New Hope for Organ Transplantation: Life Without Anti-Rejection Drugs
Rob Waddell dreaded getting a kidney transplant. He suffers from a genetic condition called polycystic kidney disease that causes the uncontrolled growth of cysts that gradually choke off kidney function. The inherited defect has haunted his family for generations, killing his great grandmother, grandmother, and numerous cousins, aunts and uncles.
But he saw how difficult it was for his mother and sister, who also suffer from this condition, to live with the side effects of the drugs they needed to take to prevent organ rejection, which can cause diabetes, high blood pressure and cancer, and even kidney failure because of their toxicity. Many of his relatives followed the same course, says Waddell: "They were all on dialysis, then a transplant and ended up usually dying from cancers caused by the medications."
When the Louisville native and father of four hit 40, his kidneys barely functioned and the only alternative was either a transplant or the slow death of dialysis. But in 2009, when Waddell heard about an experimental procedure that could eliminate the need for taking antirejection drugs, he jumped at the chance to be their first patient. Devised by scientists at the University of Louisville and Northwestern University, the innovative approach entails mixing stem cells from the live kidney donor with that of the recipient to create a hybrid immune system, known as a chimera, that would trick the immune system and prevent it from attacking the implanted kidney.
The procedure itself was done at Northwestern Memorial Hospital in Chicago, using a live kidney donated by a neighbor of Waddell's, who camped out in Chicago during his recovery. Prior to surgery, Waddell underwent a conditioning treatment that consisted of low dose radiation and chemotherapy to weaken his own immune system and make room for the infusion of stem cells.
"The low intensity chemo and radiation conditioning regimen create just enough space for the donor stem cells to gain a foothold in the bone marrow and the donor's immune system takes over," says Dr. Joseph Levanthal, the transplant surgeon who performed the operation and director of kidney and pancreas transplantation at Northwestern University Feinberg School of Medicine. "That way the recipient develops an immune system that doesn't see the donor organ as foreign."
"As a surgeon, I saw what my patients had to go through—taking 25 pills a day, dying at an early age from heart disease, or having a 35% chance of dying every year on dialysis."
A week later, Waddell had the kidney transplant. The following day, he was infused with a complex cellular cocktail that included blood-forming stem cells derived from his donor's bone marrow mixed what are called tolerance inducing facilitator cells (FCs); these cells help the foreign stem cells get established in the recipient's bone marrow.
Over the course of the following year, he was slowly weaned off of antirejection medications—a precaution in case the procedure didn't work—and remarkably, hasn't needed them since. "I felt better than I had in decades because my kidneys [had been] degrading," recalls Waddell, now 54 and a CPA for a global beverage company. And what's even better is that this new approach offers hope for one of his sons who has also inherited the disorder.
Kidney transplants are the most frequent organ transplants in the world and more than 23,000 of these procedures were done in the United States in 2019, according to the United Network for Organ Sharing. Of this, about 7,000 operations are done annually using live organ donors; the remainder use organs from people who are deceased. Right now, this revolutionary new approach—as well as a similar strategy formulated by Stanford University scientists--is in the final phase of clinical trials. Ultimately, this research may pave the way towards realizing the holy grail of organ transplantation: preventing organ rejection by creating a tolerant state in which the recipient's immune system is compatible with the donor, which would eliminate the need for a lifetime of medications.
"As a surgeon, I saw what my patients had to go through—taking 25 pills a day, dying at an early age from heart disease, or having a 35% chance of dying every year on dialysis," says Dr. Suzanne Ildstad, a transplant surgeon and director of the Institute for Cellular Therapeutics at the University of Louisville, whose discovery of facilitator cells were the basis for this therapeutic platform. Ildstad, who has spent more than two decades searching for a better way, says, "This is something I have worked for my entire life."
The Louisville group uses a combination of chemo and radiation to replace the recipient's immune and blood forming cells with that of the donor. In contrast, the Stanford protocol involves harvesting the donor's blood stem cells and T-cells, which are the foot soldiers of the immune system that fight off infections and would normally orchestrate the rejection of the transplanted organ. Their transplant recipients undergo a milder form of "conditioning" that only radiates discrete parts of the body and selectively targets the recipient's T-cells, creating room for both sets of T-cells, a strategy these researchers believe has a better safety profile and less of a chance of rejection.
