03 Jan Nanoparticles May Enable Delivery of Drugs Across Blood Brain Barrier
MedicalResearch.com Interview with: [caption id="attachment_56348" align="alignleft" width="100"]
Dr. Joshi[/caption]
Nitin Joshi, Ph.D.
Engineering in Medicine/Department of Medicine
Brigham and Women's Hospital
[caption id="attachment_56349" align="alignleft" width="100"] Dr. Karp[/caption]
Dr. Jeffrey M Karp Ph.D
Principal Investigator
Professor of Medicine at Brigham and Women’s Hospital
Harvard Medical School
MedicalResearch.com: What is the background for this study? Would you explain what is meant by the blood brain barrier? How will nanoparticles facilitate transport of drugs into the brain?
Response: Over the past few decades, researchers have identified promising therapeutic agents that can target the biological pathways involved in brain diseases. Unfortunately, clinical translation of these therapeutics is limited by their inability to cross the blood brain barrier (BBB) and enter the brain at therapeutically effective levels. The BBB is a highly selective semipermeable border of cells that prevents molecules in the circulating blood from non-selectively crossing into the brain tissue. We have developed a simple targeted nanoparticle platform that can stably encapsulate therapeutic agents and enable their therapeutically effective delivery into the brain. In this work, we have demonstrated the utility of this platform for the treatment of traumatic brain injury (TBI), which is a leading cause of death and disability in children and young adults, with millions of people suffering TBI each year in accidents, sports, and military conflicts. Following primary injury, which is a result of the mechanical impact to the brain, secondary injury gradually occurs over months to years and can lead to neurological dysfunctions, including Alzheimer’s and Parkinson’s diseases.
After TBI, the BBB is physically breached for a short time and previous approaches to achieve therapeutically effective transport of drugs across the BBB have been severely limited to utilizing this very short window. However, the extent to which the BBB is physically breached in TBI varies greatly across the patient population. Therefore, current approaches are applicable to only a subset of injuries with substantially breached BBB. Moreover, BBB can self-repair within a few hours to weeks post-injury to restore its integrity. Hence, physical breaching of BBB offers a limited window for therapeutic interventions, which is not ideal as the secondary injury can last months to years and may require repeated dosing over long term.
The nanoparticle platform developed in this work can enable therapeutically effective delivery of drugs into the brain, irrespective of the state of the BBB. We achieved this by precise engineering of the surface properties of nanoparticles, which maximized their transport across the BBB. The therapeutic used in this study was a small interfering RNA (siRNA) molecule designed to inhibit the expression of the tau protein, which is believed to play a key role in neurodegeneration. Poly(lactic-co-glycolic acid), or PLGA, a biodegradable and biocompatible polymer used in several existing products approved by the U.S. Food and Drug Administration was used as the base material for nanoparticles. We systematically engineered and studied the surface properties of the nanoparticles to maximize their penetration across the intact, undamaged BBB in healthy mice. This led to the identification of a unique nanoparticle design that maximized the transport of the encapsulated siRNA across the intact BBB and also significantly improved the uptake by the brain cells.
Dr. McGahan[/caption]
Anita M. McGahan PhD, MBA
University Professor
Professor of Strategic Management
Professor, Munk School of Global Affairs & Public Policy
George E. Connell Chair in Organizations & Society
Rotman School of Management
University of Toronto
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The article by Phebo Wibbens, Wesley Wu-Yi Koo, and me that came out today in PLOS ONE at 
Dongmei Li, Ph.D.[/caption]
Dongmei Li, Ph.D., Associate Professor
Clinical and Translational Science Institute
University of Rochester Medical Center
MedicalResearch.com: What is the background for this study?
Response: Previous animal and human studies have found that nicotine exposure could harm adolescents’ brain development and impact their cognitive functions. Electronic cigarettes, which have become very popular among youth in the US in recent years, usually contain nicotine at equivalent or possibly higher levels than traditional tobacco cigarettes. Thus, it is reasonable to assume that vaping might be associated with self-reported cognitive complaints.
MedicalResearch.com: What are the main findings?
Response: Main findings from our study are:
Dr. Li[/caption]
Li Li, MS, PhD Candidate
Division of Epidemiology, College of Public Health, Ohio State University
Graduate Research Associate, Center for Injury Research and Policy
The Abigail Wexner Research Institute at Nationwide Children’s Hospital
MedicalResearch.com: What is the background for this study?
