A new ‘Smart’ nanotherapeutic technology of selectively delivering drugs to the cells of the pancreas may potentially lead to new treatments for Type I diabetes with improved efficacy and reduced side effects.

The novel technology developed by a collaboration of Harvard’s Wyss Institute and Children’s Hospital Boston focused on the injectable “smart” nanotherapeutics that can be programmed to target pancrea cells for selective drugs delivery.  Although the technology still needs significant further development before being ready for clinical use, it could potentially improve treatment for Type I diabetes.

Researchers tested the new technology using their “unique homing peptide molecule” to make nanoparticles, which in turn were programmed to deliver targeted, concentrated drugs to specific pancreas cells. It was found that the approach could increase drug efficacy by 200-fold in in vitro studies based on the ability of these nanomaterials to both protect the drug from degradation and concentrate it at key target sites, such as regions of the pancreas that contain the insulin-producing cells.  

Type 1 diabetes hits children and young adults, and is in serious need of a more targeted treatment with fewer side effects. The disease is lethal, as it involves the immune system destroying insulin-producing cells in the pancreas over time. Insulin treatments help for some, but patients over time can face kidney failure and blindness as the diabetes worsens. And not every patient benefits from treatment. As the researchers note, high-risk patients often can’t pursue existing treatments because they often need higher doses, which can lead to severe side effects and worsening health pretty rapidly.

Using nanoparticles that can be programmed to deliver drug or stem cell therapies to specific disease sites is an excellent alternative to systemic treatments because improved responses can be obtained with significantly lower therapeutic doses and hence, fewer side effects. To date, such nanotherapeutics have been developed primarily to treat cancer, since they can home in on the tumor via its leaky blood vessels. The challenge has been to develop ways to selectively deliver drugs to treat other diseases in which the tissues of interest are not as easily targeted. The research team addressed this problem by using a unique homing peptide molecule to create “smart” nanoparticles that can seek out and bind to the capillary blood vessels in the islets of the pancreas that feed the insulin-producing cells most at risk during disease onset.

The HIV prevention clinical study has been named the 2011 Breakthrough of the Year by the journal Science.

The HIV Prevention Trials Network 052 study, short named HPTN 052, was designed to access whether anti-HIV drugs could prevent sexual transmission of HIV among couples in which one partner has virus.  The trial, led by Myron S. Cohen, at the University of North Carolina at Chapel Hill, indicated that early treatment with anti viral drugs reduced HIV transmission in couples by 96 percent, according to the results published in  in the August 11 issue of New England Journal of Medicine.

In the multi-national HPTN 052 study, 1,763 heterosexual couples with one partner infected with HIV were enrolled and assigned to two study arms. In the first group, the HIV-infected partners were treated with anti-retroviral combo therapy and counseled to consistently take the medications as directed. Whereas, the HIV-infected partners in the second study group, only started to take the anti HIV drugs when their CD4+ T-cell levels dropped below 250 cells per cubic millimeter, or an AIDS-related event occurred.

The investigators observed in the first group nearly complete suppression of HIV in the blood of the study participants was achieved. An independent data and safety monitoring board found only one case HIV infection occurred among the previously uninfected partners in the early treatment group, compared with 27 cases in the second study group. The astonishing results made the committee decide in May 2011 to release of the study’s finding immediately, four years ahead of the planned completion of the trial. 

The editors at Science said in their announcement that “In combination with other promising clinical trials, the results have galvanized efforts to end the world’s AIDS epidemic in a way that would been inconceivable even a year ago”.

Dr Myron S. Cohen, leader of the study, said, “While I am obviously thrilled to have this research recognized as the Science breakthrough of the year. Witnessing the translation of this scientific discovery on a global scale truly is the best reward.”

“This research moves the field of HIV prevention science forward, leading us on a path toward curbing the HIV epidemic. It provides a new direction for HIV prevention research and is beginning to shape public health policy,” said Susan H. Eshleman, head of the Network Laboratory for the HIV Prevention Trials Network .

Several  U.S. and international organizations including the WHO and the Joint United Nations Programme on HIV/AIDS have incorporated or planned to incorporate the strategy of “HIV treatment as prevention” into their policy guidelines.

New reserch found the suppresion of a cell-surface protein N-cadherin blocks the ability of pancreatic cancer cells to migrate to other tissue and metastasize and prolongs survival by 25% in mice.

Pancreatic cancer as the fourth most common cause of cancer death in the world typically has a poor prognosis, partly because the cancer usually causes no symptoms at early stage, and not being diagnosed until it is locally advanced or metastatized to other tissues.

