NMO | For his role in developing an antibody-fighting antibody, University of Colorado School of Medicine neurologist Jeffrey Bennett, MD, PhD, last month earned “Inventor of the Year” honors from the CU Technology Transfer Office (TTO).

Bennett, working with researcher Alan S. Verkman, MD, PhD, of the University of California, San Francisco (UCSF) and CU neurology colleage Gregory Owens, PhD, created a treatment for neuromyelitis optica (NMO), a rare autoimmune disease that predominantly attacks the optic nerves and spinal cord. It causes significant vision loss and paralysis in the majority of the patients who have it, Bennett said. People of Asian and African descent are most frequently affected.

With the help of the TTO, which provides commercial and patent support for CU researchers, Bennett and his collaborators have cofounded a venture-backed start-up company to perfect and market the technology they developed.

Because it is a demyelinating (nerve sheath-attacking) disease, NMO was for many years thought to be a far less common variant of multiple sclerosis (MS), which launches a much broader attack on the brain and spinal cord, Bennett said. In fact, long before he focused on NMO, Bennett had worked with Owens to unlock the cause of MS.

“Demyelinating disease is a significant problem in the neurology community,” Bennett said. As with any autoimmune disease, an important goal was to identify the target of the immune system, he said, and then figure out how to stop or disrupt the attack.

In 2004, researchers at the Mayo Clinic published a study showing that in patients with NMO, a particular antibody targets a protein called aquaporin-4 that is responsible for conducting water through cell membrane in the brain and spinal cord. The antibody binds to this water channel and signals the immune system to attack. Damage to the nerve sheath occurs during the fray.

“We had a demyelinating disease with a proven target,” Bennett said.

The question was how to disrupt the process. Simply put, Bennett, Owens and Verkman isolated NMO-causing antibodies, reverse-engineered them to understand how they worked, then developed benign antibodies to block the ones triggering the disease. “It’s a competitive blocker of the pathologic antibody circulating in the patient,” Bennett said. “Our antibody is specific to the target of the disease.”

Bennett called the treatment “like a laser” compared to the “sledgehammer” of the current standard of care for NMO: immunosuppressant drugs that leave the patient at great risk of infection.

Bennett estimated that developing a final compound to be used in clinical trials will take about one or two years. He envisions the treatment as an intravenous infusion, administered on an as-needed basis or regularly. Unlike MS, Bennett explained, which develops progressively, NMO strikes with sudden attacks. That means a treatment would provide immediate help.

“Everything with NMO is attack related, so if you stop the attack, you stop the disease,” he said. “We could give it during an attack or regularly to help limit the damage.”

NMO is an “orphan disease” – one that affects fewer than 200,000 people – which explains why there has been, at least until recently, minimal pharmaceutical industry interest in developing a therapy. But Bennett sees strong clinical and financial opportunities in the new technology.

“It could be attractive two ways. As an infusion therapy, it offers constant protection, but it can also be used in single dosages to stop on-going attacks,” he said. “We could also use it as an add-on to other treatments because it doesn’t suppress the immune system.”

He readily acknowledges he was a novice – at best – when the time came to switch his attention from science to business and think about how the lab breakthroughs he and his colleagues made could benefit the wider world.

“I’ve never gone through the inventing process,” Bennett said. He entered into discussions with the TTO, first to see if the invention was worthy of broader distribution. With that settled, the TTO guided him through the patenting process, which was complicated by the fact that two institutions – CU and UCSF – were involved and would share rights.

Negotiations with pharmaceutical companies and prospective venture capital partners followed, with an eleventh-hour decision made to go the do-it-yourself route and start up a new company.“I learned a lot about selling an idea,” Bennett said.

He’s optimistic about the future. “There is greater interest in orphan diseases, and there are multiple trials being developed for NMO,” he said. “But they are all based on immunosuppression. That’s our advantage. This is a ripe field for new scientific inquiry into diseases of the central nervous system.”