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Archive - Mar 25, 2015

Custom-Designed Nanocarrier Permits Synchronous Drug Combination Delivery Addressing Some Problems of Chemotherapy for Pancreatic Cancer; New Approach Could Also Reduce Treatment Cost and Side-Effects

Scientists at UCLA’s California NanoSystems Institute and Jonsson Comprehensive Cancer Center (photo) have combined their nanotechnology expertise to create a new treatment that may solve some of the problems of using chemotherapy to treat pancreatic cancer. The study, which was published online on March 16, 2015 in an open-access article in ACS Nano, describes successful experiments to combine two drugs within a specially designed mesoporous silica nanoparticle that looks like a glass bubble. The drugs work together to shrink human pancreas tumors in mice as successfully as the current standard treatment, but at one twelfth the dosage. This lower dosage could reduce both the cost of treatment and the side effects that people suffer from the current method. The study was led by Dr. Huan Meng, Assistant Adjunct Professor of Medicine, and Dr. Andre Nel, Distinguished Professor of Medicine, both at the Jonsson Cancer Center. Pancreatic cancer, a devastating disease with a five-year survival rate of just 5 percent, is difficult to detect early and symptoms do not usually appear until the disease is advanced. As a result, many people are not diagnosed until their tumors are beyond the effective limits of surgery, leaving chemotherapy as the only viable treatment option. The chemotherapy drug most often used for pancreas cancer is gemcitabine, but its impact is often limited. Recent research has found that combining gemcitabine with another drug called paclitaxel can improve the overall treatment effect. In the current method, Abraxane — a nano complex containing paclitaxel — and gemcitabine are given separately, which works to a degree, but because the drugs may stay in the body for different lengths of time, the combined beneficial effect is not fully synchronized.

Former ASHG President Aravinda Chakravarti Leads Novel Effort That Identifies New Gene for Autism--"Treasure Your Exceptions"

Using a novel approach that homes in on rare families severely affected by autism, a Johns Hopkins-led team of researchers has identified a new genetic cause of the disease. The rare genetic variant offers important insights into the root causes of autism, the researchers say. And, they suggest, their unconventional method can be used to identify other genetic causes of autism and other complex genetic conditions. A report on the study was published online on March 25, 2015 in Nature and is scheduled for print publication in the April 2, 2015 issue of the same prestigious journal. The title of the Nature article is "Loss of δ-Catenin Function in Severe Autism." In recent years, falling costs for genetic testing, together with powerful new means of storing and analyzing massive amounts of data, have ushered in the era of genome-wide association and sequencing studies. These studies typically compare genetic sequencing data from thousands of people with and without a given disease to map the locations of genetic variants that contribute to the disease. While genome-wide association studies have linked many genes to particular diseases, their results have so far failed to lead to predictive genetic tests for common conditions, such as Alzheimer's, autism, or schizophrenia. "In genetics, we all believe that you have to sequence endlessly before you can find anything," says Aravinda Chakravarti (photo), Ph.D., a Professor in the Johns Hopkins University School of Medicine's McKusick-Nathans Institute of Genetic Medicine, Director of the Center for Complex Genomics, and a past President of the American Society of Human Genetics (ASHG). "I think whom you sequence is as important, if not more so, than how many people are sequenced."

TheraMAB Resurrects Novel Regulatory T-Cell Activator Drug (TAB08) That Once Had Disastrous Clinical Results, But May Be Effective and Safe at Much Lower Doses

TheraMAB, a small German-Russian biotech firm presented new data on its drug theralizumab (TAB08) in Nature Biotechnology’s December 2014 special issue on Biopharma Dealmakers. The link to this open-access article is provided at the end of this story. According to the article, TheraMAB is progressing in the clinical development of this novel regulatory T-cell activator for use in rheumatoid arthritis and other autoimmune diseases based on encouraging interimresults of its continuing phase 1b clinical trial. The mechanism of action and good preclinical data suggest that TAB08 may also be effective for treating autoimmune diseases such as systemic lupus erythematosus (SLE) and psoriasis. Following the company’s presentation of data at the Bio 2014 conference in June 2014, TheraMAB CEO Dr. Dimitry Tyrsin was encouraged to publish the company’s interesting data on this drug in Nature Biotechnology. In this Nature Biotechnology article, TheraMAB overviews the history of the drug molecule, and reviews the novel methods used to further characterize mechanism of action of TAB08 in preclinical models. Special attention is brought to recent clinical data in healthy volunteers and patients with rheumatoid arthritis. It has been demonstrated that theralizumab (TAB08) can be administered safely to healthy volunteers and rheumatoid arthritis patients, and preliminary phase 1b findings show promising clinical effect data. “The presentation of our phase 1a/b results at recent meetings has drawn significant interest from both scientists and clinicians,” said Dr. Tyrsin. “The results obtained are very encouraging. TAB08 has the potential to meet the substantial medical need of patients suffering from rheumatoid arthritis and other autoimmune diseases.