"We try to achieve immune tolerance by a true chimerism," says Dr. Samuel Strober, a professor of medicine for immunology and rheumatology at Stanford University and a leader of this research team. "The recipients immune system cells are maintained but mixed in the blood with that of the donor."
Studies suggest both approaches work. In a 2018 clinical trial conducted by Talaris Therapeutics, a Louisville-based biotech founded by Ildstad, 26 of 37 (70%) of the live donor kidney transplant recipients no longer need immunosuppressants. Last fall, Talaris began the final phase of clinical tests that will eventually encompass more than 120 such patients.
The Stanford group's cell-based immunotherapy, which is called MDR-101 and is sponsored by the South San Francisco biotech, Medeor Therapeutics, has had similar results in patients who received organs from live donors who were either well matched, such as one from siblings, meaning they were immunologically identical, or partially matched; Talaris uses unrelated donors where there is only a partial match.
In their 2020 clinical trial of 51 patients, 29 were fully matched and 22 were a partial match; 22 of the fully matched recipients didn't need antirejection drugs and ten of the partial matches were able to stop taking some of these medications without rejection. "With our fully matched, roughly 80% have been completely off drugs up to 14 years later," says Strober, "and reducing the number of drugs from three to one [in the partial matches] means you have far fewer side effects. The goal is to get them off of all drugs."
But these protocols are limited to a small number of patients—living donor kidney recipients. As a consequence, both teams are experimenting with ways to broaden their approach so they can use cadaver organs from deceased donors, with human tests planned in the coming year. Here's how that would work: after the other organs are removed from a deceased donor, stem cells are harvested from the donor's vertebrae in the spinal column and then frozen for storage.
"We do the transplant and give the patient a chance to recover and maintain them on drugs," says Ildstad. "Then we do the tolerance conditioning at a later stage."
If this strategy is successful, it would be a genuine game changer, and open the door to using these protocols for transplanting other cadaver organs, including the heart, lungs and liver. While the overall procedure is complex and costly, in the long run it's less expensive than repeated transplant surgeries, the cost of medications and hospitalizations for complications caused by the drugs, or thrice weekly dialysis treatments, says Ildstad.
And she adds, you can't put a price tag on the vast improvement in quality of life.
A Mother-and-Daughter Team Have Developed What May Be the World’s First Alzheimer’s Vaccine
Alzheimer's is a terrible disease that robs a person of their personality and memory before eventually leading to death. It's the sixth-largest killer in the U.S. and, currently, there are 5.8 million Americans living with the disease.
Wang's vaccine is a significant improvement over previous attempts because it can attack the Alzheimer's protein without creating any adverse side effects.
It devastates people and families and it's estimated that Alzheimer's and other forms of dementia will cost the U.S. $290 billion dollars this year alone. It's estimated that it will become a trillion-dollar-a-year disease by 2050.
There have been over 200 unsuccessful attempts to find a cure for the disease and the clinical trial termination rate is 98 percent.
Alzheimer's is caused by plaque deposits that develop in brain tissue that become toxic to brain cells. One of the major hurdles to finding a cure for the disease is that it's impossible to clear out the deposits from the tissue. So scientists have turned their attention to early detection and prevention.
One very encouraging development has come out of the work done by Dr. Chang Yi Wang, PhD. Wang is a prolific bio-inventor; one of her biggest successes is developing a foot-and-mouth vaccine for pigs that has been administered more than three billion times.
Mei Mei Hu
Brainstorm Health / Flickr.
In January, United Neuroscience, a biotech company founded by Yi, her daughter Mei Mei Hu, and son-in-law, Louis Reese, announced the first results from a phase IIa clinical trial on UB-311, an Alzheimer's vaccine.
The vaccine has synthetic versions of amino acid chains that trigger antibodies to attack Alzheimer's protein the blood. Wang's vaccine is a significant improvement over previous attempts because it can attack the Alzheimer's protein without creating any adverse side effects.
