Mothers and babies: Moms recovering from substance use disorder
They may sleep in drainage ditches, alleys or motel rooms. The cold of winter, blistering Texas heat and even hunger don’t matter.
“All I cared about was getting my next fix,” said Diana Garcia, one mother who has recovered from opioid use disorder at Casa Mia with her now 3-year-old daughter, Eliana.
The recovery home is one of only a few in Texas that gives mothers with substance use disorder the opportunity to recover with their children.
Casa Mia, which opened in November 2018, provides the supervision, structure, support and hope mothers with substance use disorder need to turn their lives around.
Ordinarily, when pregnant women or mothers with children are using substances, Child Protective Services will seek safe living arrangements for children. If arrangements can’t be found with family or friends, they likely will enter the foster care system.
“Many of these mothers have experienced significant personal trauma. While placing their children in foster care may initially provide safety, it prevents mothers and babies from bonding and adds to a continuing cycle of trauma that can impact future generations,” said Lisa Cleveland, PhD, APRN, FAAN, professor of nursing.
How Casa Mia works
Cleveland founded Casa Mia with Kevin Downey, PhD, who serves as CEO of Crosspoint Inc. It has offered behavioral health care, recovery support and transitional residential services for more than 50 years.
The School of Nursing and Crosspoint provide safe, supervised group living arrangements for pregnant and parenting mothers and their children at Casa Mia, located in a comfortable, two-story, brick home in San Antonio’s Monte Vista neighborhood. The home’s capacity is 20 women and children. Crosspoint’s staff supervises life at the house and provides recovery-focused case management while the women attend treatment programs offered by community partners and work toward sustained recovery.
The mothers are encouraged to visit their babies in the hospital, where the newborns may stay for weeks if they experience neonatal abstinence syndrome or withdrawal symptoms. The symptoms may include inconsolable crying, seizures, weight loss, difficulty eating, vomiting and diarrhea.
The mothers learn to practice kangaroo care, a comforting technique in which they hold their babies against their bare chest. In earlier research, Cleveland found that this practice can reduce neonatal abstinence syndrome symptoms, support on-demand breastfeeding and promote mother-baby bonding.
Mothers also can reunite with older children through increased visitations, leading to overnight stays at Casa Mia. Some preschool children eventually move in full time.
Casa Mia partners closely with local programs that offer a community approach to helping mothers recover from substance use disorder by attending a 13-week series of parenting and life skills classes. One of those programs, which Cleveland helped disseminate statewide, is the Mommies Program that promotes the use of successful medication-assisted treatments, such as buprenorphine and methadone.
A mother’s progress is defined individually but is typically focused on establishing and maintaining recovery, securing a continuing source of income, obtaining stable housing, and regaining or maintaining custody of her children, Cleveland explained.
“One of our most successful mothers moved into Casa Mia in November 2018 and progressed so quickly that she was reunited with her 7-month-old son that Christmas,” Cleveland said.
That mother has thrived in her recovery, now living independently with her son, Cleveland added. She moved into her own apartment with her son and has completed the education needed to become a peer counselor in one of Crosspoint’s women’s recovery programs.
“Since it opened in 2018, Casa Mia has provided housing for 80 adult women and 51 children,” Cleveland said. “Ten of our residents have given birth while living at Casa Mia and at least 34 moms have regained custody of their children. Residents who graduate from Casa Mia are eligible to return if they encounter challenges in their recovery or housing status, and five women have done this so far.”
‘It’s like a family’
Garcia, who lived at Casa Mia with her newborn daughter for seven months, said that while she was pregnant, she worried she would lose custody of her child. When a caseworker with Child Protective Services told her about Casa Mia, she saw it as a chance to change. Keeping her baby became her goal, and Casa Mia played a big part in stabilizing the young family.
“Living here is not easy,” Garcia said at the time. “There are a lot of restrictions. A lot of times I didn’t want to do this anymore. But since being here I haven’t had cravings [for drugs]. I have Eliana. I cannot imagine a day without her. We all have chores, and we all help each other with advice and child care. It’s like a family.”
When Garcia began working, Eliana went to the child development center at the Healy-Murphy Center. Working in partnership, the center and the School of Nursing provide a variety of services for their clients. While the center provides child care for Casa Mia residents, the School of Nursing provides nutrition and health education for pregnant and parenting teens who attend high school or take GED classes at Healy-Murphy. The School of Nursing also runs a pediatric clinic for teen parents and their children.
With Casa Mia’s capacity holding at more than 80%, Cleveland knew she needed a bigger place. She received $3.8 million in fall 2020 from Texas Health and Human Services to move Casa Mia to a new women’s wellness campus being built by Crosspoint on the city’s East Side at 1500 Semlinger Road. The new facility, expected to open in 2024, will double Casa Mia’s capacity.
