The Noonan Report
Back in the year 2019, when Covid was merely a nasty rumor floating in from China, a friend of The Flying Pie was delivered even worse health news. Captain Noonan, a 70-year-old multimillionaire aviator with his own Batcave (or maybe it’s an airplane hangar) was diagnosed with Amyotrophic Lateral Sclerosis, a muscle-wasting disease made famous by the victimization of baseball legend Lou Gehrig in June of 1939. The Captain did what everyone else does in such circumstances---he refused to believe it. Believing it meant conceding you were taking the Ultimate Flight in short order, weighed down by failing muscles and eventual paralysis while your brain took it all in from the control tower. The average time remaining to ALS victims is three fright-filled years from diagnosis, most of it in the same swaddled armchair.
ALS attacks nerve cells called motor neurons that control voluntary muscles, the ones we can control. When these nerve cells die, voluntary muscle control and movement are lost. This leads to progressive weakness and disability. People with ALS eventually lose their strength, ability to move their arms, legs and body, then the ability to breathe on their own. In the great majority of cases, their minds remain sharp and alert. Death usually comes two to five years after diagnosis but Amyotrophic Lateral Sclerosis is a variable disease that progresses at different rates for different people. Steven Hawking, the ultimate outlier, lived til age 76, though in extreme discomfort. He was fairly wealthy and you’re not.
What Can You Do But Spit In Your Hat?
At approximately the same time Captain Noonan was struck down by ALS, one Sean M. Healy, CEO of Affiliated Managers Group got the same awful diagnosis. Not one to dwell on bad news, Healy immediately counterattacked, endowing Massachusetts General Hospital and its chief of Neurology Merit Cudkowicz with a whopping $40 million transformative gift to immediately pursue “a revolutionary approach to research and care for ALS.” It was the third largest gift in the hospital’s history but bore little immediate fruit. Healy was dead at age 59 by May of 2020.
Captain Noonan also made a visit to Mass. General and the affiliated ALS Society across the river in Cambridge. Unsatisfied that any current research would gallop to his rescue in time, he called upon his friend Dr. Siobhan Ellison, who had developed a drug to successfully combat the horse ailment Equine Protozoal Myeloencephalitis. Over the next several months, Ellison located and assembled into a panel a dozen of the leading ALS researchers in the country. The group, funded by Noonan, communicated via Zoom meetings, exchanged information and explored new avenues to arrest or at least slow down Amyotrophic Lateral Sclerosis. All the while, the Captain continued to regress, albeit slowly, a prisoner of Fate in his lavish castle.
Then, after four years of exploration and tinkering, Ellison plunked her magic twanger and came up with a promising new drug she calls TVALA. Early experiments with the invention have been encouraging. According to Siobhan, “TVALA is a retro-enantomer of a natural hormone that regulates inflammation in the body. The hormone has a brief half-life and hasn’t been an effective therapeutic in spite of efforts to make one for several diseases in the last 40 years. TVALA uses a trick to make it last longer---we reversed the five amino acid sequence and used ‘D’ instead of the natural ‘L’ configuration that the body recognizes. The result is a six-hour half-life and the possibility to slow down ALS.”
Is it possible that after all these years of misery and wretched deaths that a veterinarian/scientist working in her small home laboratory in Fairfield, Florida can pull off a miracle the combined opponents of ALS have struggled to discover in over a century? Stay tuned, TVALA will be subjected to a study in humans in the next few months. Captain Noonan is hanging on for dear life but he is smiling a lot more often these days.
Messin’ With MS
According to the federal government’s National Institute of Neurological Disorders and Stroke, nearly 3 million people worldwide (with almost one-third in the U.S.) are living with multiple sclerosis, a disabling neurological disease in which the body’s immune system mistakenly attacks nerves feeding information to the central nervous system---the brain and the spinal cord. Although rarely fatal, MS can lead to long-term disabilities and impair movement, muscle control, vision and cognition. It’s one thing when 3 million anonymous parties contract the disease, you pay more attention when a few of your friends get smacked broadside.
There currently is no cure for MS and nobody expected one anytime soon. However, new findings from a recent Johns Hopkins Medicine study (from the journal Science Advances) provide strong support for a promising advance toward that goal. Researchers may soon have the ability to reverse and even completely alleviate MS-like symptoms in mice.
For an unknown reason in people with MS, some of the body’s first line of defense against foreign invaders---immune cells known as CD4+ T-cells---fail to recognize that myelin, the fatty material surrounding and protecting nerve cells, is a normal part of the human system. If these wayward T-cells become dominant, they can provoke inflammation that damages or destroys the myelin sheath, which in turn can severely disrupt or curtail transmission of nerve impulses from all parts of the body to the brain.
“We developed a method for tipping the balance of the T-cells reaching the central nervous system from effectors to regulatory T-cells that modulate the immune system and have been shown to prevent autoimmune reactions,” says study co-author Giorgio Raimondi, associate director of the Vascularized Composite Allotransplantation Research Laboratory at Johns Hopkins School of Medicine.
“Using this therapy on mice bred to exhibit symptoms modeling those seen in humans with MS, we found we could enhance the growth of T-regs while simultaneously reducing the number of effectors, resulting in reversal of the MS-like symptoms in 100% of the mice. And even more exciting, achieving a full recovery in 38%.”
