Thymosin Beta 4 Protein Potential For Neuropathy

Today's post from pcgadvisory.com (see link below) is actually a press release from the manufacturers of Thymosin B4. According to Wikipedia, "Thymosin beta-4 is a protein that in humans is encoded by the TMSB4X gene. The protein consists (in humans) of 43 amino acids". Thymosin Beta 4 is claimed to be able to protect nerves and reduce neuropathic damage. Big claims, which are only borne out after tests on mice but the idea of this protein being able to actually repair and regenerate damaged nerves is a very seductive one. We will have to wait some time before the testing and research processes are complete but it certainly looks promising and is yet more evidence of how drug companies are now taking neuropathy much more seriously as an expansion area.

Researchers Report that Long-Term Administration of Thymosin B4 in a Diabetic Animal Model Prevents Progression of Peripheral Neuropathy and Restores Sciatic Nerve Function 
4 days ago May 2015

RegeneRx Biopharmaceuticals, Inc. (RGRX), a clinical-stage drug development company focused on tissue protection, repair and regeneration, today announced that independent researchers have reported that diabetic mice treated long-term with Thymosin B4 (TB4) have significantly improved motor and sensory function in the sciatic nerve compared to the untreated animals and that TB4 protects the nerves and reverses neurological damage in diabetic neuropathy.

The improvement is closely associated with amelioration of sciatic nerve axonal and myelin damage and an increase of intraepidermal nerve fiber density. In vitro, TB4-treated neurons derived from the diabetic mice had more extensive neurite outgrowth compared to the untreated neurons. Furthermore, the researchers identified the protein that contributes to axonal remodeling.

“These results demonstrate the positive effects that TB4 has on a well-accepted animal model of diabetic peripheral neuropathy and again confirms the ability of TB4 to repair damage and promote tissue regeneration in vivo. The positive impact of TB4 on the tissue and nerve damage, as well as on the function of the sciatic nerve, is extremely encouraging and suggests a potential role for TB4 in the treatment of diabetic peripheral neuropathy in humans. Moreover, the demonstration that reduction of glucose was not required to see the effects of TB4 is consistent with knowledge that reducing glucose levels does not ameliorate diabetic peripheral neuropathy. In addition, these new data are consistent with prior robust findings that TB4 has potent neurovascular restorative effects for both neural injury and degeneration in the central and peripheral nervous systems,” stated Michael Chopp, Ph.D., a member of the research team, Scientific Director of the Henry Ford Neuroscience Institute, and the Zoltan J. Kovacs Chair in Neuroscience Research.

“Since progressive loss of peripheral nerve function due to decreased nerve fibers and reduction in myelin is a major cause of morbidity in diabetes and in other conditions, these findings on the protective and restorative role of TB4 offer a significant potential new therapy for these patients. This study is very significant for RegeneRx as diabetic peripheral neuropathy is one of the targets for the use of RGN-352, our injectable TB4 formulation developed for systemic administration, and supports our continued investment in this area,” stated J.J. Finkelstein, RegeneRx’s president and chief executive officer.

The research was conducted by Dr. Lei Wang and her colleagues in the Department of Neurology at Henry Ford Hospital in Detroit, Michigan and the Department of Physics at Oakland University in Rochester, Michigan under a Material Transfer Agreement between Henry Ford Hospital and RegeneRx Biopharmaceuticals, Inc. The study was published in the Journal of Diabetes Research; 2015:173656. Doi: 10.1155/2015/173656, Epub 2015 Apr 7.

About Diabetic Peripheral Neuropathy

Diabetes affects an estimated 346 million people worldwide. Peripheral neuropathy is a progressive complication of diabetes and is associated with degeneration and demyelination of peripheral nerves. There is currently no effective treatment for preventing the development or reversing the progression of diabetic neuropathy. Symptoms can range from pain and numbness in the extremities to problems with the digestive system, urinary tract, blood vessels and heart and can be painful, disabling, and even fatal.

About RegeneRx Biopharmaceuticals, Inc. (www.regenerx.com)

RegeneRx is focused on the development of a novel therapeutic peptide, Thymosin beta 4, for tissue and organ protection, repair and regeneration. RegeneRx currently has three drug candidates in clinical development for ophthalmic, cardiac and dermal indications, three active strategic licensing agreements in China, Pan Asia (Korea, Japan, and Australia, among others) and in the U.S. RGN-259, the Company’s TB4-based ophthalmic drug candidate is being developed for dry eye syndrome and for the treatment of neurotrophic keratopathy (NK), both of which are being developed in the U.S through its joint venture, ReGenTree. RGN-259 has been granted orphan status by the U.S. FDA and was recently allowed by the FDA to move into phase 3 clinical trials for the treatment of patients with NK. RGN-352, the Company’s TB4-based injectable drug candidate, is a phase 2-ready drug candidate designed to be administered systemically to prevent and restore tissue damage associated with acute events such as heart attacks, strokes, and other similar injuries. RGN-137, the Company’s TB4-based dermal gel, is in phase 2 clinical development. For additional information about RegeneRx please visit www.regenerx.com.

