In Australia, firefighters do more than put out wildfires. They also raise money to exclusively fund a clinical trial for a possible treatment of MND — or Lou Gehrig's Disease (ALS), as it's called in the U.S. The trial has been four years in evolution from concept to execution, and has been conceived, designed, implemented and executed by Macquarie University. Each year, the firefighters, or "firies" as they're called in Australia, raise money by climbing 1,504 steps to Sydney Tower Eye wearing 45 pounds of gear. The tower is 309 meters or over 1,000 feet tall.

"The fundraising effort was started by a firefighter, Matt Pridham, whose best mate, Adam Regal, developed and has since died from MND. Over the years the firies have raised more than AU$3 million for the Centre for Motor Neuron Disease Research at Macquarie University,” says Dominic Rowe, professor of neurology at Macquarie University and a principal investigator in the study of a new drug being developed to treat MND called 3K3A-APC. “There are some nice analogies to the research, since 3K3A-APC puts out inflammation, which we think is critical to ALS, and the firies' job is to put out fire.”

In November, the Centre for Motor Neuron Disease began enrolling patients for a clinical trial of an experimental drug aimed at addressing the inflammatory mechanisms in MND. The product, 3K3A-APC from ZZ Biotech, a clinical stage biopharmaceutical company, is a genetically engineered variant of human activated protein C (APC) with a unique multi-modal mechanism of action that could potentially attenuate the progression of MND.

Rowe says previous research has shown that the focal inflammation that occurs as part of MND/ALS is a very early event in the disease process. Depending on where in the pathogenic process inflammation occurs, attenuating the inflammation may be beneficial by potentially slowing the rate of progression of the disease by 50% and extending survival, as well as quality of life, from three to 10 years.

The 3K3A-APC Phase 2a study does not include a placebo arm, so every patient enrolled gets active treatment. The trial begins with a series of measurements, including an MRI scan and other scans to measure inflammation in the brain, as well as blood tests and lumbar punctures before treatment begins. Those assessments are repeated after treatment to determine whether there has been a biological effect. While principally a safety study, the measurements are key to determining whether the drug changes the biology of ALS.

“The study will only involve 16 patients and it is expected to cost AU$1 million to run, but we’re very excited to be working with ZZ Biotech on this project,” Rowe says. “I spoke to Matt on the first day we had patients in and the emotion in his voice when he understood the impact of what he'd done in honor of his mate hit home that we all need to do more to address MND.”

Challenges with ALS research

There are currently no effective treatments to halt or reverse the progression of MND/ALS, although there are two medications that can slow the disease progression: Radicava, which is an antioxidant that can slow the worsening of the disease and Rilutek, which reduces damage to the motor nerves.

Several companies are looking at novel approaches to genetic forms of MND, but much still remains unknown as to why people develop the disease, Rowe says. While some MND cases are genetic, the majority are sporadic, and, while risk factors are not clearly understood, Rowe says it is highly likely that sporadic MND has environmental triggers.

“As a cause of death in Australia, MND has increased 257% over the last 30 years, and that increase has to be environmental,” Rowe says. “If we can untangle the environmental triggers we can potentially prevent sporadic MND.”

For this reason, Macquarie University is lobbying to make MND a notifiable disease in Australia so there is a system to identify who's had MND, where they live, and how long they've lived with the disease. In the U.S., some states have a state-based notification system, but the systems are not harmonized onto a single platform, so the data remains siloed. The one country that does have a notification system is France, Rowe says.

As with most rare diseases, advancing research into MND has been held back by several factors. First, since the disease is infrequent and very few health care practitioners will ever see a patient with MND, early recognition and diagnosis is tricky. And because clinical trial inclusion/exclusion criteria are skewed toward people early on in the disease, only about 10-15% of all MND patients are eligible for access to clinical trials.

According to Rowe, another issue is a lack of the needed expertise and critical mass to conduct sophisticated clinical trials.

“There is no other place in Australia that has the kit and the staff that would enable us to execute a trial like the one we’re doing for 3K3A-APC,” Rowe says.

Where progress is being made is in building awareness and raising funds to support research into MND. In Australia, FightMND has played an important role in bringing MND to the forefront, while in the U.S. the ALS Therapy Development Institute, a nonprofit biotech company, has become the world’s foremost drug discovery lab focused exclusively on MND/ALS.

“It remains an axiom that MND is not curable; we just need to be smarter about the funding and understanding the biology of the disease, and if we understand the mechanisms that underpin it, how it progresses, and susceptibility factors, perhaps it will become preventable,” Rowe says.