Hear that, Tom and Teresa? Pretty soon you’ll be dancing the Texas Two-Step in the aisles at the Hogtown Opry. Watch out for Thacker, he’s still in his Bossa Nova stage.
Elsewhere On The Battlefront
Roger Albin, a professor of neurology and co-director of the Movement Disorders Clinic in the Department of Neurology at the University of Michigan Medical School reports that the current Diabetes drug Exenatide is now in a phase 3 trial for use in victims of Parkinson’s disease. The drug had reasonable preclinical data and some promising phase 2 data, which in the Parkinson’s world where there is not an animal model for great predictive validity is about as good as it gets. The medical community is looking for unequivocal results, whether positive or negative. A clear positive result would be grounds for confetti but a clear negative response is actually just as important.
Robert Coleman, the chief scientific officer at US Oncology Research, claims the most imminent and important upcoming trial result expected in his field in 2023 involves Mirvetuximab Soravtansine from ImmunoGen. The drug received accelerated approval from the US Food and Drug Administration on November 14 based on results of a single-arm trial that enrolled 106 patients with platinum-resistant ovarian cancer whose tumors had high expression of folate receptor-a and who had been treated with up to three prior regimens, at least one of which included Avastin.
Simone Spuler, leader of a myology research group at a prominent clinic in Germany advises that muscle stem cells are the only cells that can regenerate muscle. In patients who have a genetic muscular dystrophy in which muscle wastes for genetic reasons, these stem cells carry mutations, and these mutations can now be corrected with CRISPR—Cas9 and other tools Correcting muscle cells means muscles can be rebuilt, which has not been previously possible. Muscular dystrophies are a group of approximately 50 different diseases that lead young people and children to lose their ability to walk or even breathe, leaving them wheelchair-bound within a couple of years. Spuler’s group began treating students in June and expect a critical date within a few months.
Alan Levey, a professor and chair of the Department of Neurology at Emory University’s School of Medicine and director of the EU Goizueta Alzheimer’s Disease Research Center, is examining data on Lecanemab, an investigational monoclonal antibody to amyloid-b protofibrils, for the treatment of mild cognitive impairment with Alzheimer’s disease. The developer, Eisai, announced positive topline results from a large global phase 3 clinical trial in September. The company is expected to file an application with the FDA for traditional approval in the U.S. by summer of this year.
Anssi Auvinen, a professor of health services at Tampere University in Finland, is concerned that the evidence surrounding testing for the marker PSA is full of conflict since the test may detect prostate cancer at the expense of treating cancers which offer little threat to health. He aims to detect only clinically relevant, aggressive prostate cancer while minimizing the diagnosis of clinically unimportant, low-risk cancers that would not progress even if left undetected and untreated.
While You’re Up, Get Me A Gall Bladder!
According to the publication Science Museums, there are currently 7 organs being grown in labs with a good degree of success:
Eyes: skin cells from individuals with rare genetic diseases are being used to grow eyecups.
Hearts: pluripotent stem cells are being used to form tissue resembling that of the human heart. In one instance, the tissue started beating after receiving an electric shock.
Skin: doctors in the U.S. have developed a new way to treat severe burns. By using a thin layer of stem cells taken from the actual patient and spraying them on the wound, the skin is allowed to heal evenly and completely. These skin cells are duplicated in the lab before being sprayed onto the patient, alleviating the need for painful skin grafts that are prone to develop serious infections.
Bone: stem cells taken from bone marrow are being suspended in a collagen gel and then exposed to nanovibrations. This creates a putty-like substance used to graft bones back together. This putty is typically softer than our bones but it has been used successfully to heal large bones, making them harder and stronger than before they broke.
Muscles: bundles of muscles that twitch and respond to electrical stimuli are being grown in labs. These muscles are grown from pluripotent stem cells taken from biopsies. Lab-grown muscles can be used in the development of new drugs needed to treat muscle conditions and to test the efficiency of treatments prior to drug use in humans.
Brains: scientists are using stem cells from children’s milk teeth and reprogramming them into neurons. These organoids closely resemble the early embryonic stages in the brain. The information gathered from this study helps scientists study the genetic mutations that take place in the brain.
Liver: using stem cells, scientists have grown liver cells that when transplanted into mice have actually formed their own blood supply and matured into adult liver cells. When tested, these livers showed normal liver functions. The objective is to eventually transplant fully-functioning lab-grown livers into humans.
Penises: Boston Scientific boasts that half-a-million patients have been treated with one of their zippy penile implants. The 3-piece Inflatable Implant features fluid-filled cylinders which expand in girth and length using a pump in the scrotum. The implant has antibiotics embedded in the surface to help prevent infection.
The 2-piece Inflatable offers simple inflation resulting in a rigid erection, an option for men with abdominal scarring which may prevent reservoir placement. The Malleable Penile Implant is a bendable cylinder easy to position and conceal even for men with limited dexterity.
All of these penis options are available at your nearest penile paraphernalia installation center or at our lively chain of Phalli ‘R’ Us stores. Look for us at the sign of the Flying Red Horse.
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That’s all, folks….
