2021 Disruptive Dozen
The three-day forum concluded with the introduction of the Disruptive Dozen—12 new technologies identified by senior leaders from Mass General Brigham as having the chance to significantly improve healthcare in the next two years.
#12 | New Gene and Cell Therapies to Fight a Formidable Brain Cancer
Glioblastoma is the most common type of brain cancer in adults, but tragically, most patients die within a year to 18 months of diagnosis. Now, teams of scientists are bringing the tools of gene and cell therapy to bear on this formidable cancer. Using a variety of approaches — from cancer-killing viruses to rewired immune cells to even cancer cells themselves — the researchers are working to develop a slate of innovative treatments with the power to eradicate glioblastoma tumors and give patients longer, cancer-free lives.
#11 | Antisense Oligonucleotides: A Novel Therapeutic Platform for Neurodegenerative Disease
Some gene therapies seek to repair or replace what’s been lost, like genes that are abnormally silent because of a genetic misspelling that terminates their usual function. But other genes can be broken in a different way that gives them new, often unexpected behaviors. To address these wayward genes, scientists have devised a class of innovative gene therapies called antisense oligonucleotides, or ASOs. They are designed with biochemical precision to shut down the activity of a target gene at its molecular roots and hold promise for neurodegenerative diseases.
#10 | Improving Gene Therapy through Designer Viruses
A virus found in nature has become a workhorse of gene therapy. Known as adeno-associated virus, or AAV, it is a popular choice among gene therapy developers because of its long track record of safety and robust gene delivery in preclinical studies. But it’s not a perfect solution. That’s why scientists are working to create designer AAVs in the laboratory that address some of the virus’ shortcomings. The work promises to expand the clinical impact of gene therapy by broadening the number of patients and diseases that can benefit.
#9 | Building the Next Wave of CAR-T-cell Therapies
CAR-T therapy is a groundbreaking form of gene and cell therapy in which a patient’s own immune cells are isolated, genetically rewired in the laboratory to endow them with certain therapeutic properties, and then infused back into the bloodstream. For difficult to treat blood cancers, CAR-T therapies have proven remarkably effective, with some patients living for years cancer-free. Researchers are now working to expand the reach of this transformative technology by simplifying cell production and manufacturing and applying the approach to other disease areas.
#8 | Replacing What’s Lost: Stem Cell Therapies for Diabetes
Type 1 diabetes affects over a million people in the U.S. Day in and day out, patients must keep track of the levels of sugar in their blood and inject themselves periodically with insulin, all because the cells in their own bodies that supply the hormone have been destroyed by the immune system. Now, scientists are working on a novel cell-based treatment for type 1 diabetes that involves replacing these lost insulin-producing cells with a special laboratory-grown variety.
#7 | From Blood Cells to Neurons: A Groundbreaking Cell Therapy for Parkinson’s Disease
Approximately 10 million people worldwide suffer from Parkinson’s disease, a chronic condition that stems from the progressive loss of dopamine-producing neurons in the brain, which help control movement. The precise causes remain unclear and likely involve a mix of genes and environmental factors. Unfortunately, there is no available drug that protects or stops the neurons from dying. But scientists and clinicians are developing a revolutionary approach to replace these lost neurons, harnessing stem cell-based methods to convert patients’ own blood cells into dopamine-producing neurons.
#6 | Eyes and Ears: Expanding Gene Therapy’s Reach
The eye is among the vanguards of gene therapy. One of the first gene therapies approved in the U.S. treats a rare genetic form of blindness with a one-time injection into the eye. Its success is paving the way for a spate of other eye gene therapies that are now under development. Scientists are also pursuing novel gene therapies for another critical sensory organ, the ear. With over 150 genes tied to hearing loss and deafness, there is a great need for treatments that can help protect and restore hearing.
#5 | A Faster Way to Mobilize Bone Marrow Stem Cells
Some life-saving therapies, including certain forms of gene therapy, depend on bone marrow stem cells. But these cells are not easily accessible and require daily injections over several days to coax the stems cells out of the bone marrow and into the blood stream. The protocol is long and can cause pain, nausea, and other complications. Scientists are developing a new approach that promises to streamline this process and help reduce the barriers that can hinder the delivery of some gene therapies.
#4 | Moving Beyond Viruses to Ferry Genes
The first gene therapies to reach the clinic use viruses, which have been molecularly honed and tailored to allow for the safe, effective delivery of human genes. While these viruses can transfer genes into cells — a requirement for gene therapy — they are not a perfect solution. Now, as scientists seek to build next-generation gene therapies, they are pursuing alternatives for gene delivery. These include highly sophisticated beads fashioned from nanoparticles, which help protect and direct gene therapies to their intended destination within the body.
#3 | All About that Base: The Rise of a New Class of Genome-Editing Tools
Genome editing technologies are having a significant impact across biomedicine, especially on the field of gene therapy. Despite their precision and ease of use, these tools cannot fix every genetic mutation, including those that can be fixed by changing a single genetic base — like a one-letter misspelling in a book. Now, thanks to a new class of genome-editing tools, known as base editors, it is feasible to correct some of these so-called point mutations. The first base-editing therapies are now under development for a range of human diseases.
#2 | A Genetic Fix for Two Common Blood Disorders
Hemoglobin is a critical protein that works inside blood cells to transport oxygen throughout the body. When genetic mutations result in the production of abnormal forms of hemoglobin or a reduced amount of this protein, they can cause devastating diseases, including sickle-cell disease and beta-thalassemia. These conditions are common and can only be cured by a bone marrow transplant, which is risky and often not feasible due to the lack of a suitable donor. Now, new genome editors — tools that make precise changes to a person’s DNA — are paving the way toward a different kind of cure.
#1 | A New Generation of Cholesterol-Lowering Therapies
High cholesterol can often lead to heart disease. That’s why it’s important to maintain healthy blood cholesterol levels through proper diet and exercise. Doctors can also prescribe a cholesterol-lowering drug, but not all patients benefit from them and some experience side effects. Scientists have been working to devise new treatments for high cholesterol and other harmful fats, called “lipids.” Over the last several years, they’ve discovered key genes involved in cholesterol and lipid metabolism. Now, a wave of groundbreaking, gene therapies that target these genes is on the horizon.
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