Research News Tip Sheet: Story Ideas From Johns Hopkins Medicine

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.

KETO DIET THERAPY RECOMMENDATIONS SET FOR ADULTS WITH EPILEPSY, OTHER NEUROLOGIC DISEASES

Within the past two decades, Johns Hopkins Medicine researchers and others have shown that ketogenic diet therapies — high-fat, low-carbohydrate and adequate protein diets that metabolize fat into chemicals called ketones that protect the brain and foster healthy neuron growth — are safe and effective in treating both children and adults with drug-resistant forms of epilepsy. However, while established guidelines are available for using ketogenic diet therapy to reduce seizures in children, there aren’t formal recommendations for adults.

Now, Mackenzie Cervenka, M.D., director of the Adult Epilepsy Diet Center and associate professor of neurology at the Johns Hopkins University School of Medicine, and her international collaborators have published the first set of recommendations based on current clinical practices and scientific evidence for managing ketogenic diet therapies in adult patients.

The new guidelines appear in the Oct. 30, 2020, issue of the journal Neurology: Clinical Practice.

“We wanted to guide medical professionals on how to manage adults who are using a ketogenic diet therapy,” says Cervenka. “We focused on epilepsy, but we also touch on the diet’s use in patients with other neurological disorders.”

Emerging evidence supports using ketogenic diet therapies in other adult neurologic disorders and medical conditions, such as migraines, Parkinson’s disease, dementia, brain tumors and multiple sclerosis.

“Ketogenic diets are called therapies for a reason,” Cervenka says. “They should only be employed with the support of medical professionals who are familiar with them as a clinical tool. The concern is when people follow them unsupervised. Our new recommendations are designed to make it easier for health care providers to give proper guidance.”

Ketogenic diets have been found effective in children with specific seizure types and epilepsy syndromes, which are often life-long conditions and require transition to adult providers for ongoing care.

“This goes back to Hippocrates, who wrote about fasting to suppress seizures,” Cervenka says. “There are many studies and articles about the benefits of fasting; however, it’s not a sustainable treatment. Ketogenic diet therapies create a metabolic state where you’re breaking down fats like fasting, but with adequate nutrition.”

To develop their recommendations, the researchers surveyed medical professionals at 20 institutions around the world on their results in treating an estimated 2,189 adults with ketogenic diet therapies for epilepsy and other neurologic diseases. Cervenka and her colleagues found that the therapy should be tailored to fit the needs of the individual patient, taking into consideration his or her: (1) physical and mental characteristics, (2) underlying medical conditions, (3) food preferences, (4) type and amount of support from family and others, (5) level of self-sufficiency, (6) feeding habits and (7) ease of following the diet.

“Most of the differences between the child and adult recommendations have to do with compliance,” Cervenka says. “Often, it’s more of a challenge for adults than for children.”

The researchers advise medical professionals to provide their patients with recipe ideas, individualized training on the ketogenic diet lifestyle from a dietitian or nutritionist, and guidance for meal planning and preparation before initiating the therapy.

Proper preparation and training, says Cervenka, provide the greatest likelihood of success, as patients often report difficulties coping with carbohydrate restriction. She adds that patients on a ketogenic diet therapy should take multivitamin and mineral supplements, along with drinking plenty of fluids.

STUDY LOOKS AT BARRIERS KEEPING CHILDREN FROM ATTENDING  DIABETES CAMPS, SUGGESTS REMEDIES

According to the Diabetes Education and Camping Association, over 20,000 North American children with type 1 diabetes attend diabetes camps and related programs each year. These activities, says the organization, enable children to improve their management of the disease, provide motivation and support by being with others who share the condition, and foster acceptance and understanding while having fun.

Although the benefits of diabetes camp programs are well established, minority youth are underrepresented in camp attendance. In a recent study — believed to be the first of its kind — Johns Hopkins Medicine researchers tried to define why this occurs, identify barriers to making it happen and find potential disparities in those barriers.

The findings were reported online Oct. 8, 2020, in the Journal of Pediatric Endocrinology and Metabolism.

In the study, 39 children, ages 5 to 15 with type 1 diabetes, and their primary caregiver were surveyed. The majority of the children were between ages 10 and 15 (59%), male (54%) and had an average time with diabetes of 2.9 years. Ethnically and racially, the participants were 67% white, 28% Black, 2.5% Hispanic or Latino, and 2.5% other groups. Only 18% of the children had previously attended a diabetes camp, although most (79%) had heard about them from their diabetes medical team. Less than half (46%) of the children and their caregivers were aware that financial assistance was available to help pay for attendance.

