Scientists Maybe Close to Finding a Cure for Asthma

LOS ANGELES, CA – Scientists led by molecular immunologists at the Keck School of Medicine of the University of Southern California (USC) have identified a way to target a recently discovered cell type that causes asthma, paving the way to cure the chronic respiratory disease that affects 25 million Americans.

The team, which includes investigators from Janssen Research and Development, Dana-Farber Cancer Institute and Harvard Medical School, recently published its results in the peer-reviewed scientific journal Immunity.

University of South Carolina

Asthma is a chronic lung disease that irritates and narrows the airways, according to the Centers for Disease Control and Prevention. With no known cure for the 7 million children who suffer from this disease in the United States, as well as millions of adults, the goal of asthma treatment is to control the symptoms. The exact causes of this chronic disease are unknown, but researchers believe a combination of genetic and environmental factors contribute to developing asthma. Discovered within the last decade, type 2 innate lymphoid cells, or ILC2s, are a subset of immune cells that trigger primary asthma symptoms such as mucus production and hypersensitive airways. ILC2s do not express previously identified immune cell markers, however, making them tough to target.

“If we can target ILC2s, we might be able to cure asthma or exacerbations caused by these particular cells,” said Omid Akbari, Ph.D., associate professor of molecular and cellular immunology at the Keck School of Medicine of USC and principal investigator of the study. “In this study, we discovered molecules critical to ILC2 homeostasis, survival and function. We believe that targeting these molecules or related pathways could one day cure a patient with ILC2-dependent asthma.”

Akbari’s team used mouse and human cells to show that inducible T cell costimulator molecules (ICOS) and their interaction with ICOS-ligand (ICOS-L) are crucial for ILC2 function and survival. ICOS and ICOS-L are proteins that influence cell behavior and cell response. Akbari’s team developed a humanized mouse model to show how human ILC2s function in vivo; the model is currently being used to study how ILC2s contribute to human asthma and test potential therapies in preclinical studies.

“Because ILC2s are the only cells that express both ICOS and ICOS-L, our research sets the stage for designing new therapeutic approaches that target ILC2s to treat asthma,” said Hadi Maazi, D.V.M., Ph.D., a research associate in Akbari’s lab and the study’s first author.

- MFPNews Services
- 4/17/15

No Apparent Link Found Between Sleep Apnea and Cancer

TORONTO, Ont. – Obstructive sleep apnea, in which people stop breathing for short periods while sleeping, affects about 5% of Canadian adults aged 45 years or older and can negatively affect health. More than 1 in 5 adult Canadians have risk factors for sleep apnea such as being overweight, being male and having diabetes, chronic nasal congestion or other health conditions.

Studies have postulated that obstructive sleep apnea may be linked to cancer because of low levels of oxygen in the blood.

“There is a need for a sufficiently large cohort study with a long enough follow-up to allow for the potential development of cancer that adjusts for important potential confounders, examines common cancer subtypes and has a rigorous assessment of both obstructive sleep apnea and cancer,” writes Dr. Tetyana Kendzerska, Institute for Clinical Evaluative Sciences (ICES) and Women’s College Hospital, University of Toronto, Toronto, Ont., with coauthors.

WCH ON

To understand whether obstructive sleep apnea is associated with cancer development, researchers undertook a study of 10 149 patients with the disorder who underwent a sleep study between 1994 and 2010. They linked this information to health administrative databases from 1991 to 2013. At the start of the study, 520 (5.1%) had a cancer diagnosis. In the study follow-up period (median 7.8 years), 627 (6.5%) people who did not have cancer at baseline had incident cancer. Prostate, breast, colorectal and lung cancers were the most common.

After controlling for cancer risk factors, the researchers found no apparent causal link between obstructive sleep apnea and cancer.

“We were not able to confirm previous hypotheses that obstructive sleep apnea is a cause of overall cancer development through intermittent hypoxemia [low blood oxygen levels],” write the authors. “However, in subgroup analyses, we found that the level of oxygen desaturation was associated with the development of smoking-related cancer.”

