As Siobhan Ellison daily pursues answers to the catastrophe which is Amyotrophic Lateral Sclerosis, we are able to observe the beehives of research activity in multiple spheres throughout the world normally unrecognized by the general public. These researchers are like the Germanic tribes assaulting Rome, so numerous and so avid that sooner or later the gates must fall. No matter how perplexing the quandary, the battle of Adrianople will eventually go to the aggressors….you just have to stay alive long enough for the walls to crumble. As the advocates of Patience never fail to remind us, Rome wasn’t conquered in a day.
Wonder Wart Hog To The Rescue!
After years of dedicated research, surgeons could be transplanting….wait for it….pig hearts into humans by 2021, according to a recent analysis published in Circulation. Due to “special circumstances,” Gilbert Shelton and Bill Killeen are foremost in line for the new thumpers.
Cardiac xenotransplantation, or the act of transplanting a heart from one species into the body of another, has been a longtime goal of researchers all over the world. The team behind this new analysis, based out of Massachusetts General Hospital, noted that several recent breakthroughs could help make cardiac xenotransplantation between pigs and humans a reality in the very near future. For example, genetic engineering has helped stop the immune systems of primates from marking pig hearts as “foreign” and attacking them. Pigs have also been engineered that can can produce a human protein for limiting blood clotting, solving another significant issue often connected with cardiac xeno. In addition, researchers have developed new drugs that suppress the immune systems of transplant recipients when the organ comes from a different species.
One of the biggest questions surrounding cardiac xeno with pigs and humans, of course, is patient safety. Could such a process lead to humans being struck with infectious diseases, for instance? Or might people begin to get more sloppy, increasingly disinclined to neaten up their domiciles leading to an increase in human “pigsties?” Other questions arise. Will corncobs begin to appear in the produce isles of Publix markets? Will soya bean meal sales soar? Will Nancy Kay finally be right in her 1967 slandering of Bill Killeen as a capitalist pig? (Okay, that’s a slight exaggeration.)
“All of that looks quite unlikely,” says lead author of the Circulation article, Richard N. Pierson III, MD, division of cardiac surgery at MGH and a professor at Harvard Medical School. “This is the culmination of a lot of research and hard work by our group and others over the last 35 years. It looks as though pig-to-human heart transplantation is feasible. We expect to be in business by the end of 2021.”
Percival Q. Porcine, a spokesman for the Associated Swine of Iowa, was aghast at the prospect. "I beg your pardon!" he sputtered, recoiling in terror.
We know there will be a lot of doubters out there, but we implore you not to be pig-headed about it. Oink! Oink!
And Don’t Forget It!
After hippity-hopping down the bunny trail for ten years, Cambridge-based Biogen has almost reached the burrow of Fruition. Its Alzheimer’s drug, aducanumab, is perched outside the Food and Drug Administration’s door, waiting for an invite inside. The FDA has accepted Biogen’s application, complete with phase one to three clinical trials, for the treatment’s approval. The agency will decide whether the new treatment is approved for use in clinics by March 7, 2021.
“I think there’s a reasonable chance that aducanumab, if approved, will be the first disease-modifying agent for Alzheimer’s,” says Dr. Dennis Selkoe, professor of neurologic diseases at Brigham and Women’s Hospital and Harvard Medical School. “It will be a huge milestone, and patients of mine, as well as others, can access the drug.” Selkoe did not work with Biogen, but some of his patients were involved in the drug’s clinical trials.
“Aducanumab is an antibody,” Selkoe continues. "It binds to the amyloid beta protein, especially aggregate forms of the amyloid beta protein that we consider to be the principal bad guy in Alzheimer’s disease. The disease begins in most cases with the buildup of this small protein and the formation of amyloid beta plaques. There’s a lot of evidence that people with too much of this protein develop Alzheimer’s. Aducanumab binds to amyloid beta protein. It mobilizes the body’s immune system against the amyloid beta plaques and seems to clear the plaques, themselves.”
The next step in Alzheimer’s is resolving the buildup of toxic tangles of a protein called tau, as well as the accumulation of tau in an abnormal form called phospho-tau. Participants in Biogen’s clinical trials saw their amyloid plaque burden recede and the tau burden also went down. Aducanumab is not yet stopping the decline in its tracks but it is slowing down significantly. "Right now, that’s all we were hoping for," said Selkoe. "You need to walk before you run and we’re rolling like the Roadrunner.”
Good News For Geezers
“Here it is, the elixir of life!” says Joan Mannick, jokingly, as she reveals a shiny, salmon-pink pill called RTB101, a new marvel developed by Mannick’s Boston-based biotech company that could change the future of aging forever (and are all these bio companies located in the Boston-Cambridge wondersphere?).
Similar drugs have expanded the lives of countless worms, fruit flies and mice by slowing down an ancient aging process. But unlike the other promising substances which have come and gone, this one has been shown to work in another notable species—humans.
In studies of more than 900 people by Mannick and her team, RTB101 bolstered aging immune systems, cut risk for respiratory diseases and may have lowered the risk for urinary tract infections. A version of the drug could win FDA approval as early as 2021 for a single age-related health threat: the winter colds, flu, pneumonia and other respiratory tract infections that send over one million adults to the hospital every year and kill more than 75,000. Studies of the drug as a preventative for Parkinson’s disease are set for later this year with additional research looking into its effect in reducing heart failure being eyed for sometime in the future.
