BioCrossroads drops dreams for hospital innovation

Sorry, IU Health.

There’s almost no chance of you becoming the next Cleveland Clinic, according to a report released last week by BioCrossroads, the Indianapolis-based life sciences business development group.
That’s because of the new demands for cost-cutting in health care, which are coming from Congress’ budget battles, the influx of baby boomers into the Medicare program and now Obamacare.
There simply isn’t the money available anymore for a hospital to replicate the 65-person staff and dedicated investment funding that Cleveland Clinic uses to turn medical innovations into high-growth companies.
This is not what IU Health or BioCrossroads wanted to hear. The leaders of both organizations had thought that IU Health individually or Indianapolis-area hospitals collectively could become engines of innovation to produce new life sciences companies.
BioCrossroads CEO David Johnson first mentioned the idea to me in early 2008, when I wrote a story about a researcher at Franciscan St. Francis Health who had stumbled on a way to diagnosis and potentially reverse autoimmune diseases.
That research did turn into a company, Redox Reactive Reagents LLC, which is trying to commercialize the technology as a diagnosis for Alzheimer’s disease. But Franciscan decided it wasn’t going to be in the startup game. It sold its stake in the company to the other owners and walked away.
About a year earlier, IU Health CEO Dan Evans had tapped his longtime friend Matt Neff to launch a venture capital arm, CHV Capital Inc., funded by some of IU Health's large endowment.
The firm has backed several Indiana life sciences companies, including Endocyte Inc., Nico Corp. and Perfinity Biosciences Inc. But it’s one attempt to commercialize research from within the IU Health system—a 2008 investment in CS-Keys Inc.—went nowhere.
The BioCrossroads report concludes that “classic innovation models such as the one resident at the Cleveland Clinic are too capital intensive to replicate.”
But BioCrossroads still sees opportunities for local hospital systems to play a major role in health care innovation, not so much by launching companies themselves, but rather by helping entrepreneurs understand the challenges that need to be fixed and then helping them test, refine and scale up their proposed solutions.
The Infuse Accelerator for digital health startups, which is being launched in Indianapolis, is trying to do exactly that. And so is the Hoosier Healthcare Innovation Challenge, an annual event where health care organizations present problems they have to IT entrepreneurs, who try to invent a solution.
A good example is Indianapolis-based Diagnotes Inc. It won the 2012 Healthcare Innovation Challenge and then worked with Community Health Network to pilot its mobile app, which allows doctors and patients to swap key medical records and images over mobile phones—yet without violating federal medical privacy laws.
Community has now signed a contract to use Diagnotes among some of its physicians.
BioCrossroads also thinks Indianapolis’ hospitals can replicate the kind of collaboration that led to the 2004 launch of the Indiana Health Information Exchange Inc., which allows hospitals to swap electronic patient records as needed from one health system to another.
Indianapolis’ hospitals could collective pitch themselves to drug and device companies to attract more of the clinical trials those companies fund, the BioCrossroads report suggested.
The hospitals could also consider forming a joint clinic that would conduct research, clinical trials and education, such as the Orthopedic Capital Clinic being launched by OrthoWorx, a BioCrossroads offshoot, in Warsaw, Ind.
None of those would have the impact of a Cleveland Clinic. But, as I’ve written elsewhere, in this age of austerity, the nature of health care innovation is going to be different than before.

View the original article here

Innovation in mouse model helps researchers distinguish disease mechanisms and biomarkers

Main Category: Urology / Nephrology
Article Date: 30 Jul 2013 - 2:00 PDT Current ratings for:
Innovation in mouse model helps researchers distinguish disease mechanisms and biomarkers

A team led by researchers at the National Institutes of Health has overcome a major biological hurdle in an effort to find improved treatments for patients with a rare disease called methylmalonic acidemia (MMA). Using genetically engineered mice created for their studies, the team identified a set of biomarkers of kidney damage - a hallmark of the disorder - and demonstrated that antioxidant therapy protected kidney function in the mice.

Researchers at the National Human Genome Research Institute (NHGRI), part of NIH, validated the same biomarkers in 46 patients with MMA seen at the NIH Clinical Center. The biomarkers offer new tools for monitoring disease progression and the effects of therapies, both of which will be valuable in the researchers' design of clinical trials for this disease.

The discovery, reported in the July 29, 2013, advance online issue of the Proceedings of the National Academy of Sciences, paves the way for use of antioxidant therapy in a clinical trial for patients with MMA. It also illustrates the mechanisms by which dysfunction of mitochondria - the power generators of the cell - affects kidney disease. Mitochondrial dysfunction is a factor not only in rare disorders, such as MMA, but also in a wide variety of common conditions, such as obesity, diabetes and cancer.

MMA affects as many as one in 67,000 children born in the United States. It can have several different causes, all involving loss of function of a metabolic pathway that moderates levels of an organic compound called methylmalonic acid. Affected children are unable to properly metabolize certain amino acids consumed in their diet, which damages a number of organs, most notably the kidneys.

