Positive Preclinical Data Support FTD-GRN Gene Therapy Study Initiation


AviadoBio announced the initiation of the phase 1/2 ASPIRE-FTD clinical trial earlier in October.

Intrathalamic delivery of AVB-101, an investigational gene therapy for the treatment of frontotemporal dementia with disease-causing mutations in the GRN gene (FTD-GRN) was well tolerated and exhibited biodistribution of progranulin (PRGN) expression in the brain in non-human primates.1

The preclinical data were presented by Carlos Miranda, PhD, vice president head, preclinical research, AviadoBio, at the 30thAnnual Congress of the European Society of Gene & Cell Therapy (ESGCT), held October 24-27 in Brussels, Belgium.

“We are excited to present at ESGCT our preclinical data on a novel gene therapy for people with FTD-GRN. Infusion of AVB-101, containing the GRN gene, directly into the thalamus boosts progranulin protein production and secretion into the cortex. This approach has the potential to restore progranulin protein levels throughout the brain and address the needs of patients with FTD-GRN,” Christopher E. Shaw, MBBS, MD, professor of neurology, King’s College London and chief scientific officer and cofounder, AviadoBio, said in a statement.1 “As we begin enrollment in our Phase 1/2 ASPIRE-FTD trial, these data reinforce our belief in AVB-101 as a potential one-time, disease-modifying treatment for patients with this devastating disease.”

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The new preclinical data showed that all evaluated doses of intrathalamic delivery of AVB-101 were well-tolerated in nonhuman primates with no mortalities or observable clinical adverse events. Human PRGN was most abundant in the thalamus and detected throughout the brain, including in the temporal and frontal lobes which are severely affected by FTD-GRN. Gene expression was limited to the central nervous system and vector genomes were minimal or undetectable in most visceral tissues. In cerebrospinal fluid, researchers observed a dose-dependent increase in PRGN levels.

The new preclinical data support the recently announced initiation of the phase 1/2 ASPIRE-FTD clinical trial evaluating AVB-101 in people with FTD-GRN.2 ASPIRE-FTD is an open-label, multi-center study designed to evaluate the safety and preliminary efficacy. AVB-101 will be delivered as a 1-time intrathalamic treatment delivered via a stereotactic neurosurgical procedure at expert neurosurgical centers throughout Europe and the United States.

"FTD is a devastating form of early-onset dementia and there are currently no disease-modifying treatments available," Lisa Deschamps, chief executive officer, AviadoBio, said in a statement.2 "The initiation of our company’s first clinical trial demonstrates our commitment to developing and delivering potential transformative gene therapies for those living with neurodegenerative disorders such as FTD."

AVB-101 is an adeno-associated virus vector gene therapy designed to deliver a functional copy of the progranulin (GRN) gene to restore progranulin protein levels in the brain.

"While it is known that progranulin protein supplementation is possible using gene therapy, effective brain distribution remains challenging primarily because of the brain’s anatomy," David Cooper, MD, chief medical officer, added.2 "Our aim is to use intrathalamic delivery to facilitate biodistribution of the PGRN protein to the areas of the cortex impacted by FTD. AVB-101 has already shown great promise in preclinical studies, and we now look forward to this important next step in its clinical development."

1. AviadoBio announces presentation of promising preclinical safety and biodistribution data of its gene therapy candidate AVB-101 for FTD-GRN at the Annual European Society of Gene and Cell Therapy Congress. News release. AviadoBio. October 24, 2023. https://www.businesswire.com/news/home/20231023315084/en/AviadoBio-Announces-Presentation-of-Promising-Preclinical-Safety-and-Biodistribution-Data-of-its-Gene-Therapy-Candidate-AVB-101-for-FTD-GRN-at-the-Annual-European-Society-of-Gene-and-Cell-Therapy-Congress
2. AviadoBio announces initiation of phase 1/2 clinical trial, ASPIRE-FTD, evaluating AVB-101 in people with frontotemporal dementia with GRN mutations. News release. AviadoBio. October 10, 2023. https://finance.yahoo.com/news/aviadobio-announces-initiation-phase-1-110000027.html
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