In the hot world of aging science, RTB101 is the new A-list celebrity, the biggest star in the current quest for a drug which extends the healthy lifespan, a search aided by the National Institute of Health’s little-known taxpayer-funded Interventions Testing Program. One of the best-kept secrets in aging research, the $4.7 million a year ITP has moved promising drugs ahead while debunking other big antiaging crazes.
“We’ve reached the perfect storm in aging science,” says physician Nir Barzilai, founding director for the Institute for Aging Research at Yeshiva University’s Albert Einstein College of Medicine in the Bronx, New York. “Everything is happening. We have the foundation from decades of animal studies. We’re ready to move on to people!”
“Whew, just in the nick of time!” says trial candidate Bill Killeen of Fairfield, Florida. “I was worried I might wear out while waiting for the bus. Joan, where are you? I’m ready for my pill now.”
MS Alleluia
Nearly 85% of those with Multiple Sclerosis have a relapsing-remitting course. They experience periods of new symptoms or relapses that develop over days or weeks and usually improve partially or entirely. These relapses are followed by quiet periods of disease remission that can last months or even years. At least 50% of those with relapsing-remitting MS eventually develop a steady progression of symptoms, with or without periods of remission, within 10 to 20 years of disease onset. This is known as secondary-progressive MS. Approximately 15% of people with MS experience a gradual onset and steady progression of signs and symptoms without any relapses, a subset known as primary-progressive.
Despite a raft of FDA-approved disease-modifying therapies, nothing has slowed the progression of the disease. Not until now. But a novel monoclonal antibody called ocrelizumab might soon ring the gong. This drug targets a type of immune cell called CD20-positive B cell that plays a key role in the disease. Given once every month by intravenous infusion, ocrelizumab is the first and only MS treatment to target these specialized cells and treat the primary-progressive population
Positive results from a Phase III study of the drug showed significantly slower disability progression over a median treatment duration of three years when compared to placebo; patients were 24% less likely to have disability progression for thee months. Separate analysis of the same study showed greater patient satisfaction after one year with the treatment. More than 120,000 people have been treated with ocrelizumab globally and data continue to show a consistent and favorable benefit/risk profile in clinical trials and real-world settings. The Cleveland Clinic has named ocrelizumab one of its Top Ten Medical Innovations for 2021.
Okay, so if you’re a male between the ages of 70 and 80, half of you are going to get that tap on the shoulder advising you that prostate cancer has crept into your innards. I was one of the tappees, so I have a special interest in the subject despite the fact my personal prostate is dead and buried.
Most men discover their prostate issue via the PSA test performed at virtually all annual physicals. If your PSA number is going up, especially past 4, you’ve likely got problems. But mine never went up at all. It took a digital exam and a biopsy to discover prostate cancer was knocking at the door. As soon as it started actually kicking, I had the varmint removed by Dr. Li-Ming Su and his magic Da Vinci robot at the University of Florida, and I have lived happily forever after. Hooray for me.
The rest of you will be happy to know there is a new crime-fighter in the neighborhood. PARP inhibitors are a group of pharmacological critters of the enzyme poly ADP-ribose polymerase. They are drugs developed for multiple indications, including the treatment of heritable cancers. The PARP inhibitors rucaparib and olaparib have been shown to delay the progression of prostate cancer in men with refractory cancer and have recently been approved for use by the FDA. Olaparib’s approval was based on results of a Phase III PROfound trial, which showed a statistically significant and clinically meaningful improvement in the primary endpoint of radiographic progression-free survival versus standard antiandrogen hormone therapies. Specifically, the drug reduced the risk of disease progression or death by a whopping 66%. The FDA approval for rucaparib was based on data from a multi-center, single-arm TRITON2 Phase II clinical trial. Rucaparib produced a 44% overall response rate and achieved a 55% PSA response---rates associated with better rPFS and overall survival.
You might want to advise your friendly, neighborhood urologist. Sometimes they don’t know these things. Oh, and don’t wait for the after-Christmas sale at Walgreen’s.
That’s all, folks….
bill.killeen094@gmail.com
LIFEGUARD ALERT!
Two days ago, I went in for my regular Cardiology update. All went reasonably well. My ejection fraction, which swamped out at a scary 30 in February, had bounced back to the low 40s. My total cholesterol, aided by Lipitor, was down from 184 to 136 and dancing around the building. Everything else was merry, with one exception: my pacemaker, which records any aberrant cardio behavior for posterity, had picked up a smidge of atrial fibrillation in the past three months. My doctor, Daniel Van Roy of CVI Gainesville, told me a person might go on indefinitely with this sort of thing and have no problems. He also related that 5-10% would have a stroke. No problem, though, Eliquis used twice daily will reduce those percentages to zero. I asked about the legion of side effects mentioned on the television ads. Van Roy said he never had a patient with any side effects and even his mother was on the stuff. Needless to say, I am now taking Eliquis.
Here's how this affects the rest of you. Dr. Van Roy reports the major reason for atrial fib is simply age. Sooner or later, most people will experience it. The problem being, they might never know it...like me. I had absolutely no physical indication there was a problem, only the pacemaker knew. And most people don't have pacemakers. So anyone out there with the slightest hint of fibrillation should consult his cardiologist immediately. The thought arises that some people should be put on the drug as a preventative but it's pretty expensive and your insurance company will not approve it unless you actually have had incidences of atrial fib. At any rate, the matter is worth discussing with your doctor. Or you could just get a pacemaker when the prices go down for the annual Washington's Birthday sales.
