Current Program Status

We are preparing an Investigational New Drug (IND) application with the FDA to authorize the first dose of a personalized ASO therapy for GG.

We have an active clinical program with a lead ASO candidate, human neuronal efficacy data, and a regulatory filing in progress.

How a personalized ASO therapy works

Antisense oligonucleotides (ASOs) are short synthetic strands of genetic material designed to bind a specific sequence in a patient's own cells and correct a molecular deficit. Because each ASO is designed from a patient's exact mutation, this approach is inherently personalized — and it has been used to treat children with other ultra-rare genetic diseases, including Batten disease and SMA.

GG carries a pathogenic variant in the NAA15 gene (c.167delT, p.Lys56fs) that causes her cells to produce roughly 40% of the NAA15 protein a typical cell would make. Her ASO is designed to bind the 5' untranslated region of the NAA15 messenger RNA and restore normal protein levels — without altering her DNA.

What we've accomplished

Lead drug candidate identified. After screening a library of ASO compounds in GG's own patient-derived neurons, we identified our lead candidate. At our primary test dose, it substantially increased the level seen in untreated GG neurons — a meaningful restoration in cells that carry her exact mutation.

Active studies

Our IND-enabling work is currently running across three parallel tracks:

Functional efficacy — iXCells Biotechnologies, San Diego. GG's patient-derived glutamatergic neurons are being treated with our lead ASO across multiple dose levels and timepoints to establish dose-response, durability of effect, and optimal dosing schedule. A multielectrode array (MEA) study is measuring whether ASO treatment produces functional improvement in neuronal firing patterns.

Safety — Charles River Laboratories. Standard IND-enabling safety studies are underway to characterize the compound's toxicology profile.

Off-target transcriptomics — 626 Scientific, San Diego. A full RNA-sequencing study in human neural and microglial cell lines is profiling whether our ASO alters the expression of any unintended genes at therapeutic concentrations.

What comes next

When these studies are complete, we will compile the full IND package — chemistry, manufacturing and controls (CMC), pharmacology, toxicology, and clinical protocol — and submit it to the FDA.

The IND will be led by Dr. Olivia Kim McManus, GG's treating physician, who will serve as Principal Investigator. Dr. Kim-McManus brings an irreplaceable perspective to this filing: she is not only a physician overseeing the science, she knows GG. Having GG's own doctor as PI means the clinical protocol is built around a complete understanding of her medical history, her current care, and what treatment will mean for her specifically. She is also one of the most experienced physicians in this field, and we are so grateful for her care.

Support the program

Contact us at info@sweetgeejfoundation.org.