Cambria Biosciences LLC recently received grant funding from the National Institutes of Health to support its drug discovery program for neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis (ALS).
The three Phase I Small Business Innovation Research grants total more than $700,000. A grant from the National Institute of Neurological Disorders and Stroke is aimed at Parkinson's disease research. Parkinson's also is the focus of Cambria's second grant, from the National Institute of Environmental Health Sciences (NIEHS), a fact that was noteworthy to Leo Liu, president and CEO of the Woburn, Mass.-based company.
"Parkinson's is known to have significant environmental contributors, as well as genetic contributors," he said, adding that researchers began probing possible outside causes after determining the "vast majority of patients don't have it in their families."
Although genetic mutations have been discovered recently in rare familial forms of the disease, for most patients it is "an acquired dysfunction," Liu told BioWorld Today. He added that "we know to look at environmental causes because of a very striking mini-epidemic in the late 1970s in Santa Clara County [Calif.] among drug users, most of them in their late teens or early twenties."
Liu said those people began exhibiting symptoms of Parkinson's, characterized by tremors and difficulty moving and maintaining balance. Researchers eventually identified the cause as a contaminating byproduct of a synthetic opiate that went straight into the dopaminergic neurons, he said.
"It turns out there are a number of chemicals in the environment, such as pesticides, that can cause oxidative stress in cells, and that got the attention of NIEHS," Liu added.
With the grant, Cambria will be systematically looking at candidates that could cause oxidative stress, using cellular models of Parkinson's disease, which occurs when neurons die or become impaired, and they can no longer produce dopamine.
"Parkinson's disease is not that atypical from other degenerative diseases in that it has multiple causes," Liu said. "So we'll be looking at that from both an environmental and genetic perspective."
According to the National Parkinson Foundation, about 1.5 million Americans have been diagnosed with the disorder, and about 60,000 new cases are diagnosed each year. While there are treatments on the market, Liu said most seem to treat the symptoms rather than the cause. Drugs may induce the production of dopamine, but if a patient "doesn't have the neurons to make the dopamine, it's not going to make much difference."
Cambria's third grant from NIH, from the National Institute of Neurological Disorders and Stroke, is aimed at ALS, also known as Lou Gehrig's disease, which affects motor neurons and results in progressive muscle weakness that can lead to paralysis and death. Most of the treatments available are "supportive only," such as nutrition and ambulation and communication devices to help patients cope, Liu said.
Cambria plans to focus its efforts on elucidating the molecular sites of action of riluzole, the only drug approved to treat ALS, to identify a target and design more effective products or, at least, to find a target for possible compounds using cellular and animal models.
Founded in 1999, Cambria uses its high-throughput screening platform, along with genetic and physiological models, to discover new leads in the areas of neurodegenerative diseases, infectious diseases and drug rescue. The company "isn't a raw start-up, but an established revenue-generating company," Liu said, adding that most of Cambria's revenue comes from partnerships leveraging its technology platform. Cambria achieved several milestones in December from one of those partnerships, a multiyear collaboration with Dow AgroSciences LLC, of Indianapolis, to develop insecticides for crop protection and urban pests. Cambria validated target sites and functional assays for a number of lead insecticidal compounds furnished by Dow, which triggered undisclosed payments.
Research and development funding, such as the three recent NIH grants, also help fund the company's work.
Cambria had an "angel fund" round to raise money when it was founded, but Liu said the company has not conducted any other financing rounds since.
"We're probably not going to look at any major fund raising until we get products closer to the clinic," he said, estimating that to be about three years away.
Cambria has about 20 employees.