F

or any given medical problem, it seems, there’s a research team trying to use stem cells to find a solution. In clinical trials to treat everything from diabetes to macular degeneration to ALS, researchers are injecting the cells in efforts to cure patients.

But in one study expected to launch later this year, scientists hope to use stem cells in a new, highly controversial way — to reverse death.

The idea of the trial, run by Philadelphia-based Bioquark, is to inject stem cells into the spinal cords of people who have been declared clinically brain-dead. The subjects will also receive an injected protein blend, electrical nerve stimulation, and laser therapy directed at the brain.

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The ultimate goal: to grow new neurons and spur them to connect to each other, and thereby bring the brain back to life.

“It’s our contention that there’s no single magic bullet for this, so to start with a single magic bullet makes no sense. Hence why we have to take a different approach,” said Ira Pastor, CEO of Bioquark.

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, according to Pastor. Regulators shut the study down in November 2016 because, according to Science, India’s Drug Controller General hadn’t cleared it.

(Dr. Himanshu Bansal, who owns the hospital Bioquark was planning to work with in India, disputed Science’s report that the trial had stopped. He said he has been testing the protocol on patients without using Bioquark’s particular peptide mixture and said the results were being observed by an “independent observer” from a local medical college.)

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.”

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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.”

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  • Help my husband is Boston Medical Center and they are telling me he’s brain dead is there any hope for him

  • You must explore applying stem cells to an assume brain dead patient to see if the brain is live but dormant. Think about 16 century bodies buried but a string with bell attached when a person wakes up from a deep alcohol sedation

  • Hello, I’d like to share information I learned during my workplace’s outbreak of an airborne infectious disease that can cause malignancies, precancerous conditions, rheumatological diseases, connective tissue diseases, heart disease, autoimmune symptoms, inflammation in any organ/tissue, seizures, migraines, mood swings, hallucinations, etc. and is often undiagnosed/misdiagnosed in immunocompetent people. Of course, some of it you may already know.

    My coworkers and I, all immunocompetent, got Disseminated Histoplasmosis in Dallas-Fort Worth from roosting bats, the most numerous non-human mammal in the U.S., that shed the fungus in their feces. The doctors said we couldn’t possibly have it, since we all had intact immune systems. The doctors were wrong. Healthy people can get it, too, with widely varying symptoms. And we did not develop immunity over time, we’d get better and then progressively worse, appearing to relapse periodically and concurrently every year.

    More than 100 outbreaks have occurred in the U.S. since 1938, and those are just the ones that were figured out, since people go to different doctors. One outbreak was over 100,000 victims in Indianapolis. 80-90+% of people in some areas have been infected. It can lay dormant for up to 40 years in the lungs and/or adrenals.

    It’s known to cause hematological malignancies, and some doctors claim their leukemia patients go into remission when given antifungal. My friend in another state who died from lupus lived across the street from a bat colony. An acquaintance with alopecia universalis and whose mother had degenerative brain disorder has bat houses on their property.
    There’s too much smoke for there not to be at least a little fire.

    Researchers claim the subacute type is more common than believed. It’s known to at least “mimic” autoimmune diseases and cancer and known to give false-positives in PET scans. But no one diagnosed with an autoimmune disease or cancer is screened for it. In fact, at least one NIH paper states explicitly that all patients diagnosed with sarcoidosis be tested for it, but most, if not all, are not. Other doctors are claiming sarcoidosis IS disseminated histoplasmosis.

    What if this infection, that made me and my coworkers so ill, isn’t rare in immunocompetent people? What if just the diagnosis is rare, since most doctors apparently ignore it? Especially since online documents erroneously state it’s not zoonotic.

    This pathogen parasitizes the reticuloendothelial system/invades macrophages, can infect and affect the lymphatic system and all tissues/organs, causes inflammation and granulomas, etc. It causes idiopathic (unknown cause) diseases and conditions, including hematological malignancies, autoimmune symptoms, myelitis, myositis, vasculitis, panniculitis, dysplasia, hyperplasia, etc. It causes hypervascularization, calcifications, sclerosis, fibrosis, necrosis, eosinophilia, leukopenia, anemia, neutrophilia, pancytopenia, thrombocytopenia, hypoglycemia, cysts, abscesses, polyps, stenosis, perforations, GI problems, hepatitis, focal neurologic deficits, etc.

    Many diseases it might cause are comorbid with other diseases it might cause, for example depression/anxiety/MS linked to Crohn’s.

    The fungus is an Oxygenale and therefore consumes collagen. It’s known to cause connective tissue diseases (Myxomatous degeneration?), rheumatological conditions, seizures, and mental illness. Fungal hyphae carry an electrical charge and align under a current. It causes RNA/DNA damage. It’s known to cause delusions, wild mood swings (pseudobulbar affect?), and hallucinations. It’s most potent in female lactating bats, because the fungus likes sugar (lactose) and nitrogen (amino acids, protein, neurotransmitters?). What about female lactating humans…postpartum psychosis (and don’t some of these poor women also have trouble swallowing)? The bats give birth late spring/summer, and I noticed suicide rates spike in late spring/early summer. It’s known to cause retinal detachment, and retinal detachments are known to peak around June-July/in hot weather. A map of mental distress and some diseases appear to almost perfectly overlay a map of Histoplasmosis. Johns Hopkins linked autism to an immune response in the womb. Alzheimer’s was linked to hypoglycemia, which can be caused by chronic CNS histoplasmosis. The bats eat moths, which are attracted to blue and white city lights that simulate the moon the moths use to navigate. Bats feed up to 500 feet in the air and six miles away in any direction from their roost, but not when it’s raining or when the temperature is less than approximately 56° F.

