Insights & Outcomes: Exosomes, a drug-coated balloon, and new info on AMOC
This month, Insights & Outcomes gets into the flow of Yale research — from the movement of RNA within the human body to the circulation of water in the Atlantic Ocean.
Exosomes to the rescue
Scientists have emphasized that engineering artificial nanoparticles is the best way to deliver potential therapeutic genetic information into cells. However, in a recently published essay, Yale immunologist Dr. Philip Askenase argues that a better therapeutic vehicle has existed since the dawn of evolution. Exosomes are natural, tiny lipid sacs that act like couriers, ferrying tiny sequences of RNA called microRNA to and from cells throughout the body. They are secreted by all cells in all animals. Once they enter the recipient cell, they are able to alter the behavior of genes that carry out life’s functions. Exosomes have many advantages over artificial nanoparticles as potential therapeutics, Askenase said. They are naturally able to pass through the blood-brain barrier, are not targeted by the immune system, and are extremely hardy, with a long evolutionary heritage. Exosomes have great value in developing targeted gene therapies to treat a host of diseases, Askenase said. The essay appears June 18 in the journal Nature Outlook.
Running the AMOC numbers
Climate scientists are drawing ever closer to understanding the effects of a warming climate on the Atlantic meridional overturning circulation (AMOC) — the Atlantic Ocean’s main water circulation system. AMOC operates like a conveyor belt, bringing warm water to the North Atlantic via an upper limb and sending colder water south via a deeper limb. Over the past 15 years, there have been signs that AMOC is slowing down, and an area of cooler, non-warming water has developed in the North Atlantic. A new study suggests that this “hole” of non-warming water may be linked to climate change and a slowing AMOC. “We have developed a new method to isolate the climatic impacts of the weakening AMOC,” said Yale professor of geology and geophysics Alexey Fedorov, co-author of the new study. “We compare our global warming simulations of a constant AMOC with simulations that have a declining AMOC.” Fedorov said when there is an active AMOC system in place, the non-warming hole in the North Atlantic disappears. The first author of the study is former Yale postdoctoral associate Wei Liu, who is now at the University of California-Riverside. The study appears in Science Advances.
A new way to study the brain
The brain is a particularly difficult and complex organ to study, but it has become more accessible thanks to a new technique developed by Yale neuroscientists. Researchers often use recombinant viruses to replace or alter genes in animals in order to study the genes’ effects on the development of diseases. However, it is quite expensive, and it often takes years to develop strains of genetically modified animals. The introduction of recombinant viruses into the brains of animals has also proven to be difficult and inefficient, making it unsuitable to study early genetic origins of autism, epilepsy, and schizophrenia, for instance. A Yale team led by Ali Hamodi, a postdoctoral fellow in neuroscience, developed a new method that eliminates these obstacles. When injected into a newborn rodent’s brain blood vessel known as the “transverse sinus,” the recombinant virus immediately allows researchers to study the effects of genes throughout the entire brain. “It enables you to create genetically modified animals, without the time, effort, and cost spent breeding genetically modified animals,” Hamodi said. The study appears in the journal eLife.
Grant will expand Yale’s addiction fellowship programs
The Health Resources and Services Administration (HRSA) has awarded a $2.5 million, five-year grant to expand Yale’s Addiction Medicine and Addiction Psychiatry Fellowship Programs. The grant will allow Yale School of Medicine to increase the number of board-eligible Addiction Medicine and Addiction Psychiatry fellows who graduate from Yale’s addiction-training programs each year, expand relationships with community treatment facilities, and further develop and recruit faculty clinician educators. “There are still shortages of physicians trained to treat addictive disorders,” said Dr. Ismene Petrakis, professor of psychiatry at Yale and chief of psychiatry at the VA Connecticut Healthcare system. “Those shortages particularly affect underserved populations. This grant will allow us to increase the number of trainees, prioritize placements in community programs, and encourage physicians to pursue careers in addiction treatment within community settings.” Dr. Jeanette Tetrault, associate professor of medicine (general medicine) and associate director for training and education for the Program in Addiction Medicine, directs the Addiction Medicine Fellowship. “With resources from HRSA, we can markedly expand our reach,” she said. “Additionally, by training fellows in community settings, we will prepare fellows to work where treatment is needed most.” The grant builds on collaborative efforts of Yale Medicine and Yale Psychiatry to treat addiction holistically, working closely with community partners such as Connecticut Mental Health Center, the APT Foundation, and federally qualified health centers. Special emphasis will be placed on training in telehealth services.
A plan for primary health care improvements in China
Although health care reform in China has pumped additional money into that country’s primary health care system and led to improvements in health care policies, medical researchers say wide gaps in the quality of primary health care still exist. Yale’s Dr. Harlan Krumholz, the Harold H. Hines Jr. Professor of Medicine (cardiology) and Public Health, and director of the Center for Outcomes Research and Evaluation, is co-lead author of a new review that offers sweeping recommendations to raise the quality of primary health care in China. Among the recommendations are better training and education of medical workers, integration of clinical care and public health services, the establishment of performance standards and accountability, and more active use of digital platforms for quality control and training. The article appears in The Lancet.
Here’s a preferential PAD treatment
Peripheral artery disease (PAD), the progressive narrowing of blood vessels away from the heart or brain that reduces blood flow to the limbs, affects more than 8.5 million Americans. The femoropopliteal artery, located in the leg, is a common site for PAD — and doctors currently have several endovascular options for treatment. A new, Yale-led review of those treatment options suggests that one is most preferable: a drug-coated balloon that is inserted in the leg, advanced to the narrowed area, and inflated. The authors, led by associate professor of medicine (cardiology) Dr. Carlos Mana-Hurtado, noted the safety profile, ease of use, and clinical efficacy of the drug-coated balloon procedure. The study appears in Expert Review of Medical Devices.