Response: Marijuana use impairs cognitive abilities necessary for safe driving, including reaction time, road lane-tracking ability, and attention maintenance. Given increasing legalization of marijuana use in the US, our study aimed to estimate marijuana-impaired driving among teens at a national level and help to identify the current prevalence to guide future intervention programs. 
Rebecca McNally[/caption]
Rebecca McAdams, MA, MPH
Senior research associate
Center for Injury Research and Policy
Nationwide Children’s Hospital
Columbus, OH
MedicalResearch.com: What is the background for this study?
Response: Sledding is a popular winter activity in communities across the country, but it may not be as risk-free as many people think.
MedicalResearch.com: What are the main findings?
Response: We found that 220,488 patients were treated in U.S. emergency departments for injuries related to sledding from 2008 through 2017. Nearly 70% of these patients were children age 19 years and younger. Compared to adults, children were almost seven times as likely to be treated in an emergency department for a sledding-related injury.
The majority of patients were injured as the result of a collision (63%). Collision injuries occurred when the patient made contact with an object in the environment (47%), when they hit the ground (16%), or when they ran into another person (10%) or sled (7%).
Head injuries are a serious concern during sledding. The head was the most frequently injured body part for children. In fact, nearly 82% of those who sustained an injury to the head were children. The type of sled can also impact the risk of head injury. Children injured while riding snow tubes and disks had a greater risk of sustaining a concussion or CHI than children who were riding sleds or toboggans. Researchers recommend wearing a helmet while sledding to reduce the risk and severity of head injuries.
While less frequent (3% of all cases), injuries occurring as a result of the sled being pulled by a motorized vehicle such as a car, ATV or snowmobile resulted in more serious injuries that required hospitalization (14%). This practice should be avoided. 
Dr. Aronne[/caption]
Dr. Louis Aronne, MD, FACP
Chief Medical Officer, Intellihealth
Medical Director, Comprehensive Weight Control Center
Weill Cornell Medicine
MedicalResearch.com: What is the background for the study “Effect of an Online Weight Management Program Integrated With Population Health Management on Weight Change: A Randomized Clinical Trial”?
Response: More than 70% of U.S. adults have overweight or obesity. Online programs promoting lifestyle change have had some success in helping people achieve and maintain weight loss, but study results have been variable, and these programs have not been widely implemented in primary care. We studied the effectiveness of an online program we have developed (Intellihealth, formerly known as BMIQ) in routine primary care practices, both alone and integrated with population health management (with participants receiving additional support and outreach from nonclinical staff). The study’s objective was to determine whether a combined intervention integrating online weight management with population health management would increase weight loss at 12 months among primary care patients compared with the online program only and usual care.
Dr. Magnusson[/caption]
Karin Magnusson PT, PhD
Associate Researcher
Lund University and
Norwegian Institute of Public Health
MedicalResearch.com: What is the background for this study?
Response: Anterior cruciate ligament (ACL) injury is one of the most common knee injuries, for which very limited data has been presented on the genetic contribution. Based on our knowledge of the role of genetics in the development of ACL-rupture related traits, such as joint hypermobility and knee osteoarthritis, we hypothesized that heritability might play a role also in ACL injury.
Using the Swedish Twin Registry, which is the world's largest twin registry and in this study including more than 88.000 twins, we had unique data to for the first time reliably estimate the heritability for this common knee injury. 
Dr. Chua[/caption]
Isaac Chua, MD, MPH
Division of General Internal Medicine and Primary Care
Brigham and Women's Hospital
MedicalResearch.com: What is the background for this study?
Response: Patient surveys have shown that most people prefer to die at home at the end-of-life. However, during the initial wave of the COVID-19 pandemic, anecdotal evidence from our colleagues and findings from a prior study published in the Journal of the American Geriatrics Society suggested that majority of COVID-19 decedents died in a medical facility. However, less is known about care intensity at the end-of-life according to place of death among patients who died of COVID-19. Therefore, we characterized end-of-life care by place of death among COVID-19 decedents at Mass General Brigham (MGB), the largest health system in Massachusetts. 
Dr. Maru[/caption]
Sheela Maru, MD, MPH
Department of Health System Design and Global Health and
Arnhold Institute for Global Health and
Department of Obstetrics, Gynecology and Reproductive Science
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study?
Response: Universal screening for SARS-CoV-2 infection on Labor and Delivery (L&D) units is a critical strategy to manage patient and health worker safety, especially in a vulnerable high-prevalence community. We describe the results of a SARS-CoV-2 universal screening program at the L&D Unit at Elmhurst Hospital in Queens, NY, a 545-bed public hospital serving a diverse, largely immigrant and low-income patient population and an epicenter of the global pandemic.