"Metabolic disorders like MMA are extremely difficult to manage because they perturb the delicate balance of chemicals that our bodies need to sustain health," said Daniel Kastner, M.D., Ph.D., NHGRI scientific director. "Given that every newborn in the United States is screened for a number of inherited metabolic disorders, including MMA, there is a critical need for better understanding of the disease mechanisms and therapies to treat them."

MMA is the most common organic acid disorder and invariably impairs kidney function, which can lead to kidney failure. The most common therapy is a restrictive diet, but doctors must resort to dialysis or kidney transplantation when the disease progresses. MMA patients also suffer from severe metabolic instability, failure to thrive, intellectual and physical disabilities, pancreatitis, anemia, seizures, vision loss and strokes.

"There are no definitive treatments for the management of patients with MMA," said Charles Venditti, M.D., Ph.D., senior author and investigator in the Organic Acid Research Section of NHGRI's Genetics and Molecular Biology Branch. "This study is the culmination of collaboration with the patient community. It uses mouse modelling, coupled with innovations in genomics and biochemical analyses, to derive new insights into the causes of renal injury in MMA. Our studies have improved our understanding of the basic biology underlying MMA, created a novel animal model for testing interventions and, now, led us to the promise of a new therapy."

The researchers performed the studies using mice bred to carry gene alterations that disrupt the production of the same mitochondrial enzyme that is defective in patients with MMA. These are called transgenic mice. The enzyme, called methylmalonyl-CoA mutase (MUT), is an important component of the chemical process that metabolizes organic acids, specifically methylmalonic acid.

By measuring gene expression in the transgenic mice using DNA microarrays, researchers discovered 50 biomarkers of gene expression that each indicated declining kidney function. DNA microarrays are silicon chips with many spots to which a given molecule may bind. In this case, the DNA microarrays were used to precisely generate, with the aid of a computer program, a profile of gene expression in a kidney cell.

The researchers chose one of the biomarkers, called lipocalin-2, to test how it correlated with kidney function in 46 MMA patients. Plasma levels of this biomarker rose with kidney deterioration in patients with MMA, and may serve as a valuable indicator of MMA kidney disease progression in the clinic.

"The detection of biomarkers through microarray technology is immensely helpful in pointing to downstream pathways affected by the defective MUT activity," said Irini Manoli, M.D., Ph.D., lead author and a physician scientist and staff clinician in NHGRI's Genetics and Molecular Biology Branch. "The biomarkers provide new plasma or serum tests to follow disease progression in our patients."

Having discovered these important biomarkers of kidney function, the authors turned to kidney physiology experts on their team to explore the structural changes that occur in MMA disease. They analyzed the rate at which the kidneys filter waste from the blood. Co-author and renal physiology expert Jurgen Schnermann, M.D., and members of his laboratory at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), also part of NIH, demonstrated the early and significant decrease in this rate in MMA mice.

With further studies, the researchers identified increased production of free radicals in tissues from the mice, as well as in the MMA patients. Detection of free radicals indicates chemical instability in cells, which the researchers sought to remedy with antioxidant therapy. After treating the mice with two forms of dietary antioxidants, the researchers observed that the biomarkers of kidney damage diminished and the faltering kidney filtration rate tapered off. The findings demonstrated that readily available antioxidants can significantly affect the rate of decline of kidney function in transgenic mice, which replicate the kidney disease of MMA.

"The next step will be to translate these findings to the clinic," Dr. Venditti said. "With a progressive disorder like MMA, we are hopeful that we have achieved a laboratory success that our patients will benefit from in the near future."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our urology / nephrology section for the latest news on this subject.

Irini Manoli, Justin R. Sysol, Lingli Li, Pascal Houillier, Caterina Garone, Cindy Wang, Patricia M. Zerfas, Kristina Cusmano-Ozog, Sarah Young, Niraj S. Trivedi, Jun Cheng, Jennifer L. Sloan, Randy J. Chandler, Mones Abu-Asab, Maria Tsokos, Abdel G. Elkahloun, Seymour Rosen, Gregory M. Enns, Gerard T. Berry, Victoria Hoffmann, Salvatore DiMauro, Jurgen Schnermann, and Charles P. Venditti, "Targeting proximal tubule mitochondrial dysfunction attenuates the renal disease of methylmalonic acidemia", Published online before print July 29, 2013, doi: 10.1073/pnas.1302764110

For information about the MMA clinical trial, go to ClinicalTrials.gov and search with NCT00078078.

Learn more about the study

NIH/National Human Genome Research Institute

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

NIH/National Human Genome Research Institute. "Innovation in mouse model helps researchers distinguish disease mechanisms and biomarkers." Medical News Today. MediLexicon, Intl., 30 Jul. 2013. Web.
30 Jul. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Innovation in mouse model helps researchers distinguish disease mechanisms and biomarkers'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here