Peering into the preclinical realm

Here’s a brief roundup of some additional news items related to preclinical research that you might find of interest.

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Melligen cells prove safe in first preclinical test
SILVER SPRING, Md.—PharmaCyte Biotech Inc., a clinical-stage biotechnology company focused on developing targeted treatments for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, announced  in May that the Institute of Virology at the University of Veterinary Medicine Vienna, one of the partners in PharmaCyte Biotech’s international Diabetes Consortium, has completed the first round of safety testing of the Melligen cells in mice.
The study reportedly showed that Melligen cells are as safe as the cells that were encapsulated with the Cell-in-a-Box technology and then used together with the cancer drug ifosfamide to treat patients with advanced pancreatic cancer in previous clinical trials. This safety study is the first study of the Melligen cells in animals conducted as part of the work of the international Diabetes Consortium. Additional safety, efficacy and dose-finding studies of the Melligen cells are planned for the near future.
“We are pleased that our first test of the Melligen cells has shown favorable results. Given these results, we are moving forward with our efforts on multiple fronts to develop a treatment for insulin-dependent diabetes using PharmaCyte Biotech’s Cell-in-a-Box technology to encapsulate Melligen cells,” said Kenneth L. Waggoner, CEO of PharmaCyte Biotech. “We believe that by implanting encapsulated Melligen cells into diabetic patients, we will be able to eliminate the need for daily injections of insulin in diabetic patients. In our opinion, this therapy is at the forefront of finding a cure for type 1 diabetes and for those patients with type 2 diabetes in need of insulin.”
Melligen cells have shown promise as a potential treatment for insulin-dependent diabetes through the genetic engineering of human, non-pancreatic beta cells that makes the Melligen cells capable of regulating blood sugar levels by producing insulin on demand. In the past, when Melligen cells were transplanted into diabetic mice, the blood glucose levels of the mice became normal.
PharmaCyte Biotech has the exclusive worldwide rights to use the Melligen cells to treat diabetes. These rights were obtained from the University of Technology Sydney (UTS), where Prof. Ann Simpson, along with her colleagues at UTS, has spent years developing this unique cell line.
Nicotinamide riboside may rescue neurons subjected to trauma and disease
IRVINE, Calif.—ChromaDex Corp., a natural products company that provides proprietary ingredients and science-based solutions to the dietary supplement, food and beverage, cosmetic and pharmaceutical industries, announced in late April the results of a preclinical study performed by researchers at Washington University Medical School that were published online in the journal Science. The report was titled “SARM1 Activation Triggers Axon Degeneration Locally via NAD+ Destruction.”
The study was led by Dr. Jeffrey Milbrandt, the James S. McDonnell Professor and head of the university’s department of genetics, in collaboration with Aaron DiAntonio, the Alan A. and Edith L. Wolff Professor of Developmental Biology at the university. Their studies have focused on axon biology and the role of nicotinamide adenine dinucleotide (NAD+), of which nicotinamide riboside (NR) is an important precursor.
The researchers have noted that axon degeneration interrupts nerve signaling and prevents communication between nerves. This degeneration is common in many neurodegenerative diseases, neurological disorders and traumatic nerve injuries. Axons, the longest cellular structures in the body, possess an intrinsic, locally mediated self-destruction program that facilitates clearance of damaged axon fragments but also promotes axon loss in the context of neurological disorders. The scientists reported that the protein SARM1, an essential regulator of axon degeneration, triggers a rapid chemical breakdown of the metabolic cofactor NAD+ and, moreover, they found that this protein, once unleashed, causes a rapid decline in the energy supply within axons. Within minutes after SARM1 is activated in neurons, a massive loss of NAD+ occurs within the axon.
Working in neurons in which SARM1 was activated, the researchers showed they could completely block axon degeneration and neuron cell death by supplementing the cells with a precursor to NAD+, specifically NR. The neurons were able to use NR to keep the axons energized and healthy.
In March 2013, ChromaDex announced it had licensed from Washington University exclusive worldwide patent rights related to NR. The patent rights cover the use of NR for the prevention or treatment of neuropathies caused by axon degeneration.
Frank Jaksch Jr., CEO and co-founder of ChromaDex, commented, “This study is yet another piece of research that indicates a depletion of the metabolic cofactor NAD+ results in axon loss during injury and disease. Importantly, the study also shows that supplementation with the cell-permeable NAD+ precursor NR can block the depletion of NAD+. These findings suggest that supplementation with NR shows promise as a potential therapy for conditions involving axonal injury including trauma to the head (concussions), as well as various neurodegenerative diseases and neurological disorders.”
AuraSense announces preclinical data related to proprietary spherical nucleic acid platform
SKOKIE, Ill.—AuraSense Therapeutics, which calls itself “a pioneer in developing spherical nucleic acid (SNA) constructs as gene regulatory and immunotherapeutic agents,” recently announced a new publication in Proceedings of the National Academy of Sciences demonstrating the immunomodulatory effects of SNA constructs in preclinical models of lymphoma and non-alcoholic steatohepatitis (NASH).
In lymphoma, SNA constructs in combination with a cancer specific marker activated the immune system to specifically target the cells that express the marker. In a separate study, also reported in the publication, SNA constructs designed to repress the immune system in mouse models of NASH were able to exhibit immunoregulation and improve NASH-related scores and liver fibrosis in diabetic mouse models. Importantly, SNA constructs were significantly more potent than their linear counterparts, underscoring the importance of spatial orientation in the use of nucleic acid therapeutics.
“This publication is a further validation of the incredible potential our SNA platform holds as immunotherapeutics in a variety of disease states," said Dr. David Giljohann, CEO of AuraSense Therapeutics. “Further, we believe this approach could provide tremendous synergy with both marketed and therapies currently in development for various cancers.”
SNAs are nanoscale, spherical arrangements of densely packed and radially oriented nucleic acids. This architecture is said to overcome one of the most difficult obstacles to nucleic acid-based therapeutics: safe and effective delivery into cells and tissues of therapeutic importance without the need for additional physical or chemical methods or components. The SNAs can be designed to be extremely potent and highly targeted gene regulation and immune-modulatory agents.

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