Peptide Activates Receptor To Reduce Neuropathic Pain

Today's post from sciencedaily.com (see link below) looks at trials of ARA 290, which is a peptide. Peptides are naturally occurring biological molecules but that won't mean much to most people either. Put very simply, when neuropathic damage occurs, the nervous system's normal repair receptors are turned off. When ARA 290 is introduced, the repair receptor is reactivated, which in turn represses inflammation and restores the body's natural ability to repair damage. I know; it's incredibly difficult for the layman to understand but if you read the article, you should get the point. Basically, molecular science is being used to find a way for pain signals to be dampened and we should see that as good news. A feature of the last couple of years, is the emergence of news in the stem-cell and molecular science areas, that shows that neuropathic pain is being taken very seriously and there are serious efforts to find ways to tackle it. We don't have to understand exactly how it works but knowing that it shows progress towards a positive result for us all, is very reassuring. All we have to do now is wait and hope that they get to practical treatments as soon as possible.

Novel agent decreases neuropathic pain in patients with type 2 diabetes  Source: North Shore-Long Island Jewish (LIJ) Health System Date: December 15, 2014

Summary:

A promising profile of disease modification and pain reduction leads to proof-of-concept trials, scientists report. "The results from this study indicate a major breakthrough in the treatment of diabetes," said one expert.

Molecular Medicine, a peer-reviewed biomedical journal published by the Feinstein Institute Press, published the results of a new study reporting clinically significant pain reduction in type 2 diabetic patients. In an exploratory study conducted by Araim Pharmaceuticals, a biotech company developing novel treatments for chronic diseases, investigators also observed improvements in metabolic control in patients administered ARA 290. ARA 290 is a peptide engineered to activate the innate repair receptor, a receptor discovered by Araim scientists, which is only expressed following tissue damage or stress.

In the initial study, patients were administered ARA 290, a novel, first-in-class drug, daily for 28 days, with the purpose of evaluating its efficacy in treating neuropathic pain, a common condition among diabetics. When ARA 290 is administered, the repair receptor is activated and subsequently turns off inflammation and turns on the body's natural repair system. The short half-life of ARA 290, coupled with the restricted expression of the innate repair receptor, functions as a dual safety system to avoid potential side effects.

"The results from this study indicate a major breakthrough in the treatment of diabetes," said Kevin J. Tracey, MD, president of the Feinstein Institute for Medical Research and Editor of Molecular Medicine. "Over the years, Molecular Medicine has prided itself on publishing groundbreaking papers with implications on the broader medical community, and we're proud to have a potential disease-modifying solution to diabetes featured in the current issue."

The clinically significant results and excellent safety profile support Araim's development strategy of two future studies in 2015. First, metabolic improvement will be studied in type 2 diabetics with moderate kidney damage. Second, neuropathic pain reduction will be assessed in a multi-center proof of concept trial in type 1 diabetics. Both phase 2 clinical trials will be conducted in the United Kingdom, and patients will be dosed daily for six months to allow time for adequate tissue repair.

"We're excited to be on the cusp of the first diabetic disease modifier that demonstrates the potential to repair the complications of diabetes systemically," said Anthony Cerami, PhD, CEO of Araim Pharmaceuticals." Dr. Cerami developed the HbA1c diagnostic test, the current gold standard for diagnosing diabetes.

Story Source:

The above story is based on materials provided by North Shore-Long Island Jewish (LIJ) Health System. Note: Materials may be edited for content and length.

http://www.sciencedaily.com/releases/2014/12/141215101647.htm

RESEARCHERS IDENTIFY PEPTIDE THAT REDUCES URGE TO EAT

Researchers have identified a peptide and hormone that when administered to a specific area of the brain may reduce the desire for food. The study, which appears in the journalNeuropsychopharmacology, may one day lead to medications that treat obesity and binge eating disorders

Obesity is a complex disorder affecting more than 78 million Americans which involves an excessive amount of body fat. It increases your risk of diseases and health problems such as heart disease, diabetes and high blood pressure. Binge-eating disorder is a prevalent illness in America characterized by periods of excessive uncontrolled consumption of food, followed by uncomfortable fullness and feelings of self-disgust.

Using an experimental model, the researchers found when administering pituitary adenylate cyclase-activating peptide (PACAP), a peptide and hormone produced by neurons, in a specific area of the brain called the "central amygdala," it reduced the intake of food and led to weight loss.

According to the researchers PACAP is known for its food intake and body weight effects in the hypothalamus (the area of the brain known for controlling appetite). However, this is the first report of PACAP effects in the amygdala, a region of the brain outside the hypothalamus, involved in fear but also in the emotional component of eating.

The researchers also discovered how PACAP decreases food intake when injected in the amygdala. In general, food intake can be decreased in two ways: eating fewer meals of normal size during the day, or smaller meals. "We found that amygdalar PACAP reduces the amount of food eaten within meals, but not how many meals are consumed. In addition, we found that PACAP reduced the rate of intake of food. This means that, following administration of PACAP, models were eating more slowly," explained Valentina Sabino, PhD, assistant professor of pharmacology and psychiatry, and co-director of the Laboratory of Addictive Disorder at Boston University School of Medicine (BUSM).

In addition, they found that PACAP effects on food intake and body weight were dependent on another brain factor: the growth-hormone called brain-derived neurotrophic factor (BDNF). "The effects of PACAP on food intake and body weight were absent when it was given together with another drug that blocks BDNF signaling, suggesting that PACAP acts through BDNF," said Sabino.

The researchers believe these findings have implications for a variety of conditions, since they found not only how much food subjects ate but also how fast they ate them. "The PACAP system may hypothetically be the target of medications to treat not only obesity but also binge-eating, a disease characterized by excessive, uncontrollable consumption of food within brief periods of time," added coauthor Pietro Cottone, PhD, associate professor of pharmacology and psychiatry and co-director of the Laboratory of Addictive Disorder at BUSM.

Also contributing to this study were BU researchers: Attilio Iemolo, PhD, and Antonio Ferragud, MS.

Funding for this study was provided by the National Institute of Health (National Institute of Mental Health and National Institute on Drug Abuse), the Peter Paul Career Development Professorship, the Peter McManus Charitable Trust, and Boston University's Undergraduate Research Opportunities Program (UROP).