Email from Volunteer Chairman and Founder, Brad Margus:

As you know, to develop an urgently needed treatment for A-T, we’ve been eager to use a gene therapy approach called “antisense oligonucleotide” or “ASO” therapy to produce a functional ATM protein in children who have A-T.

While (with your help!) we’ve been steadily overcoming the financial challenges, Dr. Timothy Yu and a team of scientists at Harvard and Boston Children’s Hospital have been obtaining blood and skin cell samples from several A-T children and growing them in laboratory dishes. At the same time – exactly as we planned – the team has been designing and making numerous ASOs for each mutation and testing each one in the children’s cells to determine which ones most effectively silence the mutation, enabling the ATM protein to be made.

Even if you’re not a scientist, please glance at the graphic below that shows the results of an experiment performed on skin cells only a few hours ago:

In the red rectangle, you’ll see gel images from measuring ATM gene expression in untreated skin cells from a child affected by A-T. You see only one band corresponding to a mutant, nonfunctional ATM, because both of the child’s ATM genes are mutated.

To the immediate left of that red rectangle is the same test performed on cells from the child’s mother, who carries only one mutation and therefore makes an adequate level of ATM. Her column shows two horizontal bands (upper band = normal, lower = mutant).

And then on the right side of this graphic, you can see the results from testing the same child’s skin cells after treating them with several ASOs that Dr. Yu’s team have made. And – here’s the exciting part – in the green rectangle, you can see the results for “Oligo #8” which caused the child’s cells to produce about 55% of the normal level of ATM! That’s a lot, and it could be enough to make a cell function pretty much normally.

We can’t test what clinical effect this “ASO #8” will have in a living child for many more months, as a lot more functional and safety studies need to be done before we seek approval to deliver it into the child’s brain. But we’ve taken a huge step forward by identifying an ASO that works in the child’s cells!


Dr. Timothy Yu

We can’t thank Dr. Yu and his team – including April Hu, Jinkuk Kim, Diana Chin, Renata DiDonato and Aubrie Soucy – enough for how hard they’re working to overcome every obstacle and to advance an effective, safe ASO for A-T into the clinic. They’re giving us great hope.

More soon,
Brad Margus

P.S. – A note to A-T families seeing this email note:
ASOs won’t work for all kids with A-T. But besides ASOs, the A-T Children’s Project is now exploring other types of gene therapy. For example, we’ve just started supporting a UK researcher who is developing a “non-viral” approach to gene therapy (you’ll hear more about this soon), and we’re also in discussions with several companies about applying their gene-editing and gene-regulation technologies to A-T. Each of these approaches may expand the number of A-T kids we can help.

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