The most frequently reported barriers to attending diabetes camp — for all racial/ethnic groups, socioeconomic levels, and for children who had or had not previously attended camp —  were “There are no camps close to me” (59%), “Camp is too much money” (46%) and “I don’t want my child to attend sleep-away camp” (44%). Families of youths ages 10 to 15 were more likely to report “My child doesn’t want to attend sleep-away camp” (40%) than “I don’t want my child to attend sleep-away camp” (33%).

The average number of barriers reported per family was 2.3, with no significant difference in majority compared to minority children.

Most families were able to identify benefits of diabetes camps, including meeting other friends with diabetes (100%), improved independence in diabetes control (97%), improved diabetes control (94%) and learning about diabetes (94%).

Participants stated that diabetes clinics, online and social media groups, and the Juvenile Diabetes Research Foundation were the sources they most often sought for support and information about diabetes. However, minority families reported engaging with fewer sources and networks compared with white families.

“Our findings indicate that if barriers are mitigated, parents and caregivers would be more likely to send their children to diabetes camps,” says Risa Wolf, M.D., assistant professor of pediatrics at the Johns Hopkins University School of Medicine and senior author of the study.

The researchers suggest a number of strategies to improve access to diabetes camps, especially for minority and underserved populations. These include:

• Operating more day camps in urban settings to provide easier access for young children — and perhaps, serve as a springboard to overnight camps.
• Increasing diversity of camp staff to appeal to more minority youth.
• Inclusion of developmentally appropriate programs — such as counselor-in-training opportunities — to engage more adolescents.
• Increasing awareness of financial assistance and scholarships for camps, thereby encouraging families to seek more support.
• Increasing availability of camp information on social support networks and in diabetes clinics since most study participants cited them as primary knowledge resources.

“Although the sample size was small, our study findings clearly suggest that further research is needed — with more Black and Hispanic/Latino families participating — to gain greater insight into the barriers to attending diabetes camps, and then develop ways to overcome them,” says study lead author Gina Ferrari, M.S.N., M.P.H., F.N.P.-C, a recent graduate of the nurse practitioner program at the Johns Hopkins University School of Nursing.

POOR ENERGY METABOLISM MAY DRIVE HEART FAILURE AFTER ATTACK

After a heart attack, a patient can go on to develop cardiac failure, but not always. Previous research looking at the molecular mechanism behind this process in heart muscle cells showed that the heart enzyme calmodulin kinase II (CaMKII) relocates to the power factories of the cell — the mitochondria — shortly after a heart attack to drive the organ’s shutdown.

Now, Johns Hopkins Medicine researchers have shown in mice that CaMKII drains energy molecules from the mitochondria of heart muscle cells, causing the heart to work harder because it doesn’t pump as efficiently. They also revealed that it was possible to direct an enzyme to move energy out of the mitochondria, enabling it to fuel the heart muscle cells. In turn, they say, this prevents the physical signs of failure in mouse hearts.

The findings, published on Sept. 4, 2020, in Nature Communications, suggest that by targeting energy transfer in the heart’s muscle cells, it may be possible to prevent the progression to cardiac failure following a heart attack.

“It's really not clear clinically why certain people who have heart disease will progress to heart failure while others won't,” says Elizabeth “Betsy” Luczak, Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine, and lead author of the study. “Our findings suggest this could be a clue as to the ways to develop a therapy for people with dilated heart failure or even arrhythmias [irregular heartbeats] by enhancing transfer of ATP, the energy molecules in the cell.”

Following a heart attack, one of the classic signs of heart failure is when the left ventricle — the chamber of the heart responsible for pumping oxygenated blood throughout the body — increases in size from working too hard. This is because the tissue of the ventricle thins and doesn’t pump as well. In their study using a mouse model of a heart attack, Luczak and her colleagues turned on the enzyme creatine kinase to high levels in the heart muscle, which prevented CaMKII from draining ATP and resulted in the left ventricle no longer dilating and thinning.

According to the U.S. Centers for Disease Control and Prevention, heart failure eventually leads to death, with more than half of patients dying within five years of developing the condition.

