Tuesday, February 20, 2018

Clinical trials for neurological diseases are long and arduous, taking many years and a lot of money to complete, so developing medications to treat those diseases is also long and arduous, taking many years and lots of money to complete.

Sometimes it takes so much time and money that researchers and pharmaceutical companies don’t bother because the probability of bringing an effective and profitable drug to market doesn’t outweigh the risk of losing their investment.

But a national network funded by the National Institutes of Health and led by the University of Iowa is accelerating the clinical trial process for neurological diseases with the expectation of bringing drugs to market in less time, with less money and less risk.

NeuroNEXT brings together 25 academic health care research institutions to create a consortium of researchers with a national reach, making it easier and less expensive to conduct clinical trials for diseases like autism, Huntington’s disease, and multiple sclerosis. The College of Public Health’s Clinical Trials and Statistical Data Management Center (CTSDMC) is the data coordinating center for the initiative, partnering with Massachusetts General Hospital to oversee all data and statistical collection and analysis and helping researchers design their trials across the 25 academic sites.

Chris Coffey portrait
Chris Coffey

Chris Coffey, director of the CTSDMC, says NeuroNEXT “de-risks” the process of developing and testing drugs and therapies, spreading the inherent risk over a number of institutions, funding agencies, and pharmaceutical companies.

“A single institution is no longer spending the resources to conduct a clinical trial,” Coffey says. “Now, the risk is shared among many institutions across the country.”

He says recruiting patients to participate in the trials is also easier when 25 institutions are involved instead of just one or two, especially in rare diseases with few patients. The network also helps with quality control, ensuring the same standards are applied across the trials and that the data are gathered in the most efficient and cost-effective way possible.

“We act as a bridge to make sure all of the trials are conducted in the same way,” Coffey says.

Ultimately, he says, the goal is to encourage more clinical trials in neurological disorders, see those trials through to completion, and if possible, ascertain whether there is enough promise to go forward in drug development. NeuroNEXT focuses exclusively on Phase II trials, which means researchers are not looking for a definitive answer to whether the treatment is effective. That happens in Phase III and requires more patients and more money. In Phase II, researchers learn more about a potential treatment and decide whether there is enough evidence to justify the cost and complexity of a larger, more definitive trial.

“We’re moving the knowledge forward,” says Dixie Ecklund, director of operations for the CTSDMC and research administrator in the College of Public Health.  

NeuroNEXT was founded in 2011, but the results of its first trial were only published in November 2017 in Annals of Neurology, a six-year gap that demonstrates just how long it takes to study neurological disease. Led by researchers at the Ohio State University, the two-year trial observed biomarkers that indicate infantile-onset spinal muscular atrophy (SMA), a genetic disease that affects the motor nerve cells in the spinal cord so that patients over time lose the ability to walk, eat, or breathe. Infants who have the disease typically don’t live longer than a few years—Coffey says more than half of the infants who started the trial did not live through to the end. The trial involved researchers at 15 NeuroNEXT sites, and the data they collected were used to supplement the data used to gain FDA approval of the drug Spinraza as an effective therapy.

“Our study showed how SMA occurred and what the progression looks like in newborns,” Coffey says. “Now that we have properly described and know how to find those benchmarks, researchers are able to match up drugs that can effectively be used against it in this study.”

A gene therapy for SMA currently in clinical trials may soon be available too.

Eight additional NeuroNEXT trials are currently in various states of completion. Some of the trials are moving forward with the expectation of creating new drugs, such as Spinraza, says Coffey. Others are testing existing drugs used to treat other diseases to see if they can be repurposed to treat neurological diseases. One such trial is to determine whether the drug Ibudilast, which has been prescribed for years in Japan to treat asthma, can be used to treat the symptoms of multiple sclerosis as well.

Other trials are looking to find treatments for diseases like Huntington’s disease, multiple sclerosis, myasthenia gravis, fragile X syndrome, and glioblastoma multiforme, the type of brain tumor currently afflicting Senator John McCain. A trial for a drug that would minimize the effects felt by stroke patients is also underway.