BRAINCONTROLLED EXOSKELETON IN CLINICAL TRIALS

BY LAURIE FICKMAN

When 66-year-old Oswald Reedus had a stroke in 2014, he became one of 795,000 people in the United States who annually suffer the same fate. This year he also became the first stroke patient in the world to use a robotic arm controlled by his brainwaves - at home - to recover the use of a limb.

In the war against cancer, one of the most critical battles is waged on a cellular level as T cells from the immune system are altered in the lab to attack cancer cells. This form of immunotherapy, called chimeric antigen receptor (CAR) T-cell therapy, can be a life-saving treatment resulting in tumor control lasting ten years or longer.

Now an engineer at the University of Houston has found a way to determine which patients are likely to respond to CAR T-cell therapy, saving precious time in treating lymphoma, which is most responsive to this form of immunotherapy. It’s valuable knowledge to have since not all patients respond to the therapy, and some experience severe side effects.

To determine the best patient prospects, Navin

Varadarajan, M.D. Anderson Professor of Chemical and Biomolecular Engi-

Varadarajan and his partners at The University of Texas MD Anderson Cancer Center profiled the dynamic interactions between T cells that comprise patient infusion products and tumors, using the TIMING (Timelapse Imaging Microscopy In Nanowell Grids) method, developed in Varadarajan’s lab at UH. TIMING is high-throughput single-cell technology that merges artificial intelligence with a nanowell imaging platform to simultaneously evaluate how individual cells move, activate, interact, kill and survive.

By interrogating thousands of individual interactions between T cells and tumor cells, the research team identified the important interaction between CD2 and CD58. To translate the results back to the clinic, Varadarajan and Dr. Sattva Neelapu from MD Anderson, stained the tumors obtained before initiation of treatment. That’s how the group was able to show that patients whose tumors expressed CD58 are much more likely to respond to CAR T cell therapy compared to patients whose tumors did not express CD58.

Reedus was lucky to live in Houston and have access to this futuristic-looking, portable device - an invention of Cullen College of Engineering professor Jose Luis Contreras-Vidal an international pioneer in noninvasive brain-machine interfaces and robotic device inventions. His team developed the portable brain-computer interface (BCI) exoskeleton to restore upper limb function.

It’s the next generation of stroke rehabilitation, and now Reedus’ name will forever be associated with it. “If I can pass along anything to help a stroke person’s life, I will do it. For me it’s my purpose in life now,” said Reedus, whose determination sharpened after his mother and younger brother both died of strokes.

Reedus realized he had lost the use of his left arm the night he had the stroke. His wife roused him from sleep, asking him to get up because he was mumbling, and she couldn’t understand his words. He tried but couldn’t use his left arm to help him rise. The stroke also caused Reedus to suffer aphasia, a difficulty with speech, barely noticeable now. “I don’t know why God spared me, but I want to leave here helping someone,” he said.

Now he’s helping usher in a pivotal moment in stroke rehabilitation and medical science. Goal achieved.

Using the Robot

Most neuro technologies are limited to the lab or clinic and are very expensive and hard to operate. This brain-controlled robotic arm requires no surgery and is accessible to robotically guide stroke rehabilitation both in clinic and at home. Reedus’ use of it in his Houston home follows clinical trials at TIRR Memorial Hermann.

“The broader impact and commercial potential of this project is to advance national health by accelerating development, efficacy and use of brain-controlled robotic rehabilitation after stroke by capitalizing on the benefits of non-invasive brain interfaces that extract information about the patient’s motor intent and the real-time assessment of impairment and recovery of motor function," said Contreras-Vidal, Hugh Roy and Lillie Cranz Cullen Distinguished Professor of Electrical and Computer Engineering at UH.

“Brain-machine interfaces based on scalp electroencephalography (EEG) have the potential to promote cortical plasticity following stroke, which has been shown to improve motor recovery outcomes.”

Neuroplasticity is the brain’s ability to modify, change, adapt and recover itself. Like a plastic material, which can be stretched and shaped to a desired design, there are certain properties in the brain that induce flexibility to recover even decades after a stroke or brain injury.

Advancing National Health

The promise of advancing national health is no understatement. Stroke is the leading cause of neurological disability in the United States and arm paresis is a primary cause of physical disability, yet only 31 percent of stroke survivors receive outpatient rehabilitation.

"Our project addresses a pressing need for accessible, safe and effective stroke rehabilitation devices for in-clinic and at-home use for sustainable long-term therapy, a global market size expected to currently be $31 billion. Unfortunately, current devices fail to engage the patients, are hard to match to their needs and capabilities, are costly to use and maintain, or are limited to clinical settings,” said Contreras-Vidal.

His brain-controlled robotic devices are excellent candidates for engaging patients and delivering the repetitive and intensive practice stroke survivors require for rehabilitation.

It’s a medical milestone that certainly takes a village.

The project is funded by an $813,999 grant from the National Science Foundation’s newly created Division of Translational Impacts, TIP Directorate for Tech, Innovation, & Partnerships. Contreras-Vidal is director of the NSF-funded IUCRC BRAIN Center and the Laboratory for Noninvasive Brain-Machine Interface Systems at UH where he developed the device. Gerard E. Francisco, M.D., chair and professor in the Department of Physical Medicine and Rehabilitation at McGovern Medical School at UTHealth Houston and chief medical officer and director of the Neuro Recovery Research Center at TIRR Memorial Hermann, is leading the clinical trials.

“This is truly exciting because what we know now is there are so many ways we can induce neuroplasticity or how we can boost recovery,” said Francisco, who said TIRR is wise to partner with engineering schools such as the Cullen College of Engineering