David Dimmock, MBBS, on a Promising Case Study of Ultra-Rare, AI-Guided, ASO Development
The chief medical officer at Creyon Bio discussed findings from a treated patient with a TNP02 missense mutation.
“We’re at the point now, we're very confident that the drug is working, because every time we give the drug, the child gets dramatically better, but unfortunately, it seems to be wearing off, and so we're in the process of working out what safety data we need to persuade everybody that it would be more appropriate to dose this child more frequently.”
An antisense oligonucleotide (ASO) therapeutic demonstrated proof-of-concept for Creyon Bio’s AI discovery platform in a case study of a single patient with a de novo heterozygous pathogenic variant causing a missense change in TNPO2. The produced ASO knocked down an allele selective toxic Transportin-2 (TNPO2) protein, the target of which was informed using Creyon'd AI model. The patient was dosed within 1 year of initiating the project with up to 3 doses of up to 40 mg.
The child experienced a dramatic clinical benefit, with reductions in seizure frequency subsequent to the second dose and regained developmental milestones. The child also developed new skills following the third dose. Between doses, clinical benefit would wear off and improvements would regress, demonstrating a need to redose with the ASO. The child has received 3 doses so far and investigators are anticipating the next dose.
CGTLive® spoke with David Dimmock, MBBS, chief medical officer at Creyon, to learn more about how the case study. He overviewed the disease pathology of the patient with the TNP02 missense mutation and the treatment course so far. He detailed the findings from the case study and the milestones that the child has received. He explained that definitive benefits have been observed with the ASO but the need to redose to maintain these benefits has also established.
REFERENCE
Dimmock DP, Bird L, Bouck A, et al. AI Enabled ASO Design Can Lead to Rapid Initiation of Treatment for an Ultra-Rare Disorder Leading to Allele Selective Knockdown of a Toxic Protein and Consequent Clinical Improvement. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #309
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