But the scientific literature — scarce as it is — seems to show that even several magic bullets are unlikely to accomplish what Bioquark hopes it will.
This isn’t the first start for the trial. The study launched in Rudrapur, India, in April 2016 — but it never enrolled any patients. Regulators shut the study down in November 2016 because, according to Science, India’s Drug Controller General hadn’t cleared it.
Now, Pastor said, the company is in the final stages of finding a new location to host trials. The company will announce a trial in Latin America in coming months, Pastor told STAT.
If that trial mirrors the protocol for the halted Indian one, it’ll aim to enroll 20 patients who’ll receive a barrage of treatments. First there’s the injection of stem cells isolated from the individual’s own fat or blood. Second, there’s a peptide formula injected into the spinal cord, purported to help nurture new neurons’ growth. (The company has tested the same concoction, called BQ-A, in animal models of melanoma, traumatic brain injuries, and skin wrinkling.) Third, there’s a regimen of nerve stimulation and laser therapy over 15 days to spur the neurons to form connections. Researchers will look to behavior and EEG for signs that the treatment is working.
But the process is fraught with questions. How do researchers complete trial paperwork when the person participating is, legally, dead? (In the United States, state laws most often define death as the irreversible loss of heart and lung or brain function.) If the person did regain brain activity, what kind of functional abilities would he or she have? Are families getting their hopes up for an incredibly long-shot cure?
Answers to most of those questions are still far off. “Of course, many folks are asking the ‘what comes next?’ question,” Pastor acknowledged. “While full recovery in such patients is indeed a long term vision of ours, and a possibility that we foresee with continued work along this path, it is not the core focus or primary endpoint of this first protocol.”
Simply quirky or mostly quackery?
No real template exists to know whether this approach might work — and it’s gotten some prominent backlash. Neurologist Dr. Ariane Lewis and bioethicist Arthur Caplan wrote in a 2016 editorial that the trial “borders on quackery,” “has no scientific foundation,” and gave families “a cruel, false hope for recovery.” (“Exploratory research programs of this nature are not false hope. They are a glimmer of hope,” Pastor responded.)
The company hasn’t tested the full, four-pronged treatment, even in animal models. Studies have evaluated the treatments singly for other conditions — stroke, coma — but brain death is a quite different proposition.
Stem cell injections to the brain or spinal cord have shown some positive results for children with brain injuries; trials using similar procedures to treat cerebral palsy and ALS have also been completed. One small, uncontrolled study of 21 stroke patients found that they recovered more mobility after they received an injection of donor stem cells into their brains.
On transcranial laser devices, the evidence is mixed. The approach has been shown to stimulate neuron growth in some animal studies. However, a high-profile Phase 3 study of one such device in humans was halted in 2014 after it showed no effect on 600 patients’ physical capabilities as they recovered from a stroke. Other trials to revive people from comas using laser therapy are underway.
The literature around electrical stimulation of the median nerve — which branches from the spinal cord down the arm and to the fingers — primarily consists of case studies. Dr. Ed Cooper wrote some of those papers, one of which described dozens of patients treated in his home state of North Carolina, including 12 who had a Glasgow Coma Score of 4 — an extremely low score on the scale. With time (and with the nerve stimulation), four of those 12 people made a “good recovery,” the paper described; others were left with minor or major disabilities after their coma.
But Cooper, an orthopedic surgeon by training who worked with neurosurgeons on the paper, said unequivocally that there is no way this technique could work on someone who is brain-dead. The technique, he said, relies on there being a functional brain stem — one of the structures that most motor neurons go through before connecting with the cortex proper. If there’s no functional brain stem, then it can’t work.
Pastor agreed — but he claimed the technique would work because there are “a small nest of cells” that still function in patients who are brain-dead.
Complicating such trials, there is no clear-cut confirmatory test for brain death — meaning a recovery in the trial might not be entirely due to the treatment. Some poisons and drugs, for instance, can make people look brain-dead. Bioquark plans to rely on local physicians in the trial’s host country to make the declaration. “We’re not doing the confirmatory work ourselves,” Pastor said, but each participant would have undergone a battery of tests considered appropriate by local authorities.
But a survey of 38 papers published over 13 years found that, if the American Academy of Neurology guidelines for brain death had been met, no brain-dead people have ever regained brain function.
Of Bioquark’s full protocol, “it’s not the absolute craziest thing I’ve ever heard, but I think the probability of that working is next to zero,” said Dr. Charles Cox, a pediatric surgeon who has done research with mesenchymal stem cells — the type used in the trial — at the University of Texas Health Science Center at Houston. Cox is not involved in Bioquark’s work.
Some studies have found that cells from a part of the brain called the subventricular zone can grow in culture even after a person is declared dead, Cox said. However, it’s unlikely that the trial’s intended outcome — to have a stem cell treatment result in new neurons or connections — would actually happen. Neurons would likely struggle to survive, because blood flow to the brain is almost always lost in people who have been declared brain-dead, Cox said.
But Pastor thinks Bioquark’s protocol will work. “I give us a pretty good chance,” he said. “I just think it’s a matter of putting it all together and getting the right people and the right minds on it.”
Cox is less optimistic. “I think [someone reviving] would technically be a miracle,” he said. “I think the pope would technically call that a miracle.”