“There is a similar women’s campus in Houston for mothers and babies to recover together, but ours will be the first in the state to offer an on-site [neonatal abstinence syndrome] nursery and primary care clinic designed and operated by our School of Nursing,” Cleveland said.
Educating nursing students
Casa Mia has positively impacted nursing students such as Neal Hungerford, who has since graduated. His work-study assignment was to support the School of Nursing programs at Casa Mia.
“I wish that more nursing students could come here. This is a real eye-opening experience,” he said. “It makes you a better nurse. You’re definitely more compassionate.”
There also is a clinical rotation for nursing students led by Martha Martinez, MSN, RN. Nursing students, for example, have taught the mothers how to make sensory toys for their babies. Through the activity, the mothers learn what to expect regarding developmental milestones. In an effort to continually improve the program, the School of Nursing keeps statistics on the success of the program and conducts exit interviews with the moms as they move on to their new lives.
Expanding the model
In September, the School of Nursing received its Texas Department of State Health Services funding to work with national nonprofit partners to start similar programs in two other Texas cities.
“In Fort Worth, we are partnering with the WestCare Foundation and in Corpus Christi with Dimas Charities. Initially, the School of Nursing will be involved in helping them start their programs to ensure fidelity to the Casa Mia program model. Going forward, there may be potential for expansion of our role similar to the campus model here in San Antonio,” Cleveland said.
Guided by the voices of mothers
The inspiration for Casa Mia came from mothers who are involved with the Bexar County Neonatal Abstinence Syndrome Collective, a collaborative that Cleveland founded and chairs.
“It’s great to see their ideas become a reality and for this program to be so successful,” Cleveland said.
To learn more about Casa Mia, visit CasaMiaSanAntonio.com.
Trauma game changer
Theresa Hernandez was three weeks away from giving birth to her third child. As she got ready for bed, the last stop was the bathroom. She noticed that she was bleeding.
“When I stood up, I felt pain. It felt like the baby was coming out,” she said.
Her placenta had ruptured.
“I lost a lot of blood, so I told my boyfriend to call an ambulance,” Hernandez said.
After receiving whole blood in the ambulance and being transported to the hospital, doctors delivered her son by emergency C-section. The quick transfusion of whole blood to Hernandez—before ever entering the hospital—is what initially saved her life and that of her son, said C.J. Winckler, M.D., assistant professor of emergency health sciences in the School of Health Professions and deputy medical director of the San Antonio Fire Department Emergency Medical Service.
Because of lessons learned on the battlefields of Iraq and Afghanistan, South Texas patients are among the first in the nation to receive lifesaving whole blood transfusions before they reach the hospital. The effort, initiated by UT Health San Antonio faculty with military trauma experience, is part of a partnership under the Southwest Texas Regional Advisory Council, which oversees trauma and emergency health care projects and programs in 22 counties in South Texas, including the San Antonio area.
“There is no place in the U.S. where an entire region of 22 counties, across 26,000 square miles, with more than 50 hospitals and 70 EMS and helicopter EMS agencies, has access to whole blood for injured and bleeding patients, except for South Texas,” said Donald Jenkins, M.D., professor of trauma and emergency surgery. He serves as vice chair for quality in the Department of Surgery at University Hospital and associate deputy director of UT Health San Antonio’s Military Health Institute.
San Antonio is the only city in the nation with a broad network to transport whole blood to trauma sites. The move to whole blood transfusions has transformed emergency response, with a 25 percent reduction in deaths due to hemorrhage in the region between January 2018 and January 2019, Dr. Jenkins said. But whole blood transfusion is not new.
Whole blood—blood that has not been separated into components—is the original transfusion fluid. It’s what’s running through our veins. From the early 1900s through World War II, if a soldier needed blood, it was transfused from another soldier. During the Vietnam War, whole blood was donated in the U.S., refrigerated and sent to Vietnam, where 10 million units were used. The practice was discontinued after Vietnam because of increased HIV and hepatitis C viruses in donors. “That was before we had testing for viruses in the blood,” Dr. Jenkins said.
With a dwindling blood supply because of the viruses, and a shift toward specialized blood products for transfusions, it became standard practice to use blood components—red blood cells, platelets and plasma—instead of whole blood for transfusions at hospitals throughout the U.S. Generations of doctors were taught that using blood components was the best and most efficient way to transfuse blood.
That changed as the U.S. became embroiled in the wars in Iraq and Afghanistan. There was a new type of warfare: improvised explosive devices. IEDs cause significant blast injuries that result in hemorrhage. Many blast victims bled to death before they reached a field hospital. To save lives, military physicians began researching factors that could lead to better survival.
It takes 20 to 25 minutes to bleed to death, so time was identified as the most important factor for survival. If blast victims received a blood transfusion before ever reaching the field hospital, 10 percent of the victims could be saved, research concluded. But what would be the best products to use?
“When you take a pint of blood and separate it into parts, you have a much more diluted product than if they just drew blood, sealed the bag and put it in the fridge,” Dr. Jenkins said. Reconstituting the blood products also is challenging because of their different storage, testing and temperature requirements. On the battlefield, it was impossible.