"We were able to generate some antibodies in all patients, which is unusual for vaccines," Yi told Wired. "We're talking about almost a 100 percent response rate. So far, we have seen an improvement in three out of three measurements of cognitive performance for patients with mild Alzheimer's disease."
The researchers also claim it can delay the onset of the disease by five years. While this would be a godsend for people with the disease and their families, according to Elle, it could also save Medicare and Medicaid more than $220 billion.
"You'd want to see larger numbers, but this looks like a beneficial treatment," James Brown, director of the Aston University Research Centre for Healthy Ageing, told Wired. "This looks like a silver bullet that can arrest or improve symptoms and, if it passes the next phase, it could be the best chance we've got."
"A word of caution is that it's a small study," says Drew Holzapfel, acting president of the nonprofit UsAgainstAlzheimer's, said according to Elle. "But the initial data is compelling."
The company is now working on its next clinical trial of the vaccine and while hopes are high, so is the pressure. The company has already invested $100 million developing its vaccine platform. According to Reese, the company's ultimate goal is to create a host of vaccines that will be administered to protect people from chronic illness.
"We have a 50-year vision -- to immuno-sculpt people against chronic illness and chronic aging with vaccines as prolific as vaccines for infectious diseases," he told Elle.
[Editor's Note: This article was originally published by Upworthy here and has been republished with permission.]
Turning Algae Into Environmentally Friendly Fuel Just Got Faster and Smarter
Was your favorite beach closed this summer? Algae blooms are becoming increasingly the reason to blame and, as the climate heats up, scientists say we can expect more of the warm water-loving blue-green algae to grow.
"We have removed a significant development barrier to make algal biofuel production more efficient and smarter."
Oddly enough, the pesky growth could help fuel our carbon-friendly options.
This year, the University of Utah scientists discovered a faster way to turn algae into fuel. Algae is filled with lipids that we can feed our energy-hungry diesel engines. The problem is extracting the lipids, which usually requires more energy to transform than the actual energy we'd get – not achieving what scientists call "energy parity."
But now, the University of Utah team has discovered a new mix that is more efficient and much faster. We can now extract more power from algae with less waste materials after the fact. Paper co-author Dr. Leonard Pease says, "We have removed a significant development barrier to make algal biofuel production more efficient and smarter. Our method puts us much closer to creating biofuels energy parity than we were before."
Next Up
Algae has a lot going for it as an alternative fuel source. It grows fast and easily, absorbs carbon dioxide, does not compete with food crops for land, and could produce up to 60 times more oil than standard land-based energy crops, according to the U.S. Department of Energy. Yet the costs of algal biofuel production are still expensive for now.
According to Science Daily, only about five percent of total primary energy use in the United States came from algae and other biomass forms. By making the process more efficient, America and other nations could potentially begin relying on more plentiful resources – which, ironically, are more common now because of climate change.
Algae fuel efficiency is already a proven concept. A decade ago, Continental Airlines completed a 90-minute Boeing 737-800 flight with one engine split between biofuel and aircraft fuel. The biofuel was straight from algae. (Other flights were done based on nut fuel and other alternative sources.) The commercial airplane required no modification to the engine and the biofuel itself exceeded the standards of traditional jet fuel.
The problem, as noted at the time, is that biofuels derived from algae had yet to be proven as "commercially competitive."
The University of Utah's discovery could mean cheaper processing. At this point, it is less about if it works and more about if it is a practical alternative.
However, it's unclear how long it will take for algae to become more mainstream, if ever.
Open Questions
Higher efficiency and simpler transformations could mean lower prices and more business access. However, it's unclear how long it will take for algae to become more mainstream, if ever. The algae biofuel worked great for a relatively sophisticated Boeing 737 engine, but your family car, the cross-country delivery trucks and other less powerful machines may need to be modified – and that means the industry-at-large would have to revise their products in order to support the change.
Future-focused groups are already looking at how algae can fuel our space programs, especially if it is more renewable, safe and, potentially, cheaper than our traditional fuel choices. But first, it is worth waiting and seeing if corporations and, later, citizens are willing to take the plunge.