Substance from pine bark is a potential source for treating melanoma

A substance that comes from pine bark is a potential source for a new treatment of melanoma, according to Penn State College of Medicine researchers.

Current melanoma drugs targeting single proteins can initially be effective, but resistance develops relatively quickly and the disease recurs. In those instances, resistance usually develops when the cancer cell's circuitry bypasses the protein that the drug acts on, or when the cell uses other pathways to avoid the point on which the drug acts.

"To a cancer cell, resistance is like a traffic problem in its circuitry," said Gavin Robertson, professor of pharmacology, pathology, dermatology, and surgery and director of the Penn State Hershey Melanoma Center. "Cancer cells see treatment with a single drug as a road closure and use a detour or other roads to bypass the closure."

Penn State researchers may have solved this problem by identifying a drug that simultaneously creates many road closures.

The researchers screened 480 natural compounds and identified leelamine, derived from the bark of pine trees, as a drug that can cause this major traffic jam in the cancer cell's circuitry.

"Natural products can be a source of effective cancer drugs, and several are being used for treating a variety of cancers," said Robertson. "Over 60 percent of anti-cancer agents are derived from plants, animals, marine sources or microorganisms. However, leelamine is unique in the way that it acts."

Leelamine could be the first of a new unique class of drugs that will simultaneously target several protein pathways. Researchers found that this drug shuts down multiple protein pathways, such as PI3K, MAPK and STAT3, at the same time in melanoma cells. Thpse pathways are involved in the development of up to 70 percent of melanomas. Protein pathways like these help cancer cells multiply and spread, so shutting them down helps kill the cells.

"The cancer cell is addicted to these pathways," Robertson said. "And when they are shut down, the bypass routes cannot be used. The result is the cancer cells die."

Substance from pine bark is a potential source for treating melanoma

New drug offers promising possibility for treating adults with periodontitis

University of Pennsylvania researchers have been searching for ways to prevent, half and reverse periodontitis. In a report published in the Journal of Immunology, they describe a promising new target: a component of the immune system called complement. Treating monkeys with a complement inhibitor successfully prevented the inflammation and bone loss that is associated with periodontitis, making this a promising drug for treating humans with the disease.

George Hajishengallis, a professor in the School of Dental Medicine's Department of Microbiology, was the senior author on the paper, collaborating with co-senior author John Lambris, the Dr. Ralph and Sallie Weaver Professor of Research Medicine in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine. Their collaborators included Tomoki Maekawa, Toshiharu Abe, Evlambia Hajishengallis and Kavita B. Hosur of Penn Dental Medicine and Robert A. DeAngelis and Daniel Ricklin of Penn Medicine.

Earlier work by the Penn team had shown that the periodontal bacterium Porphyromonas gingivalis can hamper the ability of immune cells to clear infection, allowing P. gingivalisand other bacteria to flourish and inflame the gum tissue.

"P. gingivalis has many mechanisms to escape killing by the immune system, but getting rid of inflammation altogether is not good for them because they 'feed' off of it," Hajishengallis said. "So P. gingivalis helps suppress the immune system in a way that creates a hospitable environment for the other bacteria."

The researchers wanted to find out which component of the complement system might be involved in contributing to and maintaining inflammation in the disease. Their experiments focused on the third component of complement, C3, which occupies a central position in signaling cascades that trigger inflammation and activation of the innate immune system.

New drug offers promising possibility for treating adults with periodontitis

Screen of existing drugs finds compounds active against MERS coronavirus

Clinicians treating patients suffering from Middle East respiratory syndrome (MERS) currently have no drugs specifically targeted to the MERS coronavirus (MERS-CoV), a virus first detected in humans in 2012 that has since caused 614 laboratory-confirmed infections, including 181 that were fatal, according to the World Health Organization. The case count escalated sharply in the spring of this year, and the first cases in the United States were announced in early May. To address the urgent need for therapies, researchers supported by the National Institutes of Health screened a set of 290 compounds already approved by the U.S. Food and Drug Administration or far advanced in clinical development for other indications to determine if any might also show potential for working against MERS-CoV.

Screen of existing drugs finds compounds active against MERS coronavirus  

FDA Approves Dalvance (dalbavancin) to Treat Skin Infections

The U.S. Food and Drug Administration today approved Dalvance (dalbavancin), a new antibacterial drug used to treat adults with skin infections.

Dalvance is intended to treat acute bacterial skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria like Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant strains) and Streptococcus pyogenes. The treatment is administered intravenously.

Dalvance is the first drug designated as a Qualified Infectious Disease Product (QIDP) to receive FDA approval. Under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act, Dalvance was granted QIDP designation because it is an antibacterial or antifungal human drug intended to treat serious or life-threatening infections.

“Today’s approval demonstrates the FDA’s commitment to encouraging increased development and approval of new antibacterial drugs, providing physicians and patients with important new treatment options,” said Edward Cox, M.D., M.P.H, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research.

As part of its QIDP designation, Dalvance was given priority review, which provides an expedited review of the drug’s application. Dalvance’s QIDP designation also qualifies it for an additional five years of marketing exclusivity to be added to certain exclusivity periods already provided by the Food, Drug and Cosmetic Act.

Dalvance’s safety and efficacy were evaluated in two clinical trials with a total of 1,289 adults with ABSSSI. Participants were randomly assigned to receive Dalvance or vancomycin, another antibacterial drug. Results showed Dalvance was as effective as vancomycin for the treatment of ABSSSI.