“Whole blood is what these patients need. They need oxygen from the red blood cells, clotting from the platelets and plasma to carry it through the body. These factors are all in whole blood, and refrigerated whole blood can be safely stored for 35 days,” he said.
After retiring from the military in 2008, Dr. Jenkins and colleagues in Pennsylvania and Norway continued whole blood research in the civilian health care system. While at the Mayo Clinic in Rochester, Minnesota, he initiated a whole blood transfusion program for trauma patients in the hospital.
When he arrived in San Antonio in 2016, he studied three years of data from University Hospital—one of two Level 1 trauma centers in South Texas. Patients arriving at the trauma center in need of an emergency transfusion had a 40 percent death rate. For those with ongoing bleeding requiring a replacement of their entire volume of blood, the death rate rose to 76 percent.
“It didn’t take too much convincing [to switch to whole blood],” he said. “All you had to do was show the numbers. After beginning a whole blood protocol at University Hospital, the death rate dropped to 13.8 percent.”
He then worked to provide transfusions to patients before they reached the hospital. Whole blood transfusions are now possible on helicopters and in San Antonio Fire Department ambulances, and the program is spreading to other hospitals and ambulance companies in the region. Dr. Jenkins and others are now consulting nationally on the use of whole blood.
Tiffany Kieschnick-Rivas knows the advantages of whole blood transfusions firsthand. She wouldn’t be alive without one. While driving home in January, she had a stroke. Her car swerved off the road, flipping down an embankment into a ravine with standing water.
By the time she was rescued, she had no pulse and was not breathing.
“Our paramedics gave her a unit of whole blood and she began to blink and move her arms and legs,” Dr. Winckler said. Two more units were transfused on the helicopter that brought her to University Hospital. “For just under four minutes, she was dead. But now she will live another 40, 50 or 60 years.”
The mother of two sons said she’s grateful she received whole blood at the scene of her accident.
“I would not be here without it,” she said.
A golden celebration
Annual gala establishes patient care endowment
A record attendance of nearly 1,800 guests helped raise more than $500,000 at the annual President’s Gala to establish the Peggy and Lowry Mays Patient Care Endowment.
The endowment supports the Patient Supportive Care Program at the Mays Cancer Center, home to UT Health San Antonio MD Anderson Cancer Center.
The gala honored philanthropists Peggy and Lowry Mays and also marked the 50th anniversary of the Joe R. and Teresa Lozano Long School of Medicine and its continued service to South Texas.
“We are so grateful to Peggy and Lowry and all they have done for our cancer center through the years,” said UT Health San Antonio President William L. Henrich, M.D., MACP.
The Patient Supportive Care Program provides critical services for cancer patients with the greatest financial needs. The endowment also will fund wellness and survivorship programs that help patients lead healthier lives after they complete treatment, Dr. Henrich said.
“This program is vital to caring for our patients in the compassionate way we would want to be treated ourselves,” he said. “They embody our mission to provide the very best in care to patients close to home.”
Peggy and Lowry Mays and their family have been key supporters of the cancer center since its early years. Peggy Mays, a former member of the Board of Governors of the cancer center, founded its annual fund program called the Cabinet in 1996. The Cabinet has raised nearly $8 million over the program’s 23-year history. Cabinet gifts provide essential support for innovative cancer research, state-of-the-art equipment, and critical cancer education and patient care programs.
Kathryn Mays Johnson, daughter of Peggy and Lowry Mays, is president of the Mays Family Foundation. She is a member of the Mays Cancer Center’s Board of Governors and is a past president of the SA Cancer Council. Over the past 35 years, the council has supported the cancer center through fundraising, volunteer services, community outreach and education, and patient assistance. The SA Cancer Council has raised more than $5 million.
In February 2018, the Mays Family Foundation increased its legacy gift to the cancer center to $30 million. The contribution provided a substantial endowment to perpetually support the director of the Mays Cancer Center and establish up to 10 new permanent distinguished endowed chairs for the recruitment and retention of key faculty members. The gift also established the Mays Cancer Center Excellence Endowment to support top priorities for future success and long-term sustainability.
“My parents, brother and I have all been touched by cancer,” said Johnson. “Because we know what it’s like to hear the difficult words, ‘You have cancer,’ and have appreciated the excellent care we have received here at the Mays Cancer Center and at MD Anderson, we feel compelled to give back.
“We are pleased that our investments are developing our cancer center’s affiliation with MD Anderson and have been impressed with the rapid progress of this relationship that will benefit cancer patients in our region.”
Cured
[Click here for a timeline of discovery milestones]
By Rosanne Fohn
Joey Libby, 26, holds a job at a call center and does odd jobs for extra cash. While the outside work he does on weekends is demanding, especially as the temperatures rise, he does it willingly because for eight years—most of his teens and early 20s—his life was limited by a disease that few survived at that time.
