The World’s Most Famous Billionaires Are Joining Forces to Fight Alzheimer’s
Phil Gutis, an Alzheimer's patient who participated in a failed clinical trial, poses with his dog Abe.
Phil Gutis never had a stellar memory, but when he reached his early 50s, it became a problem he could no longer ignore. He had trouble calculating how much to tip after a meal, finding things he had just put on his desk, and understanding simple driving directions.
From 1998-2017, industry sources reported 146 failed attempts at developing Alzheimer's drugs.
So three years ago, at age 54, he answered an ad for a drug trial seeking people experiencing memory issues. He scored so low in the memory testing he was told something was wrong. M.R.I.s and PET scans confirmed that he had early-onset Alzheimer's disease.
Gutis, who is a former New York Times reporter and American Civil Liberties Union spokesman, felt fortunate to get into an advanced clinical trial of a new treatment for Alzheimer's disease. The drug, called aducanumab, had shown promising results in earlier studies.
Four years of data had found that the drug effectively reduced the burden of protein fragments called beta-amyloids, which destroy connections between nerve cells. Amyloid plaques are found in the brains of patients with Alzheimer's disease and are associated with impairments in thinking and memory.
Gutis eagerly participated in the clinical trial and received 35 monthly infusions. "For the first 20 infusions, I did not know whether I was receiving the drug or the placebo," he says. "During the last 15 months, I received aducanumab. But it really didn't matter if I was receiving the drug or the placebo because on March 21, the trial was stopped because [the drug company] Biogen found that the treatments were ineffective."
The news was devastating to the trial participants, but also to the Alzheimer's research community. Earlier this year, another pharmaceutical company, Roche, announced it was discontinuing two of its Alzheimer's clinical trials. From 1998-2017, industry sources reported 146 failed attempts at developing Alzheimer's drugs. There are five prescription drugs approved to treat its symptoms, but a cure remains elusive. The latest failures have left researchers scratching their heads about how to approach attacking the disease.
The failure of aducanumab was also another setback for the estimated 5.8 million people who have Alzheimer's in the United States. Of these, around 5.6 million are older than 65 and 200,000 suffer from the younger-onset form, including Gutis.
Gutis is understandably distraught about the cancellation of the trial. "I really had hopes it would work. So did all the patients."
While drug companies have failed so far, another group is stepping up to expedite the development of a cure: venture philanthropists.
For now, he is exercising every day to keep his blood flowing, which is supposed to delay the progression of the disease, and trying to eat a low-fat diet. "But I know that none of it will make a difference. Alzheimer's is a progressive disease. There are no treatments to delay it, let alone cure it."
But while drug companies have failed so far, another group is stepping up to expedite the development of a cure: venture philanthropists. These are successful titans of industry and dedicated foundations who are donating large sums of money to fill a much-needed void – funding research to look for new biomarkers.
Biomarkers are neurochemical indicators that can be used to detect the presence of a disease and objectively measure its progression. There are currently no validated biomarkers for Alzheimer's, but researchers are actively studying promising candidates. The hope is that they will find a reliable way to identify the disease even before the symptoms of mental decline show up, so that treatments can be directed at a very early stage.
Howard Fillit, Founding Executive Director and Chief Science Officer of the Alzheimer's Drug Discovery Foundation, says, "We need novel biomarkers to diagnose Alzheimer's disease and related dementias. But pharmaceutical companies don't put money into biomarkers research."
One of the venture philanthropists who has recently stepped up to the task is Bill Gates. In January 2018, he announced his father had Alzheimer's disease in an interview on the Today Show with Maria Shriver, whose father Sargent Shriver, died of Alzheimer's disease in 2011. Gates told Ms. Shriver that he had invested $100 million into Alzheimer's research, with $50 million of his donation going to Dementia Discovery Fund, which looks for new cures and treatments.
That August, Gates joined other investors in a new fund called Diagnostics Accelerator. The project aims to supports researchers looking to speed up new ideas for earlier and better diagnosis of the disease.
Gates and other donors committed more than $35 million to help launch it, and this April, Jeff and Mackenzie Bezos joined the coalition, bringing the current program funding to nearly $50 million.
"It makes sense that a challenge this significant would draw the attention of some of the world's leading thinkers."
None of these funders stand to make a profit on their donation, unlike traditional research investments by drug companies. The standard alternatives to such funding have upsides -- and downsides.
As Bill Gates wrote on his blog, "Investments from governments or charitable organizations are fantastic at generating new ideas and cutting-edge research -- but they're not always great at creating usable products, since no one stands to make a profit at the end of the day.
"Venture capital, on the other end of the spectrum, is more likely to develop a test that will reach patients, but its financial model favors projects that will earn big returns for investors. Venture philanthropy splits the difference. It incentivizes a bold, risk-taking approach to research with an end goal of a real product for real patients. If any of the projects backed by Diagnostics Accelerator succeed, our share of the financial windfall goes right back into the fund."
Gutis said he is thankful for any attention given to finding a cure for Alzheimer's.
"Most doctors and scientists will tell you that we're still in the dark ages when it comes to fully understanding how the brain works, let alone figuring out the cause or treatment for Alzheimer's.