Forward-Looking Statements

Any statements in this press release that are not historical facts are forward-looking statements made under the provisions of the Private Securities Litigation Reform Act of 1995. Any forward-looking statements involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. There can be no assurance that any research published by the Company or any third party will be able to be replicated in human conditions, disorders or injuries, or prove to be commercially valuable. There can also be no assurance that any of the Company’s drug candidates will result in any approved products in the U.S. or any other country. Please view these and other risks described in the Company’s filings with the Securities and Exchange Commission (“SEC”), including those identified in the “Risk Factors” section of the annual report on Form 10-K for the year ended December 31, 2014, and subsequent quarterly reports filed on Form 10-Q, as well as other filings it makes with the SEC. Any forward-looking statements in this press release represent the Company’s views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. The Company specifically disclaims any obligation to update this information, as a result of future events or otherwise, except as required by applicable law

http://pcgadvisory.com/news/researchers-report-that-long-term-administration-of-thymosin-b4-in-a-diabetic-animal-model-prevents-progression-of-peripheral-neuropathy-and-restores-sciatic-nerve-function/

BIO ENGINEERED DECOY PROTEIN MAY STOP CANCER FROM SPREADING

A team of Stanford researchers has developed a protein therapy that disrupts the process that causes cancer cells to break away from original tumor sites, travel through the blood stream and start aggressive new growths elsewhere in the body.

This process, known as metastasis, can cause cancer to spread with deadly effect.

"The majority of patients who succumb to cancer fall prey to metastatic forms of the disease," said Jennifer Cochran, an associate professor of bioengineering who describes a new therapeutic approach in Nature Chemical Biology.

Today doctors try to slow or stop metastasis with chemotherapy, but these treatments are unfortunately not very effective and have severe side effects.

The Stanford team seeks to stop metastasis, without side effects, by preventing two proteins -- Axl and Gas6 -- from interacting to initiate the spread of cancer.

Axl proteins stand like bristles on the surface of cancer cells, poised to receive biochemical signals from Gas6 proteins.

When two Gas6 proteins link with two Axls, the signals that are generated enable cancer cells to leave the original tumor site, migrate to other parts of the body and form new cancer nodules.

To stop this process Cochran used protein engineering to create a harmless version of Axl that acts like a decoy. This decoy Axl latches on to Gas6 proteins in the blood stream and prevents them from linking with and activating the Axls present on cancer cells.

In collaboration with Professor Amato Giaccia, who heads the Radiation Biology Program in Stanford's Cancer Center, the researchers gave intravenous treatments of this bioengineered decoy protein to mice with aggressive breast and ovarian cancers.

Mice in the breast cancer treatment group had 78 percent fewer metastatic nodules than untreated mice. Mice with ovarian cancer had a 90 percent reduction in metastatic nodules when treated with the engineered decoy protein.

"This is a very promising therapy that appears to be effective and non-toxic in pre-clinical experiments," Giaccia said. "It could open up a new approach to cancer treatment."

Giaccia and Cochran are scientific advisors to Ruga Corp., a biotech startup in Palo Alto that has licensed this technology from Stanford. Further preclinical and animal tests must be done before determining whether this therapy is safe and effective in humans.

Greg Lemke, of the Molecular Neurobiology Laboratory at the Salk Institute, called this "a prime example of what bioengineering can do" to open up new therapeutic approaches to treat metastatic cancer.

"One of the remarkable things about this work is the binding affinity of the decoy protein," said Lemke, a noted authority on Axl and Gas6 who was not part of the Stanford experiments.

"The decoy attaches to Gas6 up to a hundredfold more effectively than the natural Axl," Lemke said. "It really sops up Gas6 and takes it out of action."

Directed Evolution

The Stanford approach is grounded on the fact that all biological processes are driven by the interaction of proteins, the molecules that fit together in lock-and-key fashion to perform all the tasks required for living things to function.

In nature proteins evolve over millions of years. But bioengineers have developed ways to accelerate the process of improving these tiny parts using technology called directed evolution. This particular application was the subject of the doctoral thesis of Mihalis Kariolis, a bioengineering graduate student in Cochran's lab.

Using genetic manipulation, the Stanford team created millions of slightly different DNA sequences. Each DNA sequence coded for a different variant of Axl.

The researchers then used high-throughput screening to evaluate over 10 million Axl variants. Their goal was to find the variant that bound most tightly to Gas6.

Kariolis made other tweaks to enable the bioengineered decoy to remain in the bloodstream longer and also to tighten its grip on Gas6, rendering the decoy interaction virtually irreversible.

