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University of California, Los Angeles researchers said that during Alzheimer’s earliest stages, levels of specific proteins in the blood and spinal fluid begin to drop as the disease progresses, making them potentially useful as biomarkers to identify and track progression long before symptoms appear. Identifying patients at the clinically “silent” stage is a prerequisite for advancing the strategies needed to prevent the symptoms from appearing, said the researchers in the current issue of the journal Neurology. The two basic types of the disease are sporadic Alzheimer’s and Familial Alzheimer’s, which is inherited so that all offspring in the same generation have a 50-50 chance of developing Familial Alzheimer’s if one of their parents had it. Knowing that the extracellular plaques characteristic of Alzheimer’s that form in the brain consist largely of a fibrous beta-amyloid protein called AB42, the researchers looked at that protein and found that it was elevated in the plasma of Familial Alzheimer’s mutation carriers, appearing long before the development of obvious dementia. The level then appears to drop as the disease progresses, researchers said. In addition, the researchers showed that the ratio of AB42 to another protein, AB40, was reduced in the cerebrospinal fluid of Familial Alzheimer’s mutation carriers and, further, that the levels of two other proteins, called t-tau and p-tau181, were elevated prior to overt symptoms.

 

PHARMING: PLANTS COULD MAKE VACCINES FOR TREATING TYPE OF CANCER
Plants could act as safe, speedy factories for growing antibodies for personalized treatments against a common form of cancer, according to researchers at Stanford University School of Medicine. The findings came in the first human tests of an injectable vaccine grown in genetically engineered plants. The findings, published in the advance online issue of the Proceedings of the National Academy of Sciences, said the treatments, which would vaccinate cancer patients against their malignant cells, could lead to earlier personalized therapy to tackle follicular B-cell lymphoma, an immune-system malignancy diagnosed in about 16,000 people each year. Doctors regard follicular B-cell lymphoma as a chronic, incurable disease. The standard treatment, chemotherapy, has such severe side effects that patients often opt for watchful waiting in the early stages of illness. However, plant-grown vaccines, which lack side effects, could allow earlier, more aggressive management of the cancer. Because each person’s cancer antibody is unique, every patient needs a personalized vaccine. Growing personalized vaccines in animal cells takes months, costs thousands of dollars per patient and comes with the theoretical risk that a patient might inadvertently be infected with an animal virus that contaminated the cells used to grow the vaccine. Personalized vaccines could also be produced with genetically engineered bacteria, but bacteria-grown vaccines aren't ideal, either.

 

Concord, California-based Cerus said that it has entered exclusive agreements with key distributors to supply its INTERCEPT Blood System for platelet and plasma in Chile, Indonesia, and Poland. These new distributor relationships broaden the company’s access to markets for the INTERCEPT Blood System, which is already marketed in over 30 countries in Europe, Asia and the Middle East. The INTERCEPT Blood System is used to inactivate harmful pathogens that may be present in donated blood.

 

HIV: GILEAD INITIATES LATE-STAGE CLINCIAL TRIAL OF INVESTIGATIONAL INTEGRASE INHIBITOR
Foster City-based Gilead Sciences said that it has begun enrolling patients in a late-stage clinical trial of its investigational antiretroviral agent elvitegravir (GS 9137), a novel oral integrase inhibitor that is being evaluated for the treatment of HIV-1 infection. Unlike other classes of antiretroviral agents, integrase inhibitors interfere with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells. The study is designed to assess the non-inferiority of ritonavir-boosted elvitegravir, dosed once daily, compared to raltegravir, another integrase inhibitor that is dosed twice daily. The study will enroll 700 HIV-infected, treatment-experienced patients at approximately 125 sites in the United States and Puerto Rico. A second Phase III study with a similar design involving 700 HIV-infected, treatment-experienced patients will be initiated later this year in Europe, Canada and Australia.

 

PARKINSON’S: MICHAEL J. FOX FOUNDATIONS AWARDS GRANT TO DEPOMED
Menlo Park, California-based Depomed said that it has been awarded a preclinical grant by The Michael J. Fox Foundation under the foundation’s Therapeutics Development Initiative 2008 Program. The grant, described as “modest,” supports Depomed in the development of novel gastric retentive controlled-release dosage forms of Levodopa/Carbidopa under the hypothesis that Levodopa/Carbidopa’s window of absorption in the upper gastrointestinal tract can be optimized using Depomed’s AcuForm technology. Conceptually, gastric retentive controlled-release could smooth out blood level fluctuations of Levodopa/Carbidopa and lead to more consistent efficacy. One of the major unmet needs in the treatment of Parkinson’s Disease is inconsistent efficacy and 4-6 times daily dosing of Levodopa/Carbidopa.

 

EBOLA: SCRIPPS SCIENTISTS FIND STRUCTURE OF CRITICAL VIRUS PROTEIN
Researchers at the La Jolla, California-based Scripps Research Institute have uncovered the structure of a critical protein from the Ebola Virus that allows viral entry in human cells. The structure reveals how this critical piece of the virus is assembled and helps explain how the pathogen evades and exploits the human immune system, the researchers said. There is currently no cure for Ebola hemorrhagic fever. The virus is spread when people come into contact with the bodily fluids of someone who is already infected. Most ultimately die from a combination of dehydration, massive bleeding, and shock. The findings, reported in the journal Nature, reveals the shape of the Ebola virus “spike” protein, which is necessary for viral entry into human cells. The Scripps discovery of this structure provides a major step forward in understanding how the deadly virus works, and may be useful in the development of potential Ebola virus vaccines, or treatments for those infected.

