In a recent interview with Neurology Live, Aviado Bio chief medical officer David Cooper, MD, discussed the company’s Phase 1/2 ASPIRE-FTD trial. Dr. Cooper shared how the company’s AVB-101 gene therapy worked, and he outlined what criteria the study would need to meet to be successful.

The ASPIRE-FTD trial is focused on treating a specific type of genetic FTD caused by an inherited variation of the GRN gene. In FTD-GRN, the body’s ability to produce a protective protein called progranulin is suppressed, which can lead to abnormal accumulations of the protein TDP-43 in the brain, one of the proteins that forms abnormal accumulations in FTD.

“The goal of the study is to restore levels of progranulin in the brain, potentially slowing or stopping the progression of FTD-GRN,” Dr. Cooper said. “AVB-101 is delivered as a one-time treatment administered directly to the thalamus in an MRI-guided neurosurgical procedure.”

Dr. Cooper highlighted that delivering AVB-101 to the thalamus avoids the protective blood-brain barrier and pial membrane, helping to reduce the required dose. Pre-clinical studies not only showed that this method of administering the gene therapy was safe, but that AVB-101 can restore progranulin levels to the brain cortex.

Reflecting on what the ASPIRE-FTD trial would need to accomplish to be considered successful, Dr. Cooper noted three main goals:

• Demonstrate the safety of AVB-101 as a one-time FTD-GRN treatment.
• Identify a dosage that restores progranulin levels.
• Evaluate the potential impact of AVB-101 on the progression of FTD over a 5-year follow-up period.

Dr. Cooper acknowledged that FTD is a challenging disease to work with, which he said is why the unmet need remains high. However, he noted that AviadoBio’s approach has the advantage of being directly administered to the brain, which resolves some challenges associated with treatment.

“We are confident that targeted delivery of gene therapy will be a game-changer that overcomes the challenges of both crossing the blood-brain barrier and the unwanted systemic exposure that comes with administration into the cerebrospinal fluid (CSF),” Dr. Cooper said. “Delivering gene therapies either directly into the brain itself or to the CSF that surrounds it puts the gene therapy on the brain side of the blood-brain barrier. Putting the gene therapy directly into the brain has the advantage of the therapy staying in the brain.”

Speaking of the potential of gene therapies, Dr. Cooper also noted, “The difference in patients’ lives could be huge, as we’ve seen recent gene therapy approvals that are changing treatment paradigms. By replacing or modifying gene function, disease progression can be halted or potentially even prevented.”

The ASPIRE-FTD opened its first US trial site in July at Ohio State University’s Wexner Medical Center. The trial is currently recruiting people between 30-75 years old who carry a pathogenic GRN mutation and show symptoms of either behavioral variant FTD or primary progressive aphasia. For more information on ASPIRE-FTD, visit the clinical trial’s webpage or its clinicaltrials.gov page.

Are you interested in participating in research? Join the FTD Disorders Registry to not only receive updates on participation opportunities, but to also contribute your lived experience with FTD, which will help guide researchers.