During the COVID-19 pandemic, Johns Hopkins Medicine Media Relations is focused on disseminating current, accurate and useful information to the public via the media. As part of that effort, we are distributing our “COVID-19 Tip Sheet: Story Ideas from Johns Hopkins” every other Tuesday.
We also want you to continue having access to the latest Johns Hopkins Medicine research achievements and clinical advances, so we are issuing a second tip sheet covering topics not related to COVID-19 or the SARS-CoV-2 virus. “Research News Tip Sheet: Story Ideas from Johns Hopkins Medicine” alternates Tuesdays with the COVID-19 Tip Sheet.
Stories in this tip sheet associated with journal publications provide a link to the paper. Interviews with the researchers featured may be arranged by contacting the media representatives listed.
SCIENTISTS CREATE MAP OF GATEKEEPER THAT COULD HELP BRAIN CELLS SURVIVE STROKE
VIDEO: Scientists Create Map of Gatekeeper That Could Help Brain Cells Survive Stroke
Researchers at Johns Hopkins Medicine have revealed the structure of a gatekeeping protein that could one day impact the treatment of conditions such as heart attack and stroke. Understanding the structure of the protein — known as the proton-activated chloride channel (PAC) — helps researchers develop ways to reduce permanent damage caused by conditions associated with acidosis, a condition marked by increased acidity in the blood.
“Knowing the structure of the PAC helps us understand how this acid-sensing protein works in different pH [the measure of acidity or basicity of a solution] and gives us potential ways to manipulate it for better medical outcomes,” says Zhaozhu Qiu, Ph.D., assistant professor of physiology at the Johns Hopkins University School of Medicine and co-corresponding author of the study.
The PAC protein is activated when the environment around the cell becomes acidic. Typically, acidity in the body is held at normal levels through constant blood flow. However, when the circulatory system is disrupted by heart disease, stroke or some cancers, the area quickly becomes acidic as cellular waste builds up.
The Johns Hopkins Medicine-led research team first reported the gene sequences encoding this new “acid sensor” in Science last year. In the study, the researchers showed that stroke can over-activate PAC and kill brain cells in mice.
For the current study, Qiu’s team worked with collaborators, led by Wei Lü, Ph.D., assistant professor of structural biology at the Van Andel Institute and co-corresponding author of the study, to collect two types of images of the PAC. One was taken in the protein’s relaxed state — at a cell’s normal biological acidity level — and the other in its active state, when the environment is highly acidic.
To create an accurate picture, they used the specialized, high-powered cryo-electron microscope that supercools molecules so they form precise, easily imaged structures at sizes nearly to the atomic level. The images showed that the PAC resembles a wedding bouquet, with parts that move in response to acidic pH. The movement links to the opening of the gate that enables chloride ions to flow in and out of the cell.
“The PAC structures are beautiful! Combined with functional studies, we revealed a completely new acid-sensing mechanism,” says James Osei-Owusu, a doctoral student in Qiu’s lab and co-first author of the study. “It sets an example for why getting a structure of the protein is really important and provides a blueprint of how the tiny molecular machine works.”
The researchers plan to conduct further studies to test the protein-activated channel’s sensitivity to acidic environments and screen for drugs that inhibit the chloride movement through it.
“PAC is widely distributed in many tissues,” says Qiu. “Its function in healthy cells is still a big mystery. We hope to solve this puzzle in the near future.”
STUDY SHOWS JOHNS HOPKINS MEDICINE DEVICE SAFELY TREATS BRAIN SWELLING ‘UNDERCOVER’
It’s slightly shorter in length than a credit card and only as thick as a stack of seven pennies, but the medical device known as the valve-agnostic cranial implant (VACI) has proven large in its quality-of-life return for adult patients with hydrocephalus, a dangerous brain swelling. The team that created the VACI, led Johns Hopkins Medicine researchers, recently announced preliminary findings from a multicenter clinical trial that showed — when compared with traditional shunts used to remove the excess cerebrospinal fluid (CSF) associated with hydrocephalus — the device successfully treats the condition with fewer complications, enables easier maintenance and monitoring without follow-up surgery, and gives the patient a more normal appearance.