"It makes sense that a challenge this significant would draw the attention of some of the world's leading thinkers. I only hope they can be more successful with their entrepreneurial approach to finding a cure than the drug companies have been with their more traditional paths."
Urinary tract infections account for more than 8 million trips to the doctor each year.
Few things are more painful than a urinary tract infection (UTI). Common in men and women, these infections account for more than 8 million trips to the doctor each year and can cause an array of uncomfortable symptoms, from a burning feeling during urination to fever, vomiting, and chills. For an unlucky few, UTIs can be chronic—meaning that, despite treatment, they just keep coming back.
But new research, presented at the European Association of Urology (EAU) Congress in Paris this week, brings some hope to people who suffer from UTIs.
Clinicians from the Royal Berkshire Hospital presented the results of a long-term, nine-year clinical trial where 89 men and women who suffered from recurrent UTIs were given an oral vaccine called MV140, designed to prevent the infections. Every day for three months, the participants were given two sprays of the vaccine (flavored to taste like pineapple) and then followed over the course of nine years. Clinicians analyzed medical records and asked the study participants about symptoms to check whether any experienced UTIs or had any adverse reactions from taking the vaccine.
The results showed that across nine years, 48 of the participants (about 54%) remained completely infection-free. On average, the study participants remained infection free for 54.7 months—four and a half years.
“While we need to be pragmatic, this vaccine is a potential breakthrough in preventing UTIs and could offer a safe and effective alternative to conventional treatments,” said Gernot Bonita, Professor of Urology at the Alta Bro Medical Centre for Urology in Switzerland, who is also the EAU Chairman of Guidelines on Urological Infections.
The news comes as a relief not only for people who suffer chronic UTIs, but also to doctors who have seen an uptick in antibiotic-resistant UTIs in the past several years. Because UTIs usually require antibiotics, patients run the risk of developing a resistance to the antibiotics, making infections more difficult to treat. A preventative vaccine could mean less infections, less antibiotics, and less drug resistance overall.
“Many of our participants told us that having the vaccine restored their quality of life,” said Dr. Bob Yang, Consultant Urologist at the Royal Berkshire NHS Foundation Trust, who helped lead the research. “While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game-changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.”
MILESTONE: Doctors have transplanted a pig organ into a human for the first time in history
A surgeon at Massachusetts General Hospital prepares a pig organ for transplant.
Surgeons at Massachusetts General Hospital made history last week when they successfully transplanted a pig kidney into a human patient for the first time ever.
The recipient was a 62-year-old man named Richard Slayman who had been living with end-stage kidney disease caused by diabetes. While Slayman had received a kidney transplant in 2018 from a human donor, his diabetes ultimately caused the kidney to fail less than five years after the transplant. Slayman had undergone dialysis ever since—a procedure that uses an artificial kidney to remove waste products from a person’s blood when the kidneys are unable to—but the dialysis frequently caused blood clots and other complications that landed him in the hospital multiple times.
As a last resort, Slayman’s kidney specialist suggested a transplant using a pig kidney provided by eGenesis, a pharmaceutical company based in Cambridge, Mass. The highly experimental surgery was made possible with the Food and Drug Administration’s “compassionate use” initiative, which allows patients with life-threatening medical conditions access to experimental treatments.
The new frontier of organ donation
Like Slayman, more than 100,000 people are currently on the national organ transplant waiting list, and roughly 17 people die every day waiting for an available organ. To make up for the shortage of human organs, scientists have been experimenting for the past several decades with using organs from animals such as pigs—a new field of medicine known as xenotransplantation. But putting an animal organ into a human body is much more complicated than it might appear, experts say.
“The human immune system reacts incredibly violently to a pig organ, much more so than a human organ,” said Dr. Joren Madsen, director of the Mass General Transplant Center. Even with immunosuppressant drugs that suppress the body’s ability to reject the transplant organ, Madsen said, a human body would reject an animal organ “within minutes.”
So scientists have had to use gene-editing technology to change the animal organs so that they would work inside a human body. The pig kidney in Slayman’s surgery, for instance, had been genetically altered using CRISPR-Cas9 technology to remove harmful pig genes and add human ones. The kidney was also edited to remove pig viruses that could potentially infect a human after transplant.
With CRISPR technology, scientists have been able to prove that interspecies organ transplants are not only possible, but may be able to successfully work long term, too. In the past several years, scientists were able to transplant a pig kidney into a monkey and have the monkey survive for more than two years. More recently, doctors have transplanted pig hearts into human beings—though each recipient of a pig heart only managed to live a couple of months after the transplant. In one of the patients, researchers noted evidence of a pig virus in the man’s heart that had not been identified before the surgery and could be a possible explanation for his heart failure.
So far, so good
Slayman and his medical team ultimately decided to pursue the surgery—and the risk paid off. When the pig organ started producing urine at the end of the four-hour surgery, the entire operating room erupted in applause.
Slayman is currently receiving an infusion of immunosuppressant drugs to prevent the kidney from being rejected, while his doctors monitor the kidney’s function with frequent ultrasounds. Slayman is reported to be “recovering well” at Massachusetts General Hospital and is expected to be discharged within the next several days.