- MFPNews Services
- 4/15/2015

Drug Target Identified For Common Childhood Cancer

NEW YORK, NY – In what is believed to be the largest genetic analysis of what triggers and propels progression of tumor growth in a common childhood blood cancer, researchers at NYU Langone Medical Center report that they have identified a possible new drug target for treating the disease.

T-cell acute lymphoblastic leukemia is one of the most common and aggressive childhood blood cancers. An estimated quarter of the 500 adolescents and young adults diagnosed with the cancer each year in the U.S. fail to achieve remission with standard chemotherapy drugs.

NYU Langone Medical Center

In a cover-story reported in the journal Cell online, the NYU Langone team describes how they used advanced genetic scanning techniques to identify 6,023 so-called long, non-coding strands of RNA, vital chemical cousins of DNA, that were active in the immune system T cells taken from 15 boys and girls with T-cell acute lymphoblastic leukemia, but not active in the healthy T cells in three young people without the disease.

Further analysis found that chemically blocking the action of one of those non-protein-producing RNAs, known as leukemia-induced non-coding activator RNA-1, or LUNAR1 for short, stalled leukemia progression.

Study investigators say LUNAR1 was not singled out from RNA typically used by DNA to make proteins, but rather from among the most prevalent RNA — long chemical strands of translated DNA, previously termed “junk DNA” — which can help transcribe DNA but never fully assemble proteins. They say these long non-coding RNAs are increasingly recognized as key to regulating many cell functions.

Senior study investigator and NYU Langone cancer biologist Iannis Aifantis, PhD, says the study offers preliminary evidence that drugs blocking LUNAR1 could treat T-cell acute lymphoblastic leukemia and a long-sought alternative to chemotherapeutic drugs that kill both cancer and normal cells.

Aifantis, a professor and chair of pathology at the Laura and Isaac Perlmutter Cancer Center at NYU Langone, and an early career scientist at the Howard Hughes Medical Institute, also says LUNAR1 could aid in diagnosing the blood cancer.

“Our study shows that LUNAR1 is highly specific for T-cell acute lymphoblastic leukemia and plays a key role in how this cancer develops,” he says, pointing out that overproduction of LUNAR1 was recorded in almost all (90 percent) of leukemia patients tested.

Moreover, Aifantis says, his team’s latest findings suggest that development of future cancer therapies based on the underlying genetics of each patient should involve “not just mutations in someone’s DNA, but also alterations in the makeup of RNA.”

Among the study’s other key findings was that while LUNAR1 does not produce cancerous proteins on its own, its production was essential to the cell-to-cell signaling action of another protein, insulin-like growth factor 1 receptor (IGF-1R), already tied to many cancers, including leukemia.

Further laboratory experiments showed that the gene coding for LUNAR1 is near the gene for IGF-1R and located toward the chromosomes’ ends, known as telomeres. When activated, LUNAR1′s position allows it to chemically loop back and, in turn, bind to and activate IGF-1R.

Researchers zeroed in on LUNAR1 by pinpointing those RNAs that also were active in the NOTCH1 biological pathway. They say the NOTCH1 pathway is common to many cancers, but is especially active in at least half of all people with T-cell acute lymphoblastic leukemia. LUNAR1 stood out right away, they say, as the most highly expressed long, non-coding RNA, of which more than half were newly discovered.

According to Aifantis, his team’s research shows that T-cell acute lymphoblastic leukemia, as is the case in many other cancers, could be simply described as a condition of “too much errant signaling.” He says in normal T cells, the long, non-coding RNAs such as LUNAR1 are not transcribed, NOTCH1 is inactive, and there is no looping back of LUNAR1 to activate IGF-1R.

To confirm their findings, researchers also transplanted human leukemia T cells into mice to prompt tumor growth, and chemically blocked LUNAR1 in some of the animals. Tumor growth stalled only in those mice whose LUNAR1 was inactivated.

Aifantis says his team’s next steps are to develop more effective inhibitors of LUNAR1, preferably something that would precisely target any one or more of its 200-plus component nucleotides.

- MFP NEWS SERVICES
- 4/14/2015