    I believe the “side effects” of Haldol (leukopenia and MS symptoms) might not always be side effects but just more symptoms of Disseminated Histoplasmosis, since it causes leukopenia and MS symptoms. What about the unknown reason why beta receptor blockers cause tardive dyskinesia? The tinnitus, photophobia, psychosis “caused” by Cipro? Hypersexuality and leukemia “caused” by Abilify? Humira linked to lymphoma, leukemia and melanoma in children? Disseminated Histoplasmosis is known to cause enteropathy, so could some people thought to have nonsteroidal anti-inflammatory drug enteropathy have it and taking NSAIDs for the pain/inflammation it causes, and the NSAIDs aren’t the actual culprit?

    From my experience, I learned that NO doctor, at least in DFW, will suspect subacute and/or progressive disseminated histoplasmosis in immunocompetent people. Some doctors, at least the ones I went to, will actually REFUSE to test for it, even when told someone and their coworkers have all the symptoms and spend a lot of time in a building with bats in the ceiling. Victims will be accused of hypochondriasis. In fact, the first doctor to diagnose me was a pulmonologist, and the only reason he examined me was to try to prove that I didn’t have it, when I really did. No doctor I went to realized bats carry the fungus. And NO doctor I went to in DFW, even infectious disease “experts,” understand the DISSEMINATED form, just the pulmonary form, and the only test that will be done by many doctors before they diagnose people as NOT having it is an X-ray, even though at least 40-70% of victims will have NO sign of it on a lung X-ray. It OFTEN gives false-negatives in lab tests (some people are correctly diagnosed only during an autopsy after obtaining negative test results) and cultures may not show growth until after 12 weeks of incubation (but some labs report results after 2 weeks).

    One disease of unknown cause that could be caused by Disseminated Histoplasmosis: I suspect, based on my and my coworker’s symptoms (during our “rare” infectious disease outbreak) and my research, that interstitial cystitis and its comorbid conditions can be caused by disseminated histoplasmosis, which causes inflammation throughout the body, causes “autoimmune” symptoms, and is not as rare as believed. I read that “interstitial cystitis (IC) is a chronic inflammatory condition of the submucosal and muscular layers of the bladder, and the cause is currently unknown. Some people with IC have been diagnosed with other conditions such as irritable bowel syndrome (IBS), fibromyalgia, chronic fatigue syndrome, allergies, and Sjogren’s syndrome, which raises the possibility that interstitial cystitis may be caused by mechanisms that cause these other conditions. In addition, men with IC are frequently diagnosed as having chronic nonbacterial prostatitis, and there is an extensive overlap of symptoms and treatment between the two conditions, leading researchers to posit that the conditions may share the same etiology and pathology.” Sounds like Disseminated Histoplasmosis, doesn’t it?

    My coworkers and I were always most ill around April/May/June, presumably since the Mexican Free-tail bats gave birth in Texas during May, and fall/Thanksgiving to December, for some unknown reason (maybe migrating bats from the north?). We had GI problems, liver problems, weird rashes (erythema nodosum, erythema multiforme, erythema annulare, etc.), plantar fasciitis, etc., and I had swollen lymph nodes, hives, lesions, abdominal aura, and started getting migraines and plantar fasciitis in the building, and I haven’t had them since I left. It gave me temporary fecal incontinence, seizures, dark blood from my intestines, tinnitus, nystagmus, benign paroxysmal positional vertigo, what felt like burning skin, various aches and pains (some felt like pin pricks and pinches), tingling, tremors, “explosions” like fireworks in my head while sleeping, temporary blindness, and chronic spontaneous “orgasms”/convulsions. Suddenly I was allergic to pears (latex fruit allergy?). I had insomnia (presumably from the fungus acidifying the blood, releasing adrenaline) and parasomnias. I suddenly had symptoms of several inflammatory/autoimmune diseases, including Fibromyalgia, Sarcoidosis, ALS, MS, Sjogren’s syndrome, etc. that have disappeared since leaving the area and taking nothing but Itraconazole antifungal.

    No one, including doctors (we all went to different ones), could figure out what was wrong with us, and I was being killed by my doctor, who mistakenly refused to believe I had it and gave me progressively higher and higher doses of Prednisone (at least 2 years after I already had Disseminated Histoplasmosis) after a positive ANA titer, until I miraculously remembered that a visiting man once told my elementary school class that bats CARRY histoplasmosis….so much of it that they evolved to deal with the photophobia and tinnitus it causes by hunting at night by echolocation. There’s a lot more. I wrote a book about my experience with Disseminated Histoplasmosis called “Batsh#t Crazy,” because bats shed the fungus in their feces and it causes delusions and hallucinations, I suspect by the sclerotia it can form emitting hallucinogens (like psilocybin and dimethyltryptamine) along with inflammation in the CNS. (Schizophrenics have 2X of a chemical associated with yeast, part of the fungal life cycle.)

    Thank you for your time,

    Susan McIntyre

  • I and my colleagues live in an underground base in the Florida Everglades and are completely surrounded by the walking dead who want nothing more than to eat us for some odd reason. The year is 1985 and I’m wondering if it was you lot who made all these ‘dead ‘un’s outside my bloody fences!

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