According to the National Institute of Neurological Disorders and Stroke, hydrocephalus is an abnormal buildup of CSF — the clear, colorless liquid that protects and cushions the brain — circulating in the brain’s cavities (ventricles). Hydrocephalus occurs when the normal flow and absorption of CSF is blocked, leaving the excess fluid to widen and swell the ventricles. This puts pressure on the brain and keeps it from properly functioning, leading in turn leading to neurological damage and, in severe cases, death.
Hydrocephalus is most commonly treated in adults by implanting a 1-inch-thick shunt device onto the skull and draining the excess CSF through a tube into either the chest cavity or abdomen, where the fluid is absorbed. However, the traditional shunt — a device that basically has not changed in design since its development over 60 years ago — has a high risk of complications, such as skin breakdown, infection and long-term scalp pain; typically requires multiple surgeries for repair or replacement throughout a patient’s lifetime; and forms a noticeable bump that many patients find aesthetically unpleasing.
“Our team knew there had to be a better solution, so we created the VACI, a pre-molded, computer-designed cranial implant that cradles a shunt invisibly within the 4 to 5 millimeters of skull space between the scalp and the brain,” says Chad Gordon, D.O., director of neuroplastic and reconstructive surgery, and professor of plastic and reconstructive surgery at the Johns Hopkins University School of Medicine. “The recent clinical trial was conducted by surgical teams at various institutions to determine if the VACI could improve patient safety and minimize the complications often seen with traditional shunts.”
In the trial, 25 adult patients with hydrocephalus — 14 women and 11 men ranging in age from 22 to 84 — were fitted with the VACI at four medical institutions. The patients were monitored for an average of 13 months with 23 (92%) reporting no major scalp or shunt-related complications. One patient experienced a scalp wound over a catheter away from the device and another developed a CSF infection. Neither of these complications were related to the VACI.
“Based on its successful performance, we believe that the VACI is a newfound weapon against neurosurgical-induced deformities, postoperative complications and suboptimal surgical outcomes when treating adult hydrocephalus,” says Gordon.
The VACI, now known by its trade name InvisiShunt, was first used in a patient in 2018. The device and the surgical procedure for its implantation are part of a new medical discipline being pioneered by Gordon and his Multidisciplinary Adult Cranioplasty Center team to use the cranial bone space — a field they have dubbed “neuroplastic and reconstructive surgery.”
The team’s other achievements include the first-ever cranial implants with: (1) closed-loop direct brain neurostimulators for treating epilepsy, and (2) a “smart” wireless biosensor for continuous monitoring of pressure inside the skull after bone removal to relieve traumatic swelling.
“Both eliminate the risks associated with placing bulky devices under the scalp, thereby making the procedures safer and better tolerated by our neurosurgical patients,” says Gordon.
Gordon is co-founder of Longeviti Neuro Solutions, which manufactures and markets the InvisiShunt under an arrangement approved by The Johns Hopkins University. Both Gordon and the university are entitled to royalty distributions for the technology. Two other authors, Judy Huang, M.D., and Erol Veznedaroglu, M.D., own stock in the company and serve as a paid consultant, respectively.
EPILEPSY AWARENESS MONTH TALE: CHLOE RESPONDS WELL TO JOHNS HOPKINS CHILDREN’S CENTER CARE
At the age of 2, Chloe Dela Cruz, of Lake Ridge, Virginia, was a spunky and outgoing child without any health concerns. But that changed just a few months before her third birthday, recalls her mother Joanne Dela Cruz, when a horrifying experience happened after the family participated in a fun run event.
“Everything was going fine, and I turned around and I saw my daughter seizing in her car seat,” Joanne says. “We didn’t know what was going on.”
Chloe’s parents rushed her to a local hospital. At first, her medical team thought the seizure was a febrile seizure — a condition associated with a fever. But Chloe’s seizures increased in frequency — happening three or four times per day — and her parents were eventually told that she had epilepsy.
November is National Epilepsy Awareness Month. According to the Epilepsy Foundation, the disease is a disorder of the brain that causes seizures, affects one in 26 people and is more frequently seen in children than other age groups. It is one of the most common reasons that children are seen by a pediatric neurologist. Because seizures vary in their causes and characteristics, epilepsy affects people in many different ways.
In Chloe’s case, Joanne says her arms would stiffen and her eyes would widen. She would make mouth-clicking noises and was not able to hear anyone around her. After some time, Chloe’s seizures turned into “drop” seizures, and she was diagnosed with myoclonic astatic epilepsy, also known as Doose syndrome.
