Researchers from Baylor College of Medicine and the University of Houston have developed a new blood-filtering machine that poses fewer risks to pediatric patients with hyperleukocytosis. Photo courtesy UH.

A team of Houston researchers has developed a new microfluidic device aimed at making treatments safer for children with hyperleukocytosis, a life-threatening hematologic emergency often seen in patients with leukemia.

Dr. Fong Lam, an associate professor of pediatrics at Baylor College of Medicine and a pediatric intensive care physician at Texas Children’s Hospital, partnered with Sergey Shevkoplyas, a professor of biomedical engineering at UH, on the device that uses a large number of tiny channels to quickly separate blood cells by size in a process called controlled incremental filtration, according to a news release from UH.

They tested whether performing cell separation with a high-throughput microfluidic device could alleviate the limitations of traditional conventional blood-filtering machines, which pose risks for pediatric patients due to their large extracorporeal volume (ECV), high flow rates and tendency to cause significant platelet loss in the patient. The results of their study, led by Mubasher Iqbal, a Ph.D. candidate in biomedical engineering at UH, were published recently in the journal Nature Communications.

“Continuously and efficiently separating leukocytes from recirculating undiluted whole blood — without device clogging and cell activation or damage — has long been a major challenge in microfluidic cell separation,” Shevkoplyas said in a news release. “Our study is the first to solve this problem.”

Hyperleukocytosis is a condition that develops when the body has an extremely high number of white blood cells, which in many cases is due to leukemia. According to the release, up to 20 percent to 30 percent of patients with acute leukemia develop hyperleukocytosis, and this places them at risk for potentially fatal complications.

The new device utilizes tiny channels—each about the width of a human hair—to efficiently separate blood cells through controlled incremental filtration. According to Lam, the team was excited that the new device could operate at clinically relevant flow rates.

The device successfully removed approximately 85 percent of large leukocytes and 90 percent of leukemic blasts from undiluted human whole blood without causing platelet loss or other adverse effects. It also operates with an ECV that’s about 1/70th of conventional leukapheresis machines, which makes it particularly suitable for infants and small children.

“Overall, our study suggests that microfluidics leukapheresis is safe and effective at selectively removing leukocytes from circulation, with separation performance sufficiently high to ultimately enable safe leukapheresis in children,” Shevkoplyas said in the release.

A team of researchers at the University of Houston is working to develop a new treatment for Rhabdomyosarcoma, an aggressive cancer with a higher incidence in young children. Photo via Getty Images.

UH research team receives grant to fight aggressive pediatric cancer

cancer research

Researchers at the University of Houston have received a $3.2 million grant from the National Institutes of Health to help find innovative ways to treat Rhabdomyosarcoma, or RMS.

According to a statement from the university, RMS is a malignant soft tissue sarcoma that has a higher incidence in young children and is responsible for 8 percent of pediatric cancer cases with a relatively low survival rate.

One way UH is working on the issue is by studying how and why RMS cells, which are found most often in muscle tissue, divide uncontrollably without ever maturing into normal muscle cells. The researchers aim to tackle a target inside RMS cells known as TAK1, which plays a key role in regulating cell growth.

“By targeting TAK1, we aim to stop the cancer at its source and help the cells develop normally,” Ashok Kumar, the Else and Philip Hargrove Endowed Professor of Drug Discovery at the UH College of Pharmacy and director of the Institute of Muscle Biology and Cachexia, said in a news release. “This approach could lead to new and better treatments for RMS.”

According to UH, preliminary results demonstrated that TAK1 is highly activated in embryonal RMS cells, which are found in younger children; alveolar RMS cells, which are found in older children and teens; and human RMS samples. This suggests that the protein plays a major role in the development of this form of cancer.

The team still aims to uncover how the protein helps RMS cancer grow and plans to evaluate how blocking TAK1 can be used as a therapeutic.

“Blocking TAK1, either by changing the genes (genetic approaches) or using drugs (pharmacological approaches), can stop certain harmful behaviors in cancer cells,” Kumar added. “This was tested both in lab-grown cells and in living models, showing that TAK1 is a key target to control RMS cancer’s spread and aggressiveness, and inhibits tumor formation.”

Allterum Therapeutics Inc., a portfolio company of Fannin Innovation Studio, is using the funds to prepare for clinical trials. Photo via Getty Images

Houston biotech startup raises millions to battle pediatric cancer

fresh funds

Allterum Therapeutics Inc. has built a healthy launchpad for clinical trials of an immunotherapy being developed to fight a rare form of pediatric cancer.