 

LIVER DISEASE: JENNEREX REPORTS EARLY-STAGE CLINICAL RESULTS FOR FIRST-IN-CLASS TREATMENT
San Francisco-based Jennerex and its South Korean partner Green Cross reported that an early-stage clinical trial of its first-in-class lead product JX-594, a cancer biotherapeutic from a proprietary class of targeted and armed oncolytic poxviruses, demonstrated the product was well-tolerated and resulted in clear anti-cancer efficacy in patients with liver cancer. Three patients with advanced treatment-refractory hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) were treated with JX-594. Objective radiographic responses were demonstrated. Serum tumor markers, which correlate with tumor burden over time in patients, decreased by up to 95 percent after treatment. JX-594 replication, its release into the circulation and distant tumor targeting and infection were demonstrated. JX-594 administration resulted in tumor vascular shutdown. Oncolytic virotherapy was also shown, for the first time, to suppress underlying HBV replication in HCC patients by over 50 percent in all three patients. A Phase II clinical trial is now underway for JX-594 in liver cancer. The data were published in the journal Molecular Therapy.

 

SLEEP DISORDERS: SRI IDENTIFIES RARE SLEEP-ACTIVATED NEURONES IN CEREBRAL CORTEX
Menlo Park, California-based SRI International said a research team has identified the first example of neurons that are activated in the cerebral cortex during slow wave sleep. The research, published in the Proceedings of the National Academy of Sciences, show that a group of rare neurons are active during slow wave sleep. For years, researchers have hypothesized that slow-wave activity is correlated with the recuperative properties of sleep and the brain’s ability to learn, in part, because brain cells are relatively quiet during this time. While populations of neurons activated during sleep have been identified in the forebrain and the hypothalamus, up until this point, neurons in the cortex have been seen as dormant. These new results show that a group of rare neurons are active, rather than at rest, during slow wave sleep. The researchers said these neurons will be important to study in sleep disorders such as insomnia. Activation of these cells during sleep may have important implications for aspects of our behavior and cognitive activities that depend heavily on sleep, such as our daytime performance, memory and mood.

 

Scientists at the Salk Institute for Biological Studies in La Jolla, California said that the cells that comprise a specialized niche in the testis of fruit flies actually emerge from adult stem cells, a finding they say has implications for regenerative medicine, aging research, and cancer therapeutics. Previously, researchers thought that a fruit fly’s allotment of testis niche cells was handed out at birth and meant to last a lifetime, said the report in the July 20 advance online edition of the journal Nature. Researchers said the findings demonstrate that once a fly becomes an adult, some stem cells that function in spermatogenesis start making the very cells that support them. Once a fly develops into an adult, some of these niche cells can be replaced, the researchers said. The researchers used microscopy and fluorescent markers enabling them to image specific cell types over time, allowing them to spot a testis stem cell population in the process of turning into their own niche, known in the fly testis as the hub. Fruit flies aren’t humans and researchers said the issues raised by this study will have to be addressed in humans before good stem cells are exploited or bad ones are eradicated.

 

The iTunes digital music software made by Cupertino, California based-Apple has the ability to manage and organize PDF files just as easily as music files, allowing radiologists to better organize their personal files of articles and images, according researchers at Renji Hospital and Shanghai Jiaotong University School of Medicine in Shanghai, China. Most published medical papers are now available on the Internet in a PDF format, providing richer information including cases and valuable images than conventional textbooks. But researchers in the July issue of the American Journal of Roentgenology said managing PDF files can be troublesome, and it is difficult to find software designed for organizing them. The researchers said iTunes can address the problem of filing multi-subject articles due to its powerful search and sort functions, its ability to remember a user’s favorite articles and its capability to support customized shortcuts for different topics and/or categories. Researchers said doctors can search, describe, and rate PDFs just like they do the music files and that they no longer need to keep PDF files in redundant folders.

THYROID CANCER: EXELIXIS STARTS LATE-STAGE TRIAL OF ANTICANCER COMPOUND

South San Francisco, California based Exelixis said it has started its phase 3 registration trial of it small molecule anticancer compound XL184 as a potential treatment for medullary thyroid cancer. XL184 is a small molecule anticancer compound targeting the MET, RET, and VEGFR2 receptor tyrosine kinases, the company said. Recently, Exelixis and the U.S. Food and Drug Administration reached agreement on the phase 3 registration trial via the Special Protocol Assessment process. Exelixis has also discussed the trial design with European regulatory agencies. The trial is a randomized, placebo-controlled, double-blinded study of XL184 as single-agent therapy in 315 patients with unresectable, locally advanced, or metastatic medullary thyroid cancer. The primary endpoint will be duration of progression-free survival, the company said. The initiation of the trial is based on encouraging data that were presented at the 2008 annual meeting of the American Society of Clinical Oncology (ASCO), the company said. Safety and clinical activity data were presented from an ongoing phase 1 trial of XL184 in 69 patients with various solid tumors, including 17 MTC patients evaluable for response. These data showed a disease control rate (percentage of patients with partial responses or prolonged stable disease greater than 3 months) of 100 percent in the evaluable patients, with 53 percent of those patients (9 of 17) experiencing partial responses, the company said. Most of the patients in the trial had previously failed other treatments, the company said.