GLOBAL STUDY SHOWS FOUR-MONTH TREATMENT FOR TUBERCULOSIS AS EFFECTIVE AS SIX-MONTH REGIMEN

With everyone focused on the ongoing COVID-19 pandemic, it’s easy to overlook the fact that there are other health threats still plaguing the world. Number one on the list is tuberculosis (TB), the disease that the World Health Organization calls the leading cause of death worldwide — some 1.5 million fatalities annually — from a single infectious agent (the microbe Mycobacterium tuberculosis). Now, the recently released results of an international clinical trial have shown that a four-month daily treatment plan using a high-dose, or “optimized,” course of the drugs rifapentine and moxifloxacin is as safe and effective as the existing standard six-month daily therapy.

The new regimen is the first successful short-course treatment option for drug-susceptible TB disease in 40 years. The findings from the clinical trial that led to its development — with significant involvement from Johns Hopkins Medicine researchers — were announced Oct. 21, 2020, by the research team funded by the U.S. Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH).

In the past 40 years, physicians have put their patients with TB on a six-month treatment regimen, which includes daily doses of the drugs rifampin, isoniazid, pyrazinamide and ethambutol for eight weeks, followed by 18 weeks of daily therapy with just rifampin and isoniazid. Looking for a way to shorten the regimen without sacrificing safety or efficacy, the CDC’s Tuberculosis Trials Consortium and the AIDS Clinical Trial Group (funded by the NIH’s National Institute of Allergy and Infectious Diseases) conducted one of the largest TB clinical trials in history. It involved more than 2,500 participants, ages 12 and older with newly diagnosed TB, who were enrolled at 34 clinical sites in 13 countries. The trial included 214 people with HIV infection.

Participants in the trial, known as Study 31/A5349, were given standard treatment or one of two four-month drug regimens for their TB — the first featuring high-dose rifapentine, instead of rifampin, and the second using high-dose rifapentine and moxifloxacin.

“We found that four months of treatment — with rifapentine and moxifloxacin — cured TB as well as the six-month standard treatment, had a comparable level of safety, and was well tolerated by patients,” says Richard Chaisson, M.D., director of the Johns Hopkins Center for Tuberculosis Research, professor of medicine at the Johns Hopkins University School of Medicine and one of four co-chairs of Study 31/A5349.

However, the regimen of high-dose rifapentine without moxifloxacin was found to be inadequate.

Along with their leadership role in the trial, the Johns Hopkins Medicine researchers followed 100 participants at a Johns Hopkins Medicine-funded center in South Africa and previously had conducted a number of animal studies that helped lay the groundwork for the latest investigation.

“This will certainly change how TB is treated in the United States [which still documents just under 10,000 cases annually] and likely, the world,” Chaisson says.

MOLECULAR ‘SWITCH’ CONTROLS ABILITY TO REPAIR HEARING LOSS IN MICE

In a study in mice, Johns Hopkins Medicine researchers have found a molecular ”switch” that turns off the animal’s ability to repair damaged cells in the inner ear. The findings shed light on regenerative abilities that are present in many species of birds and fish, but get turned off in mammals, including humans.

The study was published Sept. 8, 2020, in The Proceedings of the National Academy of Sciences.

“We might have for the first time identified something that explains why humans lost the ability to repair cells related to hearing loss,” says Angelika Doetzlhofer, Ph.D., associate professor of neuroscience at the Johns Hopkins University School of Medicine, and co-author of the study.

More than 37 million adults in the United States report hearing loss. In the majority of cases, it results from damage to sound receptor cells deep within the human ear known as hair cells. These cells line the spiral-shaped walls of the cochlea, a bony structure in the inner ear, and capture sound waves reverberating in the area. Then, they convert the vibrations into electrical impulses that are carried to the brain by nerves.

Hair cells are kept healthy by a layer of cells called supporting cells. In birds and fish, supporting cells can function as progenitors to replace lost hair cells. Recent studies of mammals have shown that supporting cells have some regenerative potential early in life, before the animals start hearing. For example, supporting cells in mouse pups are able to create new hair cells at birth. However, the ability to repair or replace them stops within a week. At that point, any damage done to the hair cells is irreversible.

Based on these data from previous mouse studies, Doetzlhofer and study co-author Xiaojun Li, Ph.D., a postdoctoral fellow in her laboratory, looked to the rodents as a way to better understand what controls the decline in regenerative ability in mammals.