A new investigation, made by a team of scientists from Thomas Jefferson University Center for Translational Medicine, discovered that inhibiting a well known cell-surface protein N-cadherin on pancreatic cancer cells slows dows cancer cells’ ability to metastasize.  The scientists reported that reducing N-cadherin expression in pancreatic cancer cells could delay tumor progression and prolongs survival by 25% in mouse model.

N-Cadherin is commonly found in cancer cells and has been associated with transendothelial migration. When a cancer cell adheres to the endothelial cells of a blood vessel it up-regulates the src kinase pathway, which phosphorylates beta-catenins attached to both N-cadherin and E-cadherins. This causes the intercellular connection between two adjacent endothelial cells to fail and allows the cancer cell to pass.

“Previous studies demonstrated the importance of this cell surface protein for tumor cell growth,” said Glenn Radice, the lead investigator of the study,  “However, it was not clear from those studies whether interfering with N-cadherin levels would increase survival of animals genetically engineered to develop highly metastatic pancreatic cancer.”

“Our survival results are very exciting because a drug, known as ADH-1, that specifically targets N-cadherin is already in clinical trial for melanoma. The next step is to test this N-cadherin-function blocking drug or a similar compound in the pancreatic cancer mouse model to see if it can prolong survival,” added Glenn Radice.

The discovery can potentially be used as a new targeted therapies for pancreatic cancer that may eventually be tested in clinical trials.

Novartis and collaborators discovered a new class of experimental antimalaria drugs. The dual-acting antimalarial compounds, known as imidazolopiperazines could potentially fight the scourge of malaria, advancing the search for treatments to replace current medicines as they lose potency against the infectious killer.

The study,  published online by the journal Science today, showed the novel class drugs attack parasites that cause malaria earlier than currently approved therapies. The compounds target both liver and blood infections, attacking the Plasmodium parasite at both stages in its reproduction cycle. which means they may be useful both for treating malaria and protecting against it.

Malaria kills a child in Africa every 45 seconds, according to the World Health Organization. It infects about 225 million people each year and causes more than 780,000 deaths, making it the world’s third-deadliest infectious disease behind AIDS and tuberculosis. 

Paul Herrling, head of corporate research at Novartis, said the the new drugs work in a different way than existing medicines, meaning they’ll “probably be active on all resistant strains of malaria that we know, and even on potential resistant strains to artemisinins.”

“For over a decade, Novartis has engaged in the front ranks of combating malaria, pioneering the not-for-profit supply of our antimalarial treatment Coartem to the public sector of endemic countries,” commented Joseph Jimenez, CEO of Novartis. “These new findings further demonstrate our innovative and sustainable research commitment in this important area which has become integral to our corporate strategy for social responsibility.”

This is the second new class of antimalarials discovered by the same group in the last two years and holds promise as a next-generation treatment for malaria if confirmed.

“Compounds with dual activity are rare among current antimalarials,” said Martin Seidel, GNF Institute Director. “The activity of the IZP compound class on liver-stage parasites, if it can be confirmed in clinical trials, gives promise to this class as a first-line therapy for the prevention and treatment of malaria.”

Researchers at MIT have discovered a promising new drug that appears to be able to hunt down and terminate cells infected with a virus, potentially providing a novel treatment for ranges of viral infections.

The research of a group of scientists from MIT was published in the online journal  PLoS One recently. This novel approach is partially based on how the human immune system takes down viruses. When a virus infects a cell in a human or an animal, it uses the machinery of that cell to reproduce, as viruses can’t reproduce on their own. During the reproduction process, the virus causes the creation of long chains of double-stranded RNA (dsRNA), which doesn’t naturally exist in either human or animal cells. When infected by a virus, the immune system typically targets those chains of dsRNA in an attempt to prevent replication.

Researhcer from the Lincoln Laboratory  have engineered proteins named DRACOs (Double-stranded RNA-Activated Caspase Oligomerisers) that will get into cells, bind to double-stranded RNA, and activate caspases when two or more of them stick to the same molecule. The double-stranded RNA in normal cells, unlike the RNA produced by viruses, is too short to accommodate two DRACOs. So only infected cells will be killed.

Todd Rider, a senior scientist in Lincoln Laboratory, and his colleagues showed that DRACOs work well in laboratory tests using cells in culture infected with many different viruses, including those that cause the common cold and dengue fever. They also work against influenza in mice.

