A unique scientific approach to preventing, treating and, perhaps one day, curing type 1 diabetes is being coupled with JDRF’s equally innovative approach to funding such studies in a new partnership that might move the promise of a preventive therapy and improved treatment for the condition closer to reality.
“This is a very targeted therapeutic approach to addressing type 1 diabetes,” says Dr. Ted Clark, the Chief Scientific Officer for TetraGenetics, a company that has been working for the past several years on developing drugs to prevent and treat diabetes. “Our technology has the potential to effectively block the specific autoimmunity response that is responsible for causing the disease.”
JDRF believes in TetraGenetics’ innovations to the point they are putting their money and support behind the company and its approach to addressing a potential type 1 diabetes preventive therapy. It announced that one of the organization’s first investments from their new T1D Fund—a fund that specifically supports “high-impact early-stage investments to accelerate commercial development of life-changing therapies for people living with T1D”—will be made in TetraGenetics.
“We think the work they are doing could have a real impact,” says Dr. Jonathan Behr, the Managing Director of the T1D Fund. “Our belief is that this is a partnership that could show real results and change lives for the better.”
To fully understand the mechanizations of TetraGenetics’ technology and how it applies to type 1 diabetics you need to lean back to take a macro view of what causes diabetes in the first place then lean in to take a micro view of how TetraGenetics is looking at preventing and treating it.
The big picture view is that type 1 diabetes is an autoimmune disease, meaning that the body’s own immune system attacks insulin-producing beta cells in the pancreas, killing them and causing the condition.
Lean in closer and squint and you’ll discover something called “effector memory T-cells” and a component of those cells called Kv1.3 ion channel proteins. Effector memory T-cells are the specific immune cells that kill insulin-producing beta cells. “Ion channels control many functions in the body and Kv1.3 controls activation of effector memory T-cells,” Clark says.
“These effector memory T-cells are associated with the autoimmune cascade that causes type 1 diabetes and they contain high levels of the Kv1.3 ion channel proteins,” according to a news release from TetraGenetics and the JDRF.
That description belies a significant and bewitching problem with past attempts to blunt the autoimmune response that destroys beta cells. The specific cells that do the most damage are in a crowd of immuno-responsive cells. Most efforts have involved firing into the entire crowd of immuno-responsive cells in order to hit the effector memory T-cells. That, however, does serious damage to a person’s overall immune system and may even be harmful to delicate beta cells.
TetraGenetics, however, has honed in on Kv1.3 to come up with a more subtle and effective solution to the problem.
“There are functional antibodies that bind to Kv1.3 that are effective on effector memory T-cells,” says Douglas Kahn, Chairman, CEO, and President of TetraGenetics. “We want to target those cells to suppress their function or wipe them out all together.”
In other words, TetraGenetics has come up with antibodies that are specifically designed to target Kv1.3 to disrupt or kill the part of the immune system that kills beta cells.
“TetraGenetics used its proprietary technology to discover a pool of novel monoclonal antibodies that inhibit Kv1.3 activity,” according to a news release. “The monoclonal antibodies discovered by TetraGenetics can target the Kv1.3 ion channel proteins, thus having the potential to blunt the body’s attack on its own healthy beta cells. This therapy could play a role in secondary prevention and treatment of T1D, and may contribute, in combination with other therapies, to an eventual cure.”
TetraGenetics has so far developed ten such antibodies and, thanks to the investment from the T1D Fund, Kahn jokes, “we’ll spend that big pile of money on a big pile of antibodies.” He expects the company to develop a total of 25 such antibodies in the next 12 months. The next step on the path to applying these antibodies to attack the effector memory T-cells will be to “humanize” them over 18 months (meaning they will be designed to avoid attack by the body’s immune system) then analyze and test their effectiveness.
The work by TetraGenetics is not, by itself, enough to be a “cure” for diabetes, Kahn says.
“This application would be part of a combination therapy,” he says. “This approach does not replace dead beta cells, for instance.” He adds that the therapy might be most effectively applied to people shortly after they are diagnosed. Many people with type 1 diabetes have as much as 20 percent of beta cell function remaining when they are diagnosed, Kahn says.
Despite this seeming limitation, Behr, from the JDRF, is enthusiastic about the TetraGenetics’ approach.
“This is a very heterogeneous disease,” Behr says. “Some people have beta cell function at diagnosis, some do not. Some people have function years after diagnosis, others do not. We are advocating for a restaging in how we consider this disease. This might be an effective tool for people who are pre-symptomatic to help them avoid becoming diabetic.”
Bringing the technology to market is why the JDRF decided to fund TetraGenetics, but the partnership between the two groups goes beyond mere dollars and cents.
“We’ve been in dialogue with the JDRF for more than a year,” Kahn says. “That relationship is very rewarding. The value is so much more than financial. They help us connect with organizations and do better work. They are there opening the clinical door and working with us so together we can make some great things happen.”