Joey was just 15 when he was diagnosed with hepatitis C. The symptoms came quickly and were punishing.
“I wasn’t keeping any food down, not even water. It seemed to me that I had a stomach bug,” he said. “I tried medicine and I rested, but my mom had an instinct that she needed to take me to the hospital. She said, ‘Something’s just not right.’”
Joey went through a series of tests. Then the diagnosis was delivered—and the news that he was in liver failure.
“They told me that if I had not come to the hospital that day, I might have died,” Joey said.
Hepatitis C is a blood-borne virus that slowly destroys liver function. About 3.5 million people in the U.S. have chronic hepatitis C and 70 to 80 percent of them do not have symptoms until the disease has significantly progressed. According to the Centers for Disease Control and Prevention, more Americans die from hepatitis C than any other infectious disease. Hepatitis C also is a major cause of liver cancer.
Yet finding a cure for the disease that wasn’t even known or named until 1989 has been hailed as one of the biggest modern success stories in scientific research. In record time, scientists say, the virus has gone from unknown to almost 100 percent curable. It has claimed many lives in the process: In 2014, deaths associated with hepatitis C reached an all-time high of 19,659, surpassing the combined number of deaths from 60 other infectious diseases, including HIV, pneumococcal disease and tuberculosis.
But Joey wasn’t one of them. Instead, his path to recovery helped lead the way for researchers to find a cure.
It wasn’t an easy road.
It was 2007 when Joey was diagnosed with the disease. He was placed on the liver transplant list and started the standard hepatitis C treatment for that time—daily shots of an antiviral drug called interferon. The drug had severe side effects, with only 10 to 20 percent of patients being cured.
“When I was sick I couldn’t play sports, I couldn’t work out, I was depressed. For a while I even considered suicide. It was just too much,” he said.
Joey returned to school, but his eyes and skin turned yellow because of low liver function, and he was retaining fluid in his abdomen. As his condition worsened, he was homeschooled. He got a reprieve with a liver transplant on June 19, 2008; however, the good news was tempered.
“Unless the hepatitis C is cured, the virus continues circulating in their blood and infects the new liver, usually within a few months of transplant. One-third of them get cirrhosis again within five years,” said Fred Poordad, M.D., professor of medicine at UT Health San Antonio and chief of hepatology in the Liver Transplant Program at University Transplant Center, a partnership between UT Health San Antonio and University Health System.
It is unclear exactly how Joey contracted hepatitis C. Most people are diagnosed when they are age 50 or older, but both of his parents had the virus. Hepatitis C is found worldwide and is spread through contact with blood or semen, including using shared drug injection needles, inadequate sterilization of medical equipment, unscreened blood or blood products, accidental needle sticks and sexual intercourse with a person who has hepatitis C. The disease can also be spread from mothers to children during birth.
Baby boomers, those born between 1945 and 1965, are the most affected because of exposure during medical procedures after World War II, when injection and blood transfusion technology was not as safe. Many of these baby boomers unknowingly transmitted it to others.
A few years after Joey was diagnosed, his father died. His mother, Doris Libby, had learned she had the disease a few years before, but had refused treatment because fatigue was her only symptom.
Then she met liver specialist Eric Lawitz, M.D., a professor of medicine at UT Health San Antonio. Dr. Lawitz was conducting clinical trials through his medical practice, the Texas Liver Institute.
“I was in Dr. Lawitz’s office and I told him about Joey,” she said. “He told me about one of the trials, and the way he expressed it, he was bursting with enthusiasm and excitement. He wanted both of us to go on the study.”
The trial was for patients in two groups who had not benefitted from previous treatments—those, like Doris, with hepatitis C who had advanced liver disease, and patients like her son, who had received a liver transplant but whose liver disease had returned because of hepatitis C.
The year was 2014. By then, Dr. Lawitz had seen many treatments for hepatitis C come and go, with limited success.
But this one seemed different.
A long road
Dr. Lawitz was in medical school when hepatitis C was first discovered. The first standardized treatment—interferon—was approved by the Food and Drug Administration in 1991. As his medical training progressed, first in internal medicine and then with fellowships in gastroenterology and hepatology at Brooke Army Medical Center in San Antonio, he became involved in some of the early research to improve treatments.
One of the challenges of finding a cure for hepatitis C is that there are six strains of the disease, based on the geographic location where the strain developed. In the U.S., genotype 1 is the most common type. Another variable is the extent of liver scarring called fibrosis, which when severe is called cirrhosis.
When Dr. Lawitz opened his private practice in 2004, it included cutting-edge liver disease research. Interferon, given to boost the body’s immune system and reduce the growth of cancer and viral cells, was the standard treatment for hepatitis B. But to treat the chronic and deadly hepatitis C, he knew it wasn’t enough.
