The World’s Most Famous Billionaires Are Joining Forces to Fight Alzheimer’s
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."
A new type of cancer therapy is shrinking deadly brain tumors with just one treatment
Few cancers are deadlier than glioblastomas—aggressive and lethal tumors that originate in the brain or spinal cord. Five years after diagnosis, less than five percent of glioblastoma patients are still alive—and more often, glioblastoma patients live just 14 months on average after receiving a diagnosis.
But an ongoing clinical trial at Mass General Cancer Center is giving new hope to glioblastoma patients and their families. The trial, called INCIPIENT, is meant to evaluate the effects of a special type of immune cell, called CAR-T cells, on patients with recurrent glioblastoma.
How CAR-T cell therapy works
CAR-T cell therapy is a type of cancer treatment called immunotherapy, where doctors modify a patient’s own immune system specifically to find and destroy cancer cells. In CAR-T cell therapy, doctors extract the patient’s T-cells, which are immune system cells that help fight off disease—particularly cancer. These T-cells are harvested from the patient and then genetically modified in a lab to produce proteins on their surface called chimeric antigen receptors (thus becoming CAR-T cells), which makes them able to bind to a specific protein on the patient’s cancer cells. Once modified, these CAR-T cells are grown in the lab for several weeks so that they can multiply into an army of millions. When enough cells have been grown, these super-charged T-cells are infused back into the patient where they can then seek out cancer cells, bind to them, and destroy them. CAR-T cell therapies have been approved by the US Food and Drug Administration (FDA) to treat certain types of lymphomas and leukemias, as well as multiple myeloma, but haven’t been approved to treat glioblastomas—yet.
CAR-T cell therapies don’t always work against solid tumors, such as glioblastomas. Because solid tumors contain different kinds of cancer cells, some cells can evade the immune system’s detection even after CAR-T cell therapy, according to a press release from Massachusetts General Hospital. For the INCIPIENT trial, researchers modified the CAR-T cells even further in hopes of making them more effective against solid tumors. These second-generation CAR-T cells (called CARv3-TEAM-E T cells) contain special antibodies that attack EFGR, a protein expressed in the majority of glioblastoma tumors. Unlike other CAR-T cell therapies, these particular CAR-T cells were designed to be directly injected into the patient’s brain.
The INCIPIENT trial results
The INCIPIENT trial involved three patients who were enrolled in the study between March and July 2023. All three patients—a 72-year-old man, a 74-year-old man, and a 57-year-old woman—were treated with chemo and radiation and enrolled in the trial with CAR-T cells after their glioblastoma tumors came back.
The results, which were published earlier this year in the New England Journal of Medicine (NEJM), were called “rapid” and “dramatic” by doctors involved in the trial. After just a single infusion of the CAR-T cells, each patient experienced a significant reduction in their tumor sizes. Just two days after receiving the infusion, the glioblastoma tumor of the 72-year-old man decreased by nearly twenty percent. Just two months later the tumor had shrunk by an astonishing 60 percent, and the change was maintained for more than six months. The most dramatic result was in the 57-year-old female patient, whose tumor shrank nearly completely after just one infusion of the CAR-T cells.
The results of the INCIPIENT trial were unexpected and astonishing—but unfortunately, they were also temporary. For all three patients, the tumors eventually began to grow back regardless of the CAR-T cell infusions. According to the press release from MGH, the medical team is now considering treating each patient with multiple infusions or prefacing each treatment with chemotherapy to prolong the response.
While there is still “more to do,” says co-author of the study neuro-oncologist Dr. Elizabeth Gerstner, the results are still promising. If nothing else, these second-generation CAR-T cell infusions may someday be able to give patients more time than traditional treatments would allow.
“These results are exciting but they are also just the beginning,” says Dr. Marcela Maus, a doctor and professor of medicine at Mass General who was involved in the clinical trial. “They tell us that we are on the right track in pursuing a therapy that has the potential to change the outlook for this intractable disease.”
Since the early 2000s, AI systems have eliminated more than 1.7 million jobs, and that number will only increase as AI improves. Some research estimates that by 2025, AI will eliminate more than 85 million jobs.
But for all the talk about job security, AI is also proving to be a powerful tool in healthcare—specifically, cancer detection. One recently published study has shown that, remarkably, artificial intelligence was able to detect 20 percent more cancers in imaging scans than radiologists alone.
Published in The Lancet Oncology, the study analyzed the scans of 80,000 Swedish women with a moderate hereditary risk of breast cancer who had undergone a mammogram between April 2021 and July 2022. Half of these scans were read by AI and then a radiologist to double-check the findings. The second group of scans was read by two researchers without the help of AI. (Currently, the standard of care across Europe is to have two radiologists analyze a scan before diagnosing a patient with breast cancer.)
The study showed that the AI group detected cancer in 6 out of every 1,000 scans, while the radiologists detected cancer in 5 per 1,000 scans. In other words, AI found 20 percent more cancers than the highly-trained radiologists.
Scientists have been using MRI images (like the ones pictured here) to train artificial intelligence to detect cancers earlier and with more accuracy. Here, MIT's AI system, MIRAI, looks for patterns in a patient's mammograms to detect breast cancer earlier than ever before. news.mit.edu
But even though the AI was better able to pinpoint cancer on an image, it doesn’t mean radiologists will soon be out of a job. Dr. Laura Heacock, a breast radiologist at NYU, said in an interview with CNN that radiologists do much more than simply screening mammograms, and that even well-trained technology can make errors. “These tools work best when paired with highly-trained radiologists who make the final call on your mammogram. Think of it as a tool like a stethoscope for a cardiologist.”
AI is still an emerging technology, but more and more doctors are using them to detect different cancers. For example, researchers at MIT have developed a program called MIRAI, which looks at patterns in patient mammograms across a series of scans and uses an algorithm to model a patient's risk of developing breast cancer over time. The program was "trained" with more than 200,000 breast imaging scans from Massachusetts General Hospital and has been tested on over 100,000 women in different hospitals across the world. According to MIT, MIRAI "has been shown to be more accurate in predicting the risk for developing breast cancer in the short term (over a 3-year period) compared to traditional tools." It has also been able to detect breast cancer up to five years before a patient receives a diagnosis.
The challenges for cancer-detecting AI tools now is not just accuracy. AI tools are also being challenged to perform consistently well across different ages, races, and breast density profiles, particularly given the increased risks that different women face. For example, Black women are 42 percent more likely than white women to die from breast cancer, despite having nearly the same rates of breast cancer as white women. Recently, an FDA-approved AI device for screening breast cancer has come under fire for wrongly detecting cancer in Black patients significantly more often than white patients.
As AI technology improves, radiologists will be able to accurately scan a more diverse set of patients at a larger volume than ever before, potentially saving more lives than ever.