Yu Rebecca Miao, a postdoctoral scholar in Giaccia's lab, designed the testing in animals and worked with Kariolis to administer the decoy Axl to the lab mice. They also did comparison tests to show that sopping up Gas6 resulted in far fewer secondary cancer nodules.

Irimpan Mathews, a protein crystallography expert at the SLAC National Accelerator Laboratory, joined the research effort to help the team better understand the binding mechanism between the Axl decoy and Gas6.

Protein crystallography captures the interaction of two proteins in a solid form, allowing researchers to take X-ray-like images of how the atoms in each protein bind together. These images showed molecular changes that allowed the bioengineered Axl decoy to bind Gas6 far more tightly than the natural Axl protein.

Next steps

Years of work lie ahead to determine whether this protein therapy can be approved to treat cancer in humans. Bioprocess engineers must first scale up production of the Axl decoy to generate pure material for clinical tests. Clinical researchers must then perform additional animal tests in order to win approval for and to conduct human trials. These are expensive and time-consuming steps.

But these early, hopeful results suggest that the Stanford approach could become a non-toxic way to fight metastatic cancer.

Glenn Dranoff, a professor of medicine at Harvard Medical School and a leading researcher at the Dana-Farber Cancer Institute, reviewed an advance copy of the Stanford paper but was otherwise unconnected with the research. "It is a beautiful piece of biochemistry and has some nuances that make it particularly exciting," Dranoff said, noting that tumors often have more than one way to ensure their survival and propagation.

Axl has two protein cousins, Mer and Tyro3, that can also promote metastasis. Mer and Tyro3 are also activated by Gas6.

"So one therapeutic decoy might potentially affect all three related proteins that are critical in cancer development and progression," Dranoff said.

Protein In Urine Pregnancy

Serum Protein Electrophoresis

Serum Protein Electrophoresis

Diabetic Nephropathy Stages

HIGH PROTEIN FOODS BOOST CARDIOVASCULAR HEALTH

Eating foods rich in amino acids could be as good for your heart as stopping smoking or getting more exercise -- according to new research from the University of East Anglia (UEA)

A new study published today reveals that people who eat high levels of certain amino acids found in meat and plant-based protein have lower blood pressure and arterial stiffness.

And the magnitude of the association is similar to those previously reported for lifestyle risk factors including salt intake, physical activity, alcohol consumption and smoking.

Researchers investigated the effect of seven amino acids on cardiovascular health among almost 2,000 women with a healthy BMI. Data came from TwinsUK -- the biggest UK adult twin registry of 12,000 twins which is used to study the genetic and environmental causes of age related disease.

They studied their diet and compared it to clinical measures of blood pressure and blood vessel thickness and stiffness.

They found strong evidence that those who consumed the highest amounts of amino acids had lower measures of blood pressure and arterial stiffness.

But they found that the food source was important -- with a higher intake of amino acids from plant-based sources associated with lower blood pressure, and a higher intake from animal sources associated with lower levels of arterial stiffness.

Lead researcher Dr Amy Jennings, from UEA's Norwich Medical School, said: "This research shows a protective effect of several amino acids on cardiovascular health.

"Increasing intake from protein-rich foods such as meat, fish, dairy produce, beans, lentils, broccoli and spinach could be an important and readily achievable way to reduce people's risk of cardiovascular disease.

"Results from previous studies have provided evidence that increased dietary protein may be associated with lower blood pressure. We wanted to know whether protein from animal sources or plant-based sources was more beneficial -- so we drilled down and looked at the different amino acids found in both meat and vegetables.

"We studied seven amino acids -- arginine, cysteine, glutamic acid, glycine, histidine, leucine, and tyrosine. Glutamic acid, leucine, and tyrosine are found in animal sources, and a higher intake was associated with lower levels of arterial stiffness.

"All seven amino acids, and particularly those from plant-based sources, were associated with lower blood pressure.

"The really surprising thing that we found is that amino acid intake has as much of an effect on blood pressure as established lifestyle risk factors such as salt intake, physical activity and alcohol consumption. For arterial stiffness, the association was similar to the magnitude of change previously associated with not smoking.

"High blood pressure is one of the most potent risk factors for developing cardiovascular disease. A reduction in blood pressure leads to a reduction in mortality caused by stroke or coronary heart disease -- so changing your diet to include more meat, fish, dairy produce and pulses could help both prevent and treat the condition.

"Beneficial daily amounts equate to a 75g portion of steak, a 100g salmon fillet or a 500ml glass of skimmed milk," she added.

Prof Tim Spector from the department of Twin Research at King's college London said: "The finding that eating certain meat and plant proteins are linked to healthier blood pressure is an exciting finding. We need to understand the mechanism to see if it is direct or via our gut microbes."