The researchers achieved this by following the levels of a protein and micro RNA in mice, called LIN28B and let-7, respectively. LIN28B and let-7 are what scientists call ”mutual agonists,”’ meaning they control each other’s function within the cell.

They found that when let-7 levels ramp up, LIN28B levels drop at the same time, turning off the mouse’s regenerative ability.

The two researchers found that without LIN28B, hair cell regeneration does not occur. They tested this by using cochlear tissue and cells from genetically engineered mice that enabled the protein and its agonistic RNA to be turned on and off as needed.

The researchers say that their findings suggest LIN28B is the deciding factor as to whether or not the hair cells retain their regenerative abilities. LIN28B, they believe, promotes the regenerative process by turning on progenitor-specific genes in supporting cells, which then reprograms supporting cells into hair cell progenitor-like bodies.

“The most exciting part was seeing the dramatic effects of manipulating these factors. We began the experiment hoping to get any type of response, and to see a restoration regeneration capability was really thrilling,” says Doetzlhofer.

The researchers say that a better understanding of the biology behind hair cell regeneration may lead to the development of future treatments for hearing loss.

This research was supported by the National Institute on Deafness and Other Communication Disorders and the David M. Rubenstein Fund for Hearing Research.

LIFE WITH DIABETES: TEENAGE JOHNS HOPKINS PATIENT THRIVES A YEAR AFTER HER DIAGNOSIS

When, in late 2019, 12-year-old Izabelle Macht of Walkersville, Maryland, started drinking excessive amounts of water, taking frequent bathroom breaks, losing weight and having sweet-smelling breath, her mom, Danielle Macht, did what any other parent would do — she started to worry. So, Danielle did an online search to try to identify the cause behind her daughter’s new symptoms. “The first thing that showed up was type 1 diabetes,” she recalls. After a trip to the pediatrician and a local emergency room, doctors confirmed Danielle’s fear: Izabelle indeed had type 1 diabetes.

November is American Diabetes Month. According to the U.S. Centers for Disease Control and Prevention, diabetes is the most common chronic illness in children and teenagers, with more than 200,000 people under the age of 20 currently diagnosed.  And the number of cases continues to rise each year.

Diabetes is a disease in which a person’s body does not make or efficiently use the hormone insulin, causing the blood level of the sugar glucose to rise. If untreated, diabetes can lead to other health concerns, such as vision problems and nerve or kidney damage. There are two main kinds of diabetes found in children and teens — type 1 and type 2 — with most kids being diagnosed with type 1.

For Izabelle and her family, life changed drastically after they found out she had diabetes. Izabelle and her parents learned how to check her blood glucose levels frequently, give insulin injections, count carbohydrates and properly respond if her blood glucose level got too low.

To help manage her diabetes, Izabelle has routine visits with her pediatric endocrinologist, Sandra Salsberg, M.D., at the Johns Hopkins Health Care and Surgery Center in Bethesda, Maryland. Izabelle now has a continuous glucose monitoring device that automatically checks her blood sugar every five minutes without having to prick her finger. The monitor enables Izabelle’s parents to follow her blood sugar levels remotely as well. Izabelle also has started on an insulin pump that provides her with the needed hormone more frequently throughout the day without needing injections.

Nearly a year later, the now-13-year-old Izabelle has become accustomed to the changes brought by her diabetes. Danielle says Izabelle is “doing wonderfully” and continues to live her life as she was before her diagnosis: playing softball, swimming and having sleepovers with friends. “She handled it so much better than I did,” Danielle says. 

“Izzy is a healthy girl who has type 1 diabetes,” Salsberg says. “She and her parents are doing all of the hard work to control her diabetes. My job is to give them the tools to make diabetes fit into her life. Right now, those tools involve an insulin pump and continuous glucose monitor, but that may change over the next few years. As she evolves as a person, the management of her diabetes will continue to evolve as well, and I will continue to find the regimen that works best for her and her family.”

For parents who notice a change in their child as Danielle Macht did, she offers sound advice. “Don’t doubt yourself,” Danielle  says. “If you think your child is exhibiting any of the symptoms of type 1 diabetes, don't hesitate to take him or her to the pediatrician.”

Izabelle, her parents and Salsberg are available for media interviews.