The Houston startup recently collected $1.8 million in seed funding through an investor group associated with Houston-based Fannin Innovation Studio, which focuses on commercializing biotech and medtech discoveries. Allterum has also brought aboard pediatric oncologist Dr. Philip Breitfeld as its chief medical officer. And the startup, a Fannin spinout, has received a $2.9 million grant from the Cancer Prevention Research Institute of Texas.

The funding and Breitfeld's expertise will help Allterum prepare for clinical trials of 4A10, a monoclonal antibody therapy for treatment of cancers that "express" the interleukin-7 receptor (IL7R) gene. These cancers include pediatric acute lymphoblastic leukemia (ALL) and some solid-tumor diseases. The U.S. Food and Drug Administration (FDA) has granted "orphan drug" and "rare pediatric disease" designations to Allterum's monoclonal antibody therapy.

If the phrase "monoclonal antibody therapy" sounds familiar, that's because the FDA has authorized emergency use of this therapy for treatment of COVID-19. In early January, the National Institute of Allergy and Infectious Diseases announced the start of a large-scale clinical trial to evaluate monoclonal antibody therapy for treatment of mild and moderate cases of COVID-19.

Fannin Innovation Studio holds exclusive licensing for Allterum's antibody therapy, developed at the National Cancer Institute. Aside from the cancer institute, Allterum's partners in advancing this technology include the Therapeutic Alliance for Children's Leukemia, Baylor College of Medicine, Texas Children's Hospital, Children's Oncology Group, and Leukemia & Lymphoma Society.

Although many pediatric patients with ALL respond well to standard chemotherapy, some patients continue to grapple with the disease. In particular, patients whose T-cell ALL has returned don't have effective standard therapies available to them. Similarly, patients with one type of B-cell ALL may not benefit from current therapies. Allterum's antibody therapy is designed to effectively treat those patients.

Later this year, Allterum plans to seek FDA approval to proceed with concurrent first- and second-phase clinical trials for its immunotherapy, says Dr. Atul Varadhachary, managing partner of Fannin Innovation Studio, and president and CEO of Allterum. The cash Allterum has on hand now will go toward pretrial work. That will include the manufacturing of the antibody therapy by Japan's Fujifilm Diosynth Biotechnologies, which operates a facility in College Station.

"The process of making a monoclonal antibody ready to give to patients is actually quite expensive," says Varadhachary, adding that Allterum will need to raise more money to carry out the clinical trials.

The global market for monoclonal antibody therapies is projected to exceed $350 billion by 2027, Fortune Business Insight says. The continued growth of these products "is expected to be a major driver of overall biopharmaceutical product sales," according to a review published last year in the Journal of Biomedical Science.

One benefit of these antibody therapies, delivered through IV-delivered infusions, is that they tend to cause fewer side effects than chemotherapy drugs, the American Cancer Society says.

"Monoclonal antibodies are laboratory-produced molecules engineered to serve as substitute antibodies that can restore, enhance or mimic the immune system's attack on cancer cells. They are designed to bind to antigens that are generally more numerous on the surface of cancer cells than healthy cells," the Mayo Clinic says.

Varadhachary says that unlike chemotherapy, monoclonal antibody therapy takes aim at specific targets. Therefore, monoclonal antibody therapy typically doesn't broadly harm healthy cells the way chemotherapy does.

Allterum's clinical trials initially will involve children with ALL, he says, but eventually will pivot to children and adults with other kinds of cancer. Varadhachary believes the initial trials may be the first cancer therapy trials to ever start with children.

"Our collaborators are excited about that because, more often than not, the cancer drugs for children are ones that were first developed for adults and then you extend them to children," he says. "We're quite pleased to be able to do something that's going to be important to children."

Ad Placement 300x100
Ad Placement 300x600

CultureMap Emails are Awesome

How Houston innovators played a role in the historic Artemis II splashdown

safe landing

Research from Rice University played a critical role in the safe return of U.S. astronauts aboard NASA’s Artemis II mission this month.

Rice mechanical engineer Tayfun E. Tezduyar and longtime collaborator Kenji Takizawa developed a key computational parachute fluid-structure interaction (FSI) analysis system that proved vital in NASA’s Orion capsule’s descent into the Pacific Ocean. The FSI system, originally developed in 2013 alongside NASA Johnson Space Center, was critical in Orion’s three-parachute design, which slowed the capsule as it returned to Earth, according to Rice.

The model helped ensure that the parachute design was large enough to slow the capsule for a safe landing while also being stable enough to prevent the capsule from oscillating as it descended.

“You cannot separate the aerodynamics from the structural dynamics,” Tezduyar said in a news release. “They influence each other continuously and even more so for large spacecraft parachutes, so the analysis must capture that interaction in a robustly coupled way.”

