ASO GENE THERAPY

Email from Volunteer Chairman and Founder, Brad Margus:

In the 24 years that I’ve been seeking support for our battle to treat A-T, I’ve always erred on the side of caution in describing what we hoped to achieve… maybe a slight improvement in a day-to day task like swallowing, or a small enhancement to some aspect of quality of life. But today, I’m bursting with excitement!

By applying a gene therapy approach called “antisense oligonucleotide” or “ASO” therapy, we may now have an opportunity to produce the functional ATM protein that is missing within the cells of children with A-T. I can’t be muted in my excitement today, because we may actually be able to stop the brutal disease process in at least one or two A-T kids this year!

Several ASO drugs have recently been approved by the FDA for other diseases that include Duchenne muscular dystrophy, spinal muscular atrophy and cytomegalovirus retinitis. Applying ASO therapy to A-T will involve making a drug that contains a short strand of RNA that will bind to the mutated site in the A-T child’s RNA so that the child’s cells avoid incorrect “RNA splicing” caused by the mutation. The drug will then be injected into the child’s spinal fluid so that it can reach the brain.

Initially, only the youngest A-T kids who have lost the fewest brain cells and who carry a certain type of mutation will be treated with this approach. In fact, a customized drug will be needed for each child. But despite these limitations, rescuing the first few children from this terrible disease will be the culmination of everything we have worked for. If we’re successful, we will then throw all of our resources and energy into addressing additional types of mutations and making the manufacturing faster and cheaper. Hopefully, we’ll eventually move onto many A-T patients, maybe even those as old as my A-T sons.

Since founding the A-T Children’s Project, we’ve focused primarily on treatments, with a cure in mind but always seeming so far away. And yet, here we stand, poised to leapfrog a symptomatic treatment and potentially give a full, normal, healthy lifetime to first a few, and then hopefully many more children born with A-T. I’m so grateful to you for previously supporting A-T research that has led us to this point.

To make this exciting next step happen, the A-T Children’s Project will need to spend $1.4 million over the next twelve months. Please, please consider joining Vicki and me in making a special donation and designating it for this initiative.

All the best,
Brad

Brad Margus
Volunteer Chairman and Founder

PS: If you’d like to learn more details about the technical approach, our planned budget, and milestones that we expect to achieve along the way, please let me know. Our trial will be led by Dr. Timothy Yu whose credentials include being a UC San Francisco-trained MD-PhD neurologist and geneticist, a Harvard Medical School professor, a Boston Children’s Hospital attending physician, and an associate member of the Broad Institute of MIT and Harvard. As a physician-scientist, Dr. Yu has experience testing new therapies in children and expediting interactions with regulatory authorities.

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