Awarded Grants

Awarded Grants

MDBR, AT Million Dollar Bike Ride MDBR, AT Million Dollar Bike Ride

SKIP-AT: a comprehensive, systematic platform approach for targeted exon skipping of ATM

Matthis Synofzik

Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany

$53,240.00

Awardee: Matthis Synofzik

Institution: Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany

Grant Amount: $53,240.00

Funding Period: February 1, 2024 - January 31, 2025

Summary:

We will develop and validate a systematic, comprehensive platform approach for targeted exon skipping of constitutive ATM exons. For this, we can directly leverage and extend our established, scalable platform for the development of patient-specific antisense oligonucleotides (ASOs) for ATM - with already proven efficacy from preclinical to clinical translation in our hands. Our ATM exon-skipping approach will demonstrate and validate a systematic experimental path that will allow to provide the genomic medicine field with the urgently warranted comprehensive knowledge on which exons of the ATM gene can be (ASO-)skipped - and in fact even allows to already prepare the most promising skippable exons for clinical ASO treatment development.

Read More
MDBR, AT Million Dollar Bike Ride MDBR, AT Million Dollar Bike Ride

PET Radiotracer development based on existing ATM-inhibitors

Jacob Hooker

Massachusetts General Hospital

$116,172.00

Awardee: Jacob Hooker

Institution: Massachusetts General Hospital

Grant Amount: $116,172.00

Funding Period: February 1, 2023 - January 31, 2024

Summary:

Ataxia-telangiectasia (A-T) is a rare autosomal recessive genetic disease that involves progressive neurodegeneration (cerebellar atrophy), immune deficiency, lung problems and a strikingly high increased risk of cancer. Children with A-T start life with almost normal motor function but then lose muscle control and balance so that speech, eye-tracking and swallowing become much more difficult, and they usually need to use wheelchairs by age nine. Multiple therapeutic strategies are being pursued clinically but there is no direct functional restoration measure of ATM, the PIKK (PI3K-like protein kinase) available for therapeutic monitoring in the brain. Our hypothesis is that functional ATM presents a binding site for a small-molecule-based ATM-inhibitor and thus binding of the inhibitor can be used as a proxy measure of the functional concentration of ATM. By labeling ATM-inhibitors with a positron emitting isotope, it thus may be possible to image the amount of functional ATM in the brain using positron emission tomography. We will synthesize and radiolabel a series of ATM-inhibitors for evaluation of this functional biomarker concept.

Read More
MDBR, AT Million Dollar Bike Ride MDBR, AT Million Dollar Bike Ride

Development of at-home speech and wearable sensor biomarkers for ataxia-telangiectasia

Annopum Gupta

Massachusetts General Hospital and Harvard Medical School

$129,898

Awardee: Anoopum Gupta

Institution: Massachusetts General Hospital and Harvard Medical School

Award Amount: $129,898

Funding Period: February 1, 2021 - January 31, 2022

Final Report Lay Summary:

Promising disease-modifying therapies are being developed for ataxia-telangiectasia and other pediatric neurological diseases, but current assessment tools are very insensitive at determining efficacy, resulting in large and expensive trials. This project aimed to develop precise motor outcome measures, using inexpensive and widely accessible digital technologies, that can sensitively determine if a therapy is effective in children of a l ages. We co lected continuous wrist accelerometer data from 31 individuals with ataxiatelangiectasia and 27 controls aged 2-20 years old. Longitudinal wrist sensor data were colected in 14 ataxia-telangiectasia participants and 13 controls. A novel algorithm was developed to extract wrist movement patterns the accelerometer data. Wrist sensor features were compared with caregiver-reported motor function and ataxia severity on neurologist-performed ataxia rating scales. We found that these wrist sensor-based features show strong potential as novel disease measures for clinical trials: they demonstrate high reliability, correlate with clinician assessments of motor severity and caregiverreported motor function, and show potential to sensitively quantify disease progression. By passively measuring everyday activity, the information obtained can be more ecologica ly valid and comprehensive than task-specific measurements and is applicable in young children as we l in older, non-ambulatory individuals.

Read More