Spring 2013
Diagnostics being developed for meliodosis, muscular dystrophy

synapse: University of Nevada, Reno School of Medicine

David Aucoin at computer

AuCoin's research into causes of melioidosis will help eventually treat those in Thailand and Australia who have the disease. Photo by Theresa Danna-Douglas.

From bench to bedside: Scientific progress benefiting people

By Mike Wolterbeek and Anne McMillin, APR

Researchers at the University of Nevada School of Medicine are advancing scientific study aimed at combating human disease.

A new rapid test to diagnose melioidosis, a difficult infection to treat-and classified as a biothreat by the Centers for Disease Control and Prevention-is being optimized and tested by School of Medicine microbiologist David AuCoin.

A $600,000 National Institute of Allergy and Infectious Diseases grant through the Small Business Technology Transfer program recognizes the potential of AuCoin's work and supports making the new rapid test for point-of-care diagnosis of melioidosis available to countries where the disease is endemic.

Melioidosis, also called Whitmore's disease, is predominately an infectious disease of tropical climates, especially in Southeast Asia and northern Australia, where it is widespread.

"We have a prototype of the product in Thailand and Australia now to evaluate its effectiveness in endemic settings," AuCoin said. "There is no validated diagnostic product for melioidosis, patient samples must now be cultured, which takes three to seven days in order to diagnose the disease. Unfortunately, melioidosis can kill you well before the diagnosis is confirmed."

With the two-year grant, AuCoin's laboratory is collaborating with InBios International of Seattle on development of the Active Melioidosis Detect test. They are working closely with experts in the endemic areas who are currently evaluating the test with different sample patient types.

"Results are very encouraging," AuCoin said. "We produced a monoclonal antibody to identify the Burkholderia pseudomallei bacterium, which causes melioidosis, and then introduced it into a prototype lateral flow immunoassay diagnostic, which is a rapid dipstick test that can accept many patient sample types."

The assay is currently in the hands of researchers at the CDC for evaluation for use in laboratories across the U.S. Pre-clinical testing has begun in Thailand and Australia on archived samples collected from melioidosis patients, according to AuCoin.

The team is now working to secure STTR Phase II funding, which will provide an additional three years of product development to generate the necessary preclinical studies to submit an application to the FDA to evaluate the assay's effectiveness in comparison to other diagnostics for this disease, and then approve it for distribution via commercial means.

Over at the medical school's pharmacology department, a novel treatment in development for the most common form of muscular dystrophy is advancing towards human trials with a $308,000 boost from the Muscular Dystrophy Association.

The grant will be used to expand successful research by Associate Professor of Pharmacology Dean Burkin that has shown his laminin-111 protein therapy prevents the onset of the devastating neuromuscular disease in mouse models.

Duchenne muscular dystrophy is a lethal genetic disease that affects one in 3,500 newborn boys and is caused by mutations in the gene encoding dystrophin. At the time of diagnosis, DMD patients usually have developed significant muscle disease. The three-year grant will help determine if Burkin's therapy is effective at preventing or reversing disease progression after onset.

"We want to discover if this therapy is effective at preventing or reversing disease after it has already started," he said. "First, we will determine if laminin-111 prevents muscle damage after disease onset, preserves muscle function and improves survival of mouse models of DMD. Second, we will determine if laminin-111 prevents cardiomyopathy in mouse models of DMD.

"Finally, in collaboration with researchers at Texas A&M, we will determine if a human version of the protein prevents muscle disease in other animals afflicted with the disease. Results from these studies will pave the way towards developing human recombinant laminin-111 protein as a novel therapeutic for DMD."

Demonstrating that the human version has efficacy in animals with DMD will move this therapy closer to a FDA investigational drug application and potential human clinical trials.

"This MDA grant is a tremendous help in moving this technology forward," Burkin said. "Patients have been waiting for therapies to come about and I think we're at the cusp of major discoveries. Theoretically, laminin-111 protein therapy should be able to treat all patients with Duchenne muscular dystrophy."

Since laminin-111 is a naturally occurring protein already present in our kidneys and other tissues, Burkin said there is a better likelihood that it would not be rejected by the body.

Earlier this year, Burkin received a $100,000, two-year grant from Cure CMD to further develop his laminin-111 protein, which can replace naturally-occurring laminin and be potentially developed as a therapeutic treatment for merosin-deficient congenital muscular dystrophy type 1A (MDC1A).

"This grant will help us identify changes in gene expression as a result of this devastating and fatal childhood neuromuscular disease and examine the benefits of laminin-111 protein therapy in a mouse model of MDC1A. The grant represents the use of next generation DNA sequencing and will help us answer questions like whether or not laminin-111 stops the disease outright, or repairs muscle damage the disease has already caused," Burkin said.