those 8-30 years of age who have been diagnosed with type 1 diabetes within six weeks prior to beginning therapy. The trial is sponsored by the UCSF-based Immune Tolerance Network (www.immunetolerance.org) and has clinical sites here at UCSF and in New York City, Denver, Seattle and Augusta.
More information on the study will be available on the Diabetes Center website in the coming weeks.