Interferon has terrible side effects, including flu-like symptoms, fatigue and depression. While it helped the body recognize viruses and eliminate them, as soon as patients stopped taking it, the virus would come back.
“Back then with our research, we were just inching along, trying to squeeze another 5 percent cure rate out of interferon by changing the dose or duration of therapy,” Dr. Lawitz said.
Then doctors began adding an antiviral drug, ribavirin, to their treatment regimen. The pills seemed to work at preventing relapse and more than doubled cure rates from 10 or 20 percent to about 40 percent. But it also had adverse effects such as anemia, gastrointestinal issues and rash. Attempts to keep interferon in the bloodstream longer meant patients were given weekly long-acting injections of interferon and up to six pills daily for months.
While Joey endured these difficult regimens with limited success, the field of medicinal chemistry was beginning to blossom with a new approach. Instead of focusing on strengthening the body’s immune system to fight the virus using existing treatments, scientists began studying the use of direct-acting antivirals to target specific parts of the virus and prevent it from reproducing. These new drugs held the promise of a shortened treatment length, minimal side effects and, because they targeted the virus itself, improved response.
Several physician-researchers around the country were invited to evaluate the new drugs in clinical trials. Among them were Dr. Lawitz and Dr. Poordad, who at that time was chief of hepatology and liver transplantation at Cedars-Sinai Medical Center in Los Angeles.
“If they worked, we knew direct-acting antivirals would change the field forever,” Dr. Poordad said.
They were on the cusp of finding a cure for the disease that seemed unconquerable.
The first clinical trials of direct-acting antivirals began in 2008 by adding them to standard immune-building treatments. Amazingly, three short years later, the FDA approved the first two direct-acting antiviral therapies for genotype 1.
Cure rates escalated to 79 percent with some treatments.
“With these two regimens, we got high cure rates, but we still had significant adverse events, so it helped in one way but it wasn’t patient-friendly in the other,” Dr. Lawitz said.
So, the physician-scientists teamed up, and the work went on.
Having met at various professional research meetings, Dr. Lawitz invited Dr. Poordad to join his practice in 2012, when both also became professors of medicine at UT Health San Antonio.
Their academic backgrounds and clinical success provided them with opportunities to assist and advise pharmaceutical companies in the design and conduct of some of the major hepatitis C clinical trials, including Harvoni, now a common drug used in the treatment of hepatitis C, Dr. Lawitz said.
Then came the study that changed the lives of Joey and his mother.
In this clinical trial, patients received a 12-week course of a direct-acting antiviral drug combined with an inhibitor of a key viral protein found in hepatitis C.
The trial showed an overall cure rate of 94 percent for patients with a liver transplant and returning hepatitis C, like Joey, and a cure rate of 83 percent for patients with advanced cirrhosis, like his mom.
“The medicine didn’t make me feel bad and it was all pills, which was cool because I didn’t have to take shots,” Joey said.
The trial was a highlight of Dr. Poordad’s career, and he presented the results at the International Liver Congress of the European Association for the Study of the Liver. The combination therapy received FDA approval in 2015. But the study had a much more profound effect on the Libbys.
Both Joey and his mother were cured.
A game changer
In June 2016, the first agent to treat all six forms of hepatitis C in adults, called Epclusa, was approved. Drs. Lawitz and Poordad have investigated myriad drugs now approved by the FDA. Their work has appeared in premier research journals and helped shape guidelines in the treatment of hepatitis C.
The most recent drug approved by the FDA was Mavyret in 2017; it treats all genotypes of hepatitis C. Some of the drugs have also been approved for use in pediatric patients.
“The bottom line is that in a little more than a decade, we have conquered hepatitis C,” Dr. Lawitz said. “We now have many direct-acting, all-oral medications that cure 95 to 100 percent of patients in eight to 12 weeks of therapy with very minor side effects. Additionally, we can successfully re-treat 96 percent of [previous direct-acting antiviral] failures.”
Only 1 in 1,000 patients in the hardest-to-treat categories cannot be cured.
“To me, the biggest surprise was how quickly the pace of development occurred,” Dr. Lawitz said. “The incremental steps from drug to drug and clinical trial to clinical trial were fairly big. To get from 40 percent to nearly 100 percent cure rate with only minor adverse effects in that short of a time is unheard of.”
However, it didn’t come without drawbacks.
“Liver disease has a high death rate. I’ve seen too many patients pass away. There is not one patient who stands out for me. I’d say that many stand out. They helped drive me and helped me remember why we do this work,” Dr. Poordad said. “We’re very thankful to the many patients along the way. Without them we wouldn’t have had these successes. They trusted us with their lives.”
While finding a cure happened in record time, the doctors know there is more work to be done. They want to see the fruits of their labor made available throughout the world to aid in total eradication of the disease. A vaccine could help achieve this goal.
For Joey, the journey to health was more than a decade-long process that unfortunately ended a year after his father died. Today, Joey is just glad to be able to lead a normal life, working two jobs and exercising regularly.