“In theory, it should work against all viruses,” says Todd Rider. Their tests worked on rhinoviruses that cause the common cold as well as H1N1 and polio. And the technology could make it effective against lethal new viruses that pop up unexpectedly, similar to the SARS outbreak.

An article from The New York Times by Dan Hurley tells the story of Alberto Costa, a neuroscientist inspired by the birth of a daughter with Down syndrome to seek a treatment for the genetic disorder.

Alberto Costa is engaged in a randomized human trial for a potential new therapyAfter 15 years of investigation , reported the article. Working with a mouse model of the disease, Costa studied the positive effects of memantine, an Alzheimer’s drug, on the affliction. Because Down syndrome patients have three copies of the hundreds of genes found on Chromosome 21, Costa theorized that the drug worked because it quieted down an over-stimulated neurotransmitter. The NMDA transmitters in the mice model had become hyperactive, he theorized, and malfunctioned.

Other drug development strategies for Down syndrome which have shown promise include clearing excess amounts of beta amyloid, a protein which builds up in the brains of Alzheimer’s patients. And researchers’ work has captured the attention of biotech companies interested in pushing a drug through the clinical trial process.

“There’s been a sea change in our ability to understand and treat Down syndrome,” UC San Diego’s Dr. William C. Mobley, one of the most prominent scientists in the field, tells The Times. “There’s just been an explosion of information. As recently as the year 2000, no drug company would possibly have thought about developing therapies for Down syndrome. I am now in contact with no less than four companies that are pursuing treatments.”

But some, including Costa, believe that new tests that will make it quite simple to spot Down syndrome in fetuses will make future cases rare.

Natural IGF-II strengthens memory in rats

Scientists have revealed a key chemical that boosts memory, raising hope for new approaches to treat Alzheimer’s.

Published  in Nature, investigators of Mount Sinai School of Medicine, New York have shown that the Insulin-like growth factor 2  (IGF-II) plays a key role in the laying down and the strengthening of memories, pointing the way to a potentially effective treatment for dementia.

IGF-II, one of three protein hormones that share structural similarity to insulin,  significantly boosted retention and prevented forgetting of a fear memory when injected into rats’ memory circuitry during time-limited windows when memories become fragile and changeable. Animals treated with IGF-II excelled at remembering to avoid a location where they had previously experienced a mild shock.
The protein occurs naturally in the body, and is found in relatively high levels in the hippocampus, the brain’s memory hub.  However, levels decline with age.

Professor Cristina Alberini and colleagues from Mount Sinai say that they were able to either improve their memory with the molecule or make it worse by inhibiting IGF-II. As the molecule already occurs naturally in the brain, and can cross the blood-brain barrier, the researchers hope that they can translate their work in rats to humans, where dementia remains one of the highest unmet medical needs in drug development today.

“The implications of these data are far-reaching and give us new clues about how to investigate memory loss and forgetfulness in people with cognitive impairment, like those with Alzheimer’s disease, stroke or dementia,”  said Professor Alberini, “This study is the first step to understanding the benefits of IGF-II.  We have identified some of the mechanisms associated with this effect and look forward to studying them further and exploring the clinical relevance of IGF-II.”

Arachidonic acid and prostate cancer

Scientists from Finland have identified four metabolic enzymes regulating prostate cancer cell growth, which may potentially be used as drug targets for prostate cancer treatment.

In a paper published in The American Journal of Pathology in February 2011, researchers from VTT Technical Research Centre of Finland and the University of Turku reported the discovery of  four metabolic enzymes that regulate arachidonic acid metabolism and prostate cancer cell growth. In cultured cells, suppresion of the activity of these enzymes prevents prostate cancer cell growth . This discovery may be used to identify different subtypes of prostate cancer and for designing targeted therapies for prostate cancer.

Arachidonic acid metabolism produce  eicosanoid hormones, which are essential regulators of normal bodily functions. Metabolic dysfunction relating to these bioactive lipids plays a role in many diseases. It was found that prostate cancer cells use increased arachidonic acid metabolism and eicosanoid production to fuel their enhanced growth.

The scientists analysed the prevalence of enzymes involved in arachidonic acid metabolism in hundreds of prostate cancer samples, normal prostate samples, and other healthy tissues in this study. The enzymes with the highest expression in prostate cancer samples were selected for further studies in prostate cancer cells.  Certain enzymes were more prevalent than others in different kinds of prostate cancers. This knowledge can be used to identify different subtypes of prostate cancer in the future. The findings of the study provide valuable new information and can potentially lead to the discovery of new ways to treat prostate cancer.