The most common side effects identified in the clinical trials were nausea, headache and diarrhea. In the trials, more participants in the Dalvance group had elevations in one of their liver enzyme tests. The Dalvance drug label provides recommendations on dosage adjustment in patients with renal impairment.

FDA Approves Dalvance (dalbavancin) to Treat Skin Infections

Combination of metformin and rapamycin shows potential in treating aging and related diseases

A proven approach to slow the aging process is dietary restriction, but new research in the Linus Pauling Institute at Oregon State University helps explain the action of a drug that appears to mimic that process - rapamycin.

Rapamycin, an antibiotic and immunosuppressant approved for use about 15 years ago, has drawn extensive interest for its apparent ability - at least in laboratory animal tests - to emulate the ability of dietary restriction in helping animals to live both longer and healthier.

However, this medication has some drawbacks, including an increase in insulin resistance that could set the stage for diabetes. The new findings, published in the Journals of Gerontology: Biological Sciences, help to explain why that happens, and what could be done to address it.

They suggest that a combination of rapamycin and another drug to offset that increase in insulin resistance might provide the benefits of this medication without the unwanted side effect.

"This could be an important advance if it helps us find a way to gain the apparent benefits of rapamycin without increasing insulin resistance," said Viviana Perez, an assistant professor in the Department of Biochemistry and Biophysics in the OSU College of Science.

"It could provide a way not only to increase lifespan but to address some age-related diseases and improve general health," Perez said. "We might find a way for people not only to live longer, but to live better and with a higher quality of life."

Age-related diseases include many of the degenerative diseases that affect billions of people around the world and are among the leading causes of death: cardiovascular disease, diabetes, Alzheimer's disease and cancer.

Combination of metformin and rapamycin shows potential in treating aging and related diseases

Study provides new insight into the prevalence of obesity

Study provides new insight into the prevalence of obesity

Isis Pharmaceuticals starts Phase 1 clinical study of ISIS-PKKRx to treat patients with HAE

Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced  that it initiated a Phase 1 clinical study of ISIS-PKKRx.  ISIS-PKKRx is an antisense drug in development to treat patients with hereditary angioedemia (HAE).  HAE is a rare genetic disease that is characterized by rapid and painful attacks of inflammation in the hands, feet, limbs, face, abdomen, larynx and trachea.  HAE affects approximately 20,000 patients in the United States and Europe and can be fatal if swelling occurs in the larynx.  ISIS-PKKRx is designed to alter the course of HAE and therefore has the potential to be best-in-class for the treatment of HAE.  

Isis Pharmaceuticals starts Phase 1 clinical study of ISIS-PKKRx to treat patients with HAE

AbbVie receives HUMIRA orphan drug designation from FDA for treatment of non-infectious uveitis

AbbVie (NYSE: ABBV) announced that the U.S. Food and Drug Administration (FDA) has granted HUMIRA® (adalimumab) orphan drug designation for the treatment of non-infectious intermediate, posterior, or pan-uveitis, or chronic non-infectious anterior uveitis, a group of rare but serious inflammatory diseases of the eye. AbbVie is investigating the efficacy and safety of HUMIRA for the treatment of non-infectious uveitis, and the clinical program is in Phase III development. HUMIRA is not currently approved to treat any form of uveitis.

Uveitis is a general term that encompasses several inflammatory eye diseases. The associated inflammation causes damage of eye tissue leading to reduced vision and/or vision loss. While the exact cause of uveitis is unknown, this condition can be caused by an infection, autoimmune disease, medication, surgery or trauma to the eye. Symptoms of uveitis may include vision loss, blurred vision, eye pain and redness, as well as sensitivity to light. It is estimated that uveitis accounts for 10 to 15 percent of all cases of total blindness in the U.S.

AbbVie receives HUMIRA orphan drug designation from FDA for treatment of non-infectious uveitis

Study: RNAi silencing strategy blocks production of mutant huntingtin protein

In continuation of my update on RNAi

A targeted gene silencing strategy blocks production of the dysfunctional huntingtin (Htt) protein, the cause of Huntington's disease, a fatal, inherited neurodegenerative disorder. The effectiveness of this RNA interference (RNAi) approach in reducing levels of mutant Htt protein and disease symptoms in a mouse model of the disease is described in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Human Gene Therapy website.

Lisa Stanek and coauthors from Genzyme (Framingham, MA) used an adeno-associated viral (AAV) vector to deliver a targeted nucleic acid sequence called a small interfering RNA (siRNA) into the cells of affected mice. The siRNA selectively binds to the mutated gene, blocking disease-causing Htt production. The authors present data demonstrating the ability to deliver the therapeutic RNAi into the cells, reduce mutant Htt levels, and impact behavioral deficits in the mice without causing any noticeable neurotoxicity, in their article "Silencing Mutant Huntingtin by Adeno-Associated Virus-Mediated RNA Interference Ameliorates Disease Manifestations in the YAC128 Mouse Model of Huntington's Disease."

"The Genzyme group uses state-of-the-art delivery technology and a gene silencing approach to generate very promising preclinical data for Huntington's disease," says James M. Wilson, MD, PhD, Editor-in-Chief of Human Gene Therapy, and Director of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.

Study: RNAi silencing strategy blocks production of mutant huntingtin protein

New anticancer compound discovered

A team of research scientists from VTT Technical Research Centre of Finland, the University of Turku and the University of Eastern Finland has discovered a previously unknown Cent-1 molecule that kills cancer cells. Their research also shows that new cancer drug candidates can be identified faster and at lower cost by using computer-assisted and cell-based screening of compounds.

Ref: http://mct.aacrjournals.org/content/13/5/1054

New anticancer compound discovered