Doctors still routinely check his liver function “and I’m still doing well,” Joey said. “I’m just living my life.”
Discovery Timeline
1989: Hepatitis C is identified for the first time. It has six types, or genotypes, based on the geographic location where the strain developed. Genotype 1 is the most common in the U.S.1991: Interferon is approved by the FDA to treat hepatitis C. There are many classes of interferons, which are used to boost the immune system to fight viruses, not directly kill viral or cancerous cells. Cure rate: about 10-20 percent.1992: Blood tests are perfected to screen for the hepatitis C virus. These tests effectively eliminated the virus from the blood transfusion supply.1998: Ribavirin, an antiviral medication, is added to the standardized treatment of interferon. Cure rate: about 40 percent.2001: Pegylated interferon is introduced to help interferon stay active in the bloodstream longer. Treatment regimens include injections and up to six ribavirin pills daily for six months. Cure rate: about 41 percent.2003: A combination of interferon and ribavirin is approved for treating pediatric patients.2005: Hepatitis C cells are grown in a lab for the first time, leading to the first study of the virus' life cycle.2006: A new class of oral drugs, called direct-acting antivirals, is developed. The drugs are aimed at directly stopping the spread of hepatitis C in the body by targeting specific steps in the virus’ life cycle.2007: Sofosbuvir, an inhibitor of a key viral protein in hepatitis C, is designed to decrease the amount of hepatitis C virus in the body and shows promise when used with standardized treatment. A series of clinical trials showed a cure rate of more than 90 percent in 12 weeks for genotypes 1, 2 and 3. |
2008: The first clinical trials of direct-acting antivirals begin.2011: Direct-acting antivirals are approved by the FDA to treat hepatitis C. These include boceprevir, used in combination with pegylated interferon and ribavirin, for a cure rate of up to 66 percent in genotype 1 patients. Telaprevir also was approved in combination with pegylated interferon and ribavirin for a 79 percent cure rate of genotype 1.2014: Ledipasvir, another direct-acting antiviral, used in combination with sofosbuvir, is approved by the FDA for genotypes 1, 4, 5 and 6. Known by its brand name Harvoni, the drug was the first hepatitis C treatment contained in one pill. Cure rate: 95 percent within eight weeks.2015: The FDA approves a 12-week course of the direct-acting antiviral agent daclatasvir combined with sofosbuvir, with and without ribavirin, for genotypes 1 and 3. Overall cure rate: 94 percent for patients with a liver transplant and returning hepatitis C. Cure rate for patients with advanced cirrhosis: 83 percent.2016: Epclusa, a combination of sofosbuvir and velpatasvir antiviral medications, is approved by the FDA to treat all six forms of hepatitis C in adults. Cure rate: 95 percent in 12 weeks.2017: Mavyret, a combination of the viral inhibitor glecaprevir and the antiviral agent pibrentasvir, is approved by the FDA to treat all genotypes of hepatitis C. Cure rate: 92-100 percent in eight weeks.Sources: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, the Hepatitis C Support Project, Eric Lawitz, M.D., Fred Poordad, M.D. |
Herbal hope for oral cancer
Mother Nature has a way of hiding cures for diseases in plants and minerals, awaiting human discovery.
This may be the case with thymol, a compound found in several plants, including thyme, oregano, rosemary and bay leaves.
“Thymol is already known to have anti-microbial, anti-fungal, anti-inflammatory and anti-oxidant properties,” said Cara Gonzales, D.D.S., Ph.D., associate professor in the Department of Comprehensive Dentistry. Due to its medicinal properties, thymol is already an ingredient in a leading mouthwash, cosmetics and other products.
Dr. Gonzales and her team recently conducted laboratory and animal research that showed thymol may have merit as a preventive agent and treatment for oral cancer.
They found that thymol was effective in preventing the proliferation of oral cancer cells. In animal models of human oral cancer, the team showed thymol to be effective as an anti-tumor agent.
“Our findings provide the first evidence of thymol’s novel anti-tumor effects against oral cancer in animals,”
Dr. Gonzales said.
The team further discovered thymol selectively kills cancer cells by acting on their highly active mitochondria, which produce energy to allow cancer cells
to grow.
“We show that thymol induces mitochondrial dysfunction and cell death, and it may be effective against several types of cancer,” she said.
Dr. Gonzales’ research was published in the Journal of Oral Pathology & Medicine. UT Health San Antonio has a patent on a thymol mouth rinse to prevent oral cancer and on its mechanism of action to use as a treatment for oral cancer. She hopes to conduct human clinical trials in the future.
Attacking the opioid epidemic
Lisa Cleveland, Ph.D., RN, assistant professor of nursing, has been awarded two grants totaling more than $4 million to educate Bexar County first responders on how to identify and reverse opioid overdose. The grants were from the Texas Health and Human Services Commission.