“She would violently drop and fly backward with force,” Joanne recalls. “She was hurting herself.”
Chloe was fitted for a helmet to protect her head in case of a seizure. During a three-month period, she was in and out of the hospital multiple times. Chloe also started having seizures at night, and Joanne, who calls herself a “scared, worry momma,” started sleeping in Chloe’s room.
Throughout those months, Chloe tried six anti-seizure medications in various combinations. Joanne says the medications affected Chloe’s function and caused her to gain weight. The girl’s local doctors recommended lowering carbohydrates, similar to a modified Atkins diet. That helped, but the seizures continued.
Eventually, after a recommendation from a friend, Joanne, Chloe and the family were referred to Eric Kossoff, M.D., professor of neurology and pediatrics at the Johns Hopkins University School of Medicine and medical director of the Pediatric Ketogenic Diet Center. Shortly after Kossoff began caring for Chloe, he prescribed one of the oldest treatments for epilepsy: the stricter, classic ketogenic diet, which calls for eating high-fat foods and few carbohydrates.
Chloe was admitted to Johns Hopkins Children’s Center in February of this year as standard protocol for pediatric patients at the start of a ketogenic diet. Within one month, her seizures stopped. The need for two of her three anti-seizure medications ended by the summer, and she is now nearly off the last one.
As Chloe approaches her fourth birthday this month, she has been seizure-free for more than 200 days. Her mother says Chloe is doing “fantastic.”
“She is such a trooper,” Joanne says. “She is super smart, super sassy, very kind and loving.”
“Chloe is one our favorite keto patients to see in clinic,” Kossoff adds. “She always sends us drawings, and her mother emails great photographs showing how well she is doing.”
JOHNS HOPKINS MEDICINE CELEBRATES GENETIC COUNSELOR AWARENESS DAY ON NOV. 12
Genetic counselors are a special group of health care workers dedicated to helping patients and their families with genetic health education, advice and strategy planning. They provide medical and emotional support in a number of specialty areas — such as pediatrics, prenatal care and personalized medicine — and for medical conditions, including sickle cell anemia, obesity and cancer.
Genetic Counselor Awareness Day is Nov. 12, and Johns Hopkins Medicine is marking the occasion by helping the public become familiar with what genetic counselors do and how they can help.
Here are 10 facts that everyone should know about genetic counseling and genetic health:
- Genetic counselors can help you understand inherited conditions that could affect your health, the best options for genetic testing, and how your medical and family history can guide your health plans.
- Genetic counselors serve in many places, including direct patient care settings, research facilities, public policy institutions, patient advocacy organizations and medical education groups.
- Consider seeing a genetic counselor if:
- You or a family member have a birth defect, inherited condition or learning problem,
- You are pregnant or planning a pregnancy, and want to learn more about prenatal screening, had an unexpected ultrasound finding or experienced a miscarriage,
- More than one relative on the same side of the family has had cancer before age 50 or were diagnosed with a rare cancer type.
- A genetic counselor can use your family history information to help determine if you might be at risk for hereditary conditions and, if so, what medical care your doctor should recommend to deal with them.
- Counselors can help record your family’s genetic history and make sure it includes as many blood relatives as possible, including siblings, half-siblings, parents, aunts, uncles, cousins, grandparents, children and grandchildren.
- As part of recording your family genetic history, the counselors will ensure that it includes a list of each health condition diagnosed in a blood relative, the age at which they were first diagnosed, any genetic tests or specialized treatments that relatives received, and the ethnicity of each person with a health condition on both sides of your family.
- Your recorded genetic history also should list all deaths of blood relatives, including the causes and age at which they died.
- Remember that it’s fine if your family genetic history is not complete. Consider using upcoming family gatherings and celebrations to add to the information.
- When you are done recording your family history, keep the information in a safe place and be sure to share it with relatives and doctors.
- If you have used over-the-counter genetic testing kits, genetic counselors can help you understand the results.
Want to learn more about genetic counseling? Our genetic counselors will answer your questions during a live Twitter chat on Nov. 12, 2020, from 2 p.m.to 4 p.m. Eastern Standard Time on @HopkinsMedNews. Tweet your questions using the hashtag #GCADatHopkins or send a direct message to @HopkinsMedNews.