At this recent GoldLab Symposium presentation in Colorado, parent Matt Might shows how it’s done.
People credit rapid next-generation gene sequencing for the increased pace of medical discovery. But patients and their families—especially those with rare or undiagnosed conditions—are emerging as the true engines of precision medicine. Racing against the clock to save their children, parents are building databanks, connecting scientific dots and fueling therapeutic advances that could otherwise take a decade or more to happen.
A report this April rocked the scientific world: scientists in China reported editing the genomes of human embryos using CRISPR/Cas9 technology. It was a limited success: of 86 embryos injected with CRISPR/Cas9, only 71 survived and only 4 had their target gene successfully edited. The edits didn’t take in every cell, creating a mosaic pattern, and worse, unwanted DNA mutations were introduced.
“Their study should give pause to any practitioner who thinks the technology is ready for testing to eradicate disease genes during [in vitro fertilization],” George Q. Daley, MD, PhD, director of the Stem Cell Transplantation Program at Boston Children’s Hospital, told The New York Times. “This is an unsafe procedure and should not be practiced at this time, and perhaps never.”
As Daley detailed last week in his excellent presentation at Harvard Medical School’s Talks@12 series, the report reignited an ethical debate around tampering with life that’s hummed around genetic and stem cell research for decades. What the Chinese report adds is the theoretical capability of not just changing your genetic makeup, but changing the DNA you pass on to your children.
Second in a two-part series on metabolic liver disease. Read part 1.
According to the American Liver Foundation, about 1 in 10 Americans have some form of liver disease. One rare, under-recognized disorder, lysosomal acid lipase (LAL) deficiency, can fly under the radar until it becomes life-threatening, often requiring a liver transplant. LAL deficiency currently has no specific treatment, but that may change thanks to combined expertise in genetics, metabolism and hepatology.
“LAL deficiency is currently under-diagnosed,” Neilan says. “We think the disease is more common than doctors have thought and now, with a treatment in trial, it is of greater importance to identify those patients so they may have better outcomes.”
First in a two-part series on metabolic liver disease. Read part 2.
In the clinical world, Boston Children’s Hospital surgeon Khashayar Vakili, MD, specializes in liver, kidney and intestinal transplant surgeries, while in the lab he is doing work which, for some patients, could eliminate the need for a transplant surgeon altogether.
Nikkola Carmichael, MS, CGC, is a parent and a genetic counselor in the adult genetics clinic at Brigham and Women’s Hospital. Her research was conducted as part of her master’s degree in genetic counseling in conjunction with colleagues at Boston Children’s Hospital.
When a parent or provider first becomes concerned about a child’s development, a diagnostic odyssey begins. It may be brief or can stretch for years as a child undergoes multiple procedures and medical appointments in the search for a diagnosis.
This is a challenging time for families. While learning to address their child’s health needs and fearing for the future, parents may have difficulty accessing support services due to the lack of a diagnosis. Against this backdrop of emotional turmoil, parents strive to support their child through medical procedures that can be painful or frightening.
In the U.S. alone, an estimated 30 million Americans suffer from a rare disorder. Many of them never receive a diagnosis, and often find themselves on a lonely journey, going from doctor to doctor and test to test, sometimes for many years, with no explanation for their symptoms.
How many people fall in the “undiagnosed” category is unclear, but in its first six years, the NIH’s Undiagnosed Diseases Program has received more than 10,000 inquiries. Without a diagnosis, it’s often difficult to qualify for insurance coverage, receive coordinated care or even connect with a support group.
What if the work of solving these medical mysteries could be crowd-sourced? That’s the goal of CLARITY Undiagnosed, an international challenge launching today in which scientific teams can compete to provide answers for five families with undiagnosed conditions. (Deadline for applications: June 11).
A:SCID is a group of disorders that compromise the blood’s T cells, a key component of the immune system that helps the body fight common viral infections, other opportunistic infections and fungal infections. T-cells are also important for the development of antibody responses to bacteria and other microorganisms. A baby born with SCID appears healthy at birth, but once the maternal antibodies that the baby is born with start to wane, the infant is at risk for life-threatening infections. Unless diagnosed and treated—with a stem cell transplant from a healthy donor or a more experimental therapy like gene therapy—babies with SCID typically die before their first birthday.
Our genes can mutate at any point in our lives. In rare cases, a mutation randomly occurs in a single cell of an embryo and gets carried forward only in the descendants of that particular cell, leaving its mark in some tissues, but not in others. This pattern of mutation, called somatic mosaicsm, can have complicated consequences down the road.
From new longer-acting drugs to promising gene therapy trials, much is changing in the treatment of hemophilia, the inherited bleeding disorder in which the blood does not clot. Hemophilia Awareness Month comes at a time of both progress and remaining challenges.
1. Many more treatment products are being introduced, including some that last longer.
People with hemophilia lack or have defects in a “factor”—a blood protein that helps normal clots form. Of the approximately 20,000 people with hemophilia in the U.S., about 80 percent have hemophilia A, caused by an abnormally low level of factor VIII, and most of the rest have hemophilia B, caused by abnormally low levels of factor IX. Many patients with severe hemophilia give themselves prophylactic IV infusions of the missing factor to prevent bleeding (which otherwise can lead to crippling joint disease when blood seeps into the joint and enzymes released from blood cells erode the cartilage).
Hemophilia factors traditionally have such a short half-life that we tend to treat patients every other day with factor VIII and twice a week with factor IX. The first two longer-lasting products came onto the market within the past year, and more are on the way. So now, with factor IX, it is possible to get an infusion just once a week and not bleed. This is really changing how we think about the disease. So far, the longer-acting factor VIII products are not yet long-lasting enough to make as dramatic a difference in the frequency of infusions. And creating really long-acting factors remains a challenge.
Historically, the starting point for making a rare disease diagnosis is the patient’s clinical profile: the set of symptoms and features that together define Diamond Blackfan anemia (DBA), Niemann-Pick disease or any of a thousand other conditions.
For example, anemia and problems absorbing nutrients are features of Pearson marrow pancreas syndrome (PS), whereas oddly shaped fingernails, lacy patterns on the skin and a proneness to cancer point to dyskeratosis congenita (DC).
The resulting diagnoses give the child and family an entry point into a disease community, and is their anchor for understanding what’s happening to them and others: “Yes, my child has that and here’s how it affects her. Does it affect your child this way too?”
But as researchers probe the relationships between genes and their outward expression—between genotype and phenotype—some families are losing that anchor. They may discover that their child doesn’t actually have condition A; rather, genetically they actually have condition B. Or it may be that no diagnosis matches their genetic findings.
What does that mean for patients’ care, and for their sense of who they are?