Syndicate content

Archive - Aug 7, 2017

Yale Scientists Reveal Role for Lysosome Transport in Alzheimer's Disease Progression; Finding Suggests Possible New Therapeutic Approaches

Researchers from the Yale University School of Medicine have discovered that defects in the transport of lysosomes within neurons promote the buildup of protein aggregates in the brains of mice with Alzheimer's disease. The study, which was published on August 7, 201 in The Journal of Cell Biology (JCB), suggests that developing ways to restore lysosome transport could represent a new therapeutic approach to treating the neurodegenerative disorder. The open-access article is titled “Impaired JIP3-Dependent Axonal Lysosome Transport Promotes Amyloid Plaque Pathology.” Alzheimer's disease is the sixth leading cause of death in the United States, with over 5 million Americans currently estimated to be living with the disorder. A characteristic feature of the disease is the formation of amyloid plaques inside the brain. The plaques consist of extracellular aggregates of a toxic protein fragment called β-amyloid surrounded by numerous swollen axons, the parts of neurons that conduct electric impulses to other nerve cells. These axonal swellings are packed with lysosomes, cellular garbage disposal units that degrade old or damaged components of the cell. In neurons, lysosomes are thought to "mature" as they are transported from the ends of axons to the neuronal cell body, gradually acquiring the ability to degrade their cargo. The lysosomes that get stuck and accumulate inside the axonal swellings associated with amyloid plaques fail to properly mature, but how these lysosomes contribute to the development of Alzheimer's disease is unclear. One possibility is that they promote the buildup of β-amyloid because some of the enzymes that generate β-amyloid by cleaving a protein called amyloid precursor protein (APP) accumulate in the swellings with the immature lysosomes.

Scientists Create Potential Stem Cell Therapy for Lung Fibrosis Conditions, Including Idiopathic Pulmonary Fibrosis (IPF)

A team of scientists from the University of North Carolina (UNC) School of Medicine and North Carolina State University (NCSU) has developed promising research towards a possible stem cell treatment for several lung conditions, such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and cystic fibrosis -- often-fatal conditions that affect tens of millions of Americans. In the journal Respiratory Research, the scientists demonstrated that they could harvest lung stem cells from people using a relatively non-invasive, doctor's-office technique. They were then able to multiply the harvested lung cells in the lab to yield enough cells sufficient for human therapy. Thus open-access article, published online on June 30, 2017, is titled “Derivation of Therapeutic Lung Spheroid Cells from Minimally Invasive Transbronchial Pulmonary Biopsies.” In a second study, published in Stem Cells Translational Medicine, the team showed that in rodents they could use the same type of lung cell to successfully treat a model of IPF - a chronic, irreversible, and ultimately fatal disease characterized by a progressive decline in lung function. The open-access article, published online on August 7, 2017, is titled “Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis.” The researchers have been in discussions with the FDA and are preparing an application for an initial clinical trial in patients with IPF. "This is the first time anyone has generated potentially therapeutic lung stem cells from minimally invasive biopsy specimens," said co-senior author of both papers Jason Lobo, MD, an Assistant Professor of Medicine at UNC and Medical Director of Lung Transplant and Interstitial Lung Disease.

Using CRISPR and Skin Grafts, Researchers Boost Insulin Levels to Correct Diet-Induced Obesity and Diabetes in Mice; Gene Therapy Via Skin Could Treat Many Diseases, Scientists Suggest

A research team based at the University of Chicago has overcome challenges that have limited gene therapy and demonstrated how their novel approach with skin transplantation could enable a wide range of gene-based therapies to treat many human diseases. In the August 3, 2017 issue of Cell Stem Cell, the researchers provide "proof-of-concept." They describe a new form of gene-therapy - administered through skin transplants - to treat two related and extremely common human ailments: type-2 diabetes and obesity. "We resolved some technical hurdles and designed a mouse-to-mouse skin transplantation model in animals with intact immune systems," said study author Xiaoyang Wu, PhD, Assistant Professor in the Ben May Department for Cancer Research at the University of Chicago. "We think this platform has the potential to lead to safe and durable gene therapy, in mice and we hope, someday, in humans, using selected and modified cells from skin." Beginning in the 1970s, physicians learned how to harvest skin stem cells from a patient with extensive burn wounds, grow them in the laboratory, then apply the lab-grown tissue to close and protect a patient's wounds. This approach is now standard. However, the application of skin transplants is better developed in humans than in mice. "The mouse system is less mature," Dr. Wu said. "It took us a few years to optimize our 3D skin organoid culture system." This study, entitled "Engineered Epidermal Progenitor Cells Can Correct Diet-Induced Obesity and Diabetes," is the first to show that an engineered skin graft can survive long term in wild-type mice with intact immune systems. "We have a better than 80 percent success rate with skin transplantation," Dr. Wu said. "This is exciting for us." The article is open-access.