Since starting Cal's Foundation, we have watched many - too many - families live through the nightmare of losing a child. But, in their grief, some families discover that picking up the pieces means honoring their child by helping other families. Sharing your story and your loss with the world is, most assuredly, not for everyone, but, for those who find meaning and purpose in taking this path, it is crucial part of the grassroots effort that will advance research and care for the one hundred forms of leukodystrophy.
For Nick and Shanna Quimby, their son Gavin's legacy will be working to advance research for leukodystrophies, and metachromatic leukodystrophy in particular. On January 10th, 2016, the Quimbys established a research fund for Dr. Alessandra Biffi, the director of gene therapy at Boston Children's Hospital with a gift of $40,000. Plans are underway for G-Fest in August of 2016, a fundraising effort in the Quimby's hometown of Winona, Minnesota, that will support Dr. Biffi and build on this generous gift.
The Gavin Quimby Research Fund will be used to help Dr. Biffi develop more efficacious treatments for leukodystrophies, with a particular emphasis on improving gene therapy's potential benefit to the central nervous system for children affected by metachromatic leukodystrophy and other related disorders. Dr. Biffi and her team also want to develop treatment options for children who have already shown symptoms of the disease.
Dr. Biffi's leadership at Boston Children's will bring exciting new opportunities since her research is spearheading "a renaissance" in "gene fixing" technology. Before coming to Boston Children's, the 42 year old Biffi worked at The San Rafaelle Telethon Institute for Gene Therapy (TIGET) in Milan, Italy. At TIGET, Dr. Biffi gained international acclaim for her efforts to treat children with metachromatic leukodystrophy.
Gene therapy treats disease by replacing the malfunctioning gene with a functional copy. Because researchers cannot inject naked DNA into cells, they use viruses - or vectors - to deliver the repaired gene - harnessing the viruses' ability to infiltrate the body’s cells.
The first success in gene therapy treatment came in the 1990s when doctors treated Ashanti De Silvan for SCID, or "Bubble Boy Disease," a genetic metabolic disorder that wipes out the immune system. Despite the early promise of gene therapy, the field suffered several setbacks. Many of the problems resulted from difficulties caused by the viruses used as the “delivery vehicle” or vectors for the treatments. In 1999, 18-year-old Jessie Gelsinger died after his immune system had an adverse reaction to the common cold virus used to deliver genes to correct his liver disease. In the aftermath of Gelsinger's death, all gene therapy trials in the US were halted and support for the entire industry withdrawn. In the following years, use of a type of virus called the retrovirus to deliver gene therapy to patients for various immune disorders caused nine cases of leukemia.
Dr. Biffi's work has addressed many of these early problems. And to treat patients with late-infantile onset metachromatic leukodystrophy, Dr. Biffi and her team found a way to repair the garbled version of the ARSA gene that affects cells in the nervous system that results in untreated patients losing the ability to walk, talk, eat and see.
Repairing these cells was a tricky task since these areas are heavily protected. To overcome these defenses, Dr. Biffi employed haematopoietic stem cells (HSCs), which are found in the bone marrow, as stealthy genetic couriers. A tiny number of these cells were harvested from the patient, loaded with benign viruses carrying a working copy of ARSA and put back into the bloodstream. These repaired cells either lodged in the bone marrow or traveled around the body in the blood, where they corrected defective cells in the nervous system by supplying the normal version of ARSA. Because these were stem cells, they were reproduced to form new blood cells that resurrected the dead lysomes in her patients to do their job of recycling machinery used by human cells to break down unwanted material.
Three years after treatment, normal ARSA levels were detected in the cerebrospinal fluid of the children she treated, a clear sign that the central nervous system had stabilized. Dr.Biffi's patients, all of whom have older siblings who have died from the disease, avoided the disease's most devastating effects and are attending school and enjoying normal childhoods. Experts such as the University of Pennyslvania's Dr. James Wilson and the University of Nebraska's Dr. William Rizzo describe Dr. Biffi's work in gene therapy as "miraculous" and "stunning."
Watch this video about Giovanni Price to learn more about Dr. Biffi's work for children with metachromatic leukodystrophy.
With this gift in honor of her son, Gavin, Shanna Quimby says she and her husband Nick will work for a future when "babies born with leukodystrophy never know they have leukodystrophy, and we can ensure they will get to grow up." Quimby believes, "this treatment will make miracles possible." Dr Biffi is so very grateful for the support of the Quimby family and the role they will play in her research. "This gift in honor of Gavin Quimby has enormous value to me and my collaborators since it testifies to the support of families who continue to inspire us. We will do our best to honor this gift and Gavin's memory and to use it to make progress in the treatment of children affected by leukodystrophies."