Dysfunctional Tau Protein, Not Amyloid, Drives Cognitive Decline & Memory Loss in Alzheimer’s; Therapeutics Should Target Tau, Mayo Clinic Study Claims

By examining more than 3,600 postmortem brains, researchers at Mayo Clinic's campuses in Jacksonville, Florida, and Rochester, Minnesota, have found that the progression of dysfunctional tau protein drives the cognitive decline and memory loss seen in Alzheimer's disease. Amyloid, the other toxic protein that characterizes Alzheimer's, builds up as dementia progresses, but is not the primary culprit, they say. The findings, published online on March 24, 2015 in an open-access aarticle in Brain, offer new and valuable information in the long and ongoing debate about the relative contribution of amyloid and tau to the development and progression of cognitive dysfunction in Alzheimer's, says the study's lead author, Melissa Murray, Ph.D., a neuroscientist at Mayo Clinic in Jacksonville. The findings also suggest that halting toxic tau should be a new focus for Alzheimer's treatment, the researchers say. "The majority of the Alzheimer's research field has really focused on amyloid over the last 25 years," Dr. Murray says. "Initially, patients who were discovered to have mutations or changes in the amyloid gene were found to have severe Alzheimer's pathology -- particularly in increased levels of amyloid. Brain scans performed over the last decade revealed that amyloid accumulated as people progressed, so most Alzheimer's models were based on amyloid toxicity. In this way, the Alzheimer's field became myopic." But researchers at the Mayo Clinic were able to simultaneously look at the evolution of amyloid and tau using neuropathologic measures. "Imagine looking at the rings of a tree -- you can identify patterns, like the changing seasons and the aging of the tree, when viewing the tree's cross-section," Dr. Murray says.

Merck Phase III Trial of Anti-PD-1 Drug (Keytruda) Meets Co-Primary Endpoints As First-Line Treatment for Advanced Melanoma and Trial Will Be Stopped Early; Keytruda Found Superior to Ipilimumab

Merck (NYSE:MRK), known as MSD outside the United States and Canada, announced on March 24, 2015 that the randomized, pivotal Phase 3 study (KEYNOTE-006) investigating KEYTRUDA® (pembrolizumab) compared to ipilimumab in the first-line treatment of patients with advanced melanoma has met its two primary endpoints of progression-free survival and overall survival. The trial will be stopped early based on the recommendation of the study’s independent Data Monitoring Committee. In the KEYNOTE-006 trial, KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in overall survival and progression-free survival compared to ipilimumab. The safety profile of KEYTRUDA in this trial was similar to the safety profile previously reported in advanced melanoma. KEYTRUDA is the first anti-PD-1 therapy to demonstrate a survival advantage compared to the standard of care for the first-line treatment of advanced melanoma. These data will be presented in the opening plenary session at the American Association of Cancer Research (AACR) Annual Meeting in Philadelphia, Pennsylvania, April 18-22, 2015. "Evidence from our clinical program for KEYTRUDA will help to define the appropriate treatment of advanced melanoma," said Dr. Roger Perlmutter, President, Merck Research Laboratories. "We greatly appreciate the efforts of our investigators and their patients in this important study, and we look forward to the presentation of overall survival data from KEYNOTE-006 at the AACR annual meeting." KEYNOTE-006 was a global, open-label, randomized, pivotal, Phase 3 study (, NCT01866319) evaluating KEYTRUDA compared to ipilimumab in patients with unresectable stage III or IV advanced melanoma with no more than one prior systemic therapy.