The first was a four-year, $2.2 million contract to purchase naloxone to provide training to first responders—including friends and family of opioid users—to identify and reverse an overdose using the medicine, and teach them where to refer users for further treatment. The second grant was for $1.87 million for the first year of a two-year program to bridge the gap between EMS response and the referral of opioid users into recovery and substance use treatment services, and to purchase naloxone.
Double whammy
Daniel Edelen loved riding his bike, playing baseball and basketball, and being a Cub Scout in Indianapolis, Indiana, where the Edelen family had recently moved from San Antonio in 2003.
Photo: Jennifer Jennings Images, Inc.
One day in mid-May 2004, however, the family began a health journey that changed everything. Daniel, a first-grader, began having fever and stomach aches. They were so severe that Daniel’s mother, Joan Edelen, took him to the doctor three times that week.
“[The doctor] gave us some antibiotics to start right away and said he thought I would feel better soon,” explained Daniel, now 20.
That weekend, Daniel went for a bike ride and had trouble catching his breath. By Monday, he had bruises all over his body and a blood streak going through his left eye. They rushed to the pediatrician.
“At that point, I couldn’t sit up and was having a lot of trouble breathing,” Daniel recalled. “The pediatrician sent us to the children’s hospital emergency room.”
They immediately X-rayed his stomach and ordered blood tests. After 30 minutes, the family heard what no family wants to hear: Daniel had childhood leukemia.
“The doctors said I had to start chemo right away or I might not make it through the night. There was a tumor of white blood cells in my chest that had almost totally covered both of my lungs, which was causing me not to be able to breathe,” Daniel said. That day, May 17, he began what would become 3 1/2 years of treatment and continuing years of follow-up.
Instead of splashing in the pool and playing with friends that summer, Daniel fought a disease that, until the early 1960s, only 4 percent of children survived. By the 1980s, research discoveries had made it possible for approximately 80 percent of children to survive childhood leukemia. But that 20 percent mortality rate weighed heavily on the family.
Daniel’s treatment continued through the fall and into winter. And then came another test, this one from a little-known fungus: Aspergillus.
Aspergillus is a common mold found in soil, dust, decomposing plant matter and even in some foods and spices. Infections, called aspergillosis, are rare, affecting about 12,000 people each year in the U.S. The fungus focuses on individuals with compromised immunity due to childhood leukemia, lymphoma, AIDS, organ transplantation, severe burns, diabetes, poor nutrition or long-term steroid use.
It was early December when Daniel was diagnosed with aspergillosis. According to the Infectious Diseases Society of America, the mortality rate in immunocompromised patients is 40 percent or higher, especially in patients with widespread infection.
“We were very worried about him,” said his father, Chris Edelen. He remembered a former neighbor from San Antonio, Thomas Patterson, M.D., who also happened to be an infectious disease specialist at UT Health San Antonio. He quickly gave him a call. It was a fortuitous connection.
Dr. Patterson, professor and chief of the Long School of Medicine’s Division of Infectious Diseases, is an international expert in fungal diseases who had helped develop one of the leading drugs to fight aspergillosis at that time—voriconazole, approved by the Food and Drug Administration in May 2002—and later isavuconazole, approved by the FDA in March 2015.
“Invasive aspergillus often is overlooked, but early diagnosis and treatment are key,” he said. “These are complicated infections with a number of treatment options. Patients really benefit from a multidisciplinary approach, including the expertise of an infectious disease specialist.”
Dr. Patterson led a national committee of the Infectious Diseases Society of America to rewrite the physician guidelines for treating the disease.
The new guidelines, updating guidance from 2008, highlight new methods for diagnosing the infection, as well as new therapies, all based on evidence from clinical trials.
“Because some of the diagnostics are invasive, such as taking a culture directly from the lungs, physicians often are reluctant to proceed. However, because aspergillosis is so deadly, physicians should be aggressive in diagnosing patients suspected of having this infection,” Dr. Patterson said.
With Dr. Patterson’s help, Daniel’s doctors were able to contain the fungus by removing the lower third of his right lung. He recovered from aspergillosis. The 6-foot-3-inch business major at UT Austin is also cancer free.
“I had a lot of trouble regaining my strength, but in the long term, I have not been affected overall,” said Daniel, who continues to get yearly checkups. “It’s definitely not anything I would wish on my worst enemy. It has strengthened me and helped me a lot and helped me help others.”
A first for kids
About 10 percent of childhood cancer can be attributed to genetics. While genomic analysis has been used for some time to identify the risk of inherited cancer in adults, scientists are now using genomic analysis to identify genetic risk factors and to diagnose cancer at an early age in children.
“We are now able to detect which children are most at risk of developing rare pediatric cancers and identify cancers that may have been developing even before the child was born,” said Gail Tomlinson, M.D., Ph.D., professor and interim chair of the Department of Pediatrics.