The end result was a final parachute system, refined through NASA drop tests and Rice’s computational FSI analysis, that eliminated fluctuations and produced a stable descent profile.

Apart from the dynamic challenges in design, modeling Orion’s parachutes also required solving complex equations that considered airflow and fabric deformation and accounted for features like ringsail canopy construction and aerodynamic interactions among multiple parachutes in a cluster.

“Essentially, my entire group was dedicated to that work, because I considered it a national priority,” Tezduyar added in the release. “Kenji and I were personally involved in every computer simulation. Some of the best graduate students and research associates I met in my career worked on the project, creating unique, first-of-its-kind parachute computer simulations, one after the other.”

Current Intuitive Machines engineer Mario Romero also worked on Orion during his time at NASA. From 2018 to 2021, Romero was a member of the Orion Crew Capsule Recovery Team, which focused on creating likely scenarios that crewmembers could encounter in Orion.

The team trained in NASA’s 6.2-million-gallon pool, using wave machines to replicate a range of sea conditions. They also simulated worst-case scenarios by cutting the lights, blasting high-powered fans and tipping a mock capsule to mimic distress situations. In some drills, mock crew members were treated as “injured,” requiring the team to practice safe, controlled egress procedures.

“It’s hard to find the appropriate descriptors that can fully encapsulate the feeling of getting to witness all the work we, and everyone else, did being put into action,” Romero tells InnovationMap. “I loved seeing the reactions of everyone, but especially of the Houston communities—that brought me a real sense of gratitude and joy.”

Intuitive Machines was also selected to support the Artemis II mission using its Space Data Network and ground station infrastructure. The company monitored radio signals sent from the Orion spacecraft and used Doppler measurements to help determine the spacecraft's precise position and speed.

Tim Crain, Chief Technology Officer at Intuitive Machines, wrote about the experience last week.

"I specialized in orbital mechanics and deep space navigation in graduate school,” Crain shared. “But seeing the theory behind tracking spacecraft come to life as they thread through planetary gravity fields on ultra-precise trajectories still seems like magic."

UH breakthrough moves superconductivity closer to real-world use

Energy Breakthrough

University of Houston researchers have set a new benchmark in the field of superconductivity.

Researchers from the UH physics department and the Texas Center for Superconductivity (TcSUH) have broken the transition temperature record for superconductivity at ambient pressure. The accomplishment could lead to more efficient ways to generate, transmit and store energy, which researchers believe could improve power grids, medical technologies and energy systems by enabling electricity to flow without resistance, according to a release from UH.

To break the record, UH researchers achieved a transition temperature 151 Kelvin, which is the highest ever recorded at ambient pressure since the discovery of superconductivity in 1911.

The transition temperature represents the point just before a material becomes superconducting, where electricity can flow through it without resistance. Scientists have been working for decades to push transition temperature closer to room temperature, which would make superconducting technologies more practical and affordable.

Currently, most superconductors must be cooled to extremely low temperatures, making them more expensive and difficult to operate.

UH physicists Ching-Wu Chu and Liangzi Deng published the research in the Proceedings of the National Academy of Sciences earlier this month. It was funded by Intellectual Ventures and the state of Texas via TcSUH and other foundations. Chu, founding director and chief scientist at TcSUH, previously made the breakthrough discovery that the material YBCO reaches superconductivity at minus 93 K in 1987. This helped begin a global competition to develop high-temperature superconductors.

“Transmitting electricity in the grid loses about 8% of the electricity,” Chu, who’s also a professor of physics at UH and the paper’s senior author, said in a news release. “If we conserve that energy, that’s billions of dollars of savings and it also saves us lots of effort and reduces environmental impacts.”

Chu and his team used a technique known as pressure quenching, which has been adapted from techniques used to create diamonds. With pressure quenching, researchers first apply intense pressure to the material to enhance its superconducting properties and raise its transition temperature.

Next, researchers are targeting ambient-pressure, room-temperature superconductivity of around 300 K. In a companion PNAS paper, Chu and Deng point to pressure quenching as a promising approach to help bridge the gap between current results and that goal.

“Room-temperature superconductivity has been seen as a ‘holy grail’ by scientists for over a century,” Rohit Prasankumar, director of superconductivity research at Intellectual Ventures, said in the release. “The UH team’s result shows that this goal is closer than ever before. However, the distance between the new record set in this study and room temperature is still about 140 C. Closing this gap will require concerted, intentional efforts by the broader scientific community, including materials scientists, chemists, and engineers, as well as physicists.”

---

This article originally appeared on EnergyCapitalHTX.com.