Dr. Tomlinson is part of a panel of researchers selected by the American Association of Cancer Research to determine—for the first time—international pediatric cancer screening guidelines for more than 50 of the most common syndromes that can develop into pediatric cancer. Dr. Tomlinson contributed to four of the 18 papers published in the association’s journal, Clinical Cancer Research. The series of pediatric cancer screening articles are freely accessible to the public and represent the first comprehensive summary of cancer genetic risks in children.
“Because cancer in children is rare, it’s not practical to screen all children,” Dr. Tomlinson said. “If parents know of relatives who have had multiple pediatric cancers or very early-onset adult cancers, or if we see birth defects in children that are associated with cancer syndromes, genomic analysis can be an excellent risk factor and diagnostic tool.”
Stop breast cancer in its tracks
Researchers are developing a new, first-in-class agent that has stopped the growth of estrogen receptor-positive breast cancer in its tracks.
The new agent, a molecule called ERX-11, has blocked the growth of recurring breast cancer tumors.
“Most breast cancers in women require estrogen or progesterone—the two female hormones—to grow. To treat hormone-dependent cancers, you must either block the hormone or block the receptor that receives the hormone to prevent the development of the cancer,” said Ratna Vadlamudi, Ph.D., professor of obstetrics and gynecology and principal investigator of a study published in the journal eLIFE.
“However, in many patients, tumors become resistant to the current therapy and tumors recur. Our team discovered a new molecule that blocks the estrogen receptor signaling that occurs in resistant tumors and tested a drug based on the molecule in preclinical studies in the lab.”
The drug is expected to be useful in treating breast cancers that are resistant to current therapies, he said.
“Developing this drug is important because it targets a unique site on the estrogen receptor and blocks its interactions with critical proteins that contribute to breast cancer progression,” said Dr. Vadlamudi, who is a member of the Cancer Development & Progression Program at UT Health San Antonio Cancer Center.
Researchers at UT Dallas led by Jung-Mo Ahn, Ph.D., were involved in synthesizing the drug that blocked the interaction, and scientists at UT Southwestern led by Ganesh Raj, M.D., Ph.D., are involved in mechanistic studies and in studies involving primary human breast tumors.
“Implanting mice with the human breast cancer cells usually causes the mice to develop the breast tumors, but when we gave the mice ERX-11 as an oral medication, the cancer growth was dramatically reduced,” Dr. Vadlamudi said. The studies in mice showed no toxic effects, indicating the drug based on the ERX-11 molecule would be a good candidate for human trials.
“The next steps are to synthesize the drug under the FDA’s drug development guidelines and conduct formal toxicity studies to ensure the drug can be safely tolerated,” Dr. Vadlamudi said. “Additional work needs to be done before we can move forward with Phase 1 clinical trials. We expect human trials to begin soon.”
UT Health San Antonio holds a joint patent on the estrogen receptor-positive breast cancer drug with UT Southwestern Medical Center and UT Dallas, with the UT Southwestern Office for Technology Development managing development of the drug.
Clear as water
The lab of Myron Ignatius, Ph.D., is using zebrafish to learn how stem cell biology causes 30 percent of children who have a rare muscle cancer to relapse and not respond to treatment.
These fish have the unusual trait of being translucent.
“Zebrafish are like a glass of water. You can see right through them,” said Dr. Ignatius, assistant professor of molecular medicine at UT Health San Antonio.
This allows researchers to view through a microscope how tumors are born, grow and spread in live animals.
He is first author of a study published in Cell Reports that shows how two signaling pathways work together to establish treatment-resistant secondary tumors that are biologically different from the original tumor.
Rhabdomyosarcoma is a major soft tissue tumor seen in children. Dr. Ignatius’ lab has been able to see secondary rhabdomyosarcoma tumors form in living fish. By labeling cell types with colors—red, yellow, green and purple—they track the progression of stem cells into immature cancer cells and then into mature cancer cells.
Stem cells are prolific and have the versatility to become any type of cell. They also are the only cells that can duplicate themselves. It is thought that only cancer stem cells can make the other types of tumor cells. Stem cells also are the cells most likely to survive cancer treatments and give rise to secondary tumors, Dr. Ignatius said.
Dr. Ignatius and his colleagues found that in rhabdomyosarcoma tumors, cancer stem cells can also be produced by immature cancer cells. Two signaling pathways, NOTCH1 and RAS, collaborate to cause the immature cancer cells to go back a developmental step to become stem cells, where they proliferate to form the new tumors.
“This is very surprising,” Dr. Ignatius said. “The ability to move back a developmental step results in a greater than 20-fold increase in cancer stem cells in the tumors. This is the first time that this phenomenon has been observed in rhabdomyosarcoma. This explains how NOTCH1-expressing tumors can change their biology and become more difficult to treat.”
The researchers confirmed their findings in cells grown in a culture and with tumor samples from patients.
Having defined important pathways that impact tumor growth through this study, Dr. Ignatius is now testing whether inhibiting the NOTCH1 pathway will help patients better fight the disease.