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J05 Interim results from cohort 1 of the double-blind, dose-escalation phase I/II clinical trial of amt-130 (HD-genetrx-1) for early-stage huntington’s disease (HD)
  1. Erin Furr Stimming1,
  2. Victor Sung2,
  3. Claudia Testa3,
  4. Sandra Kostyk4,
  5. Christopher A Ross5,
  6. Ali Samii6,
  7. Michael D Geschwind7,
  8. Deborah Hall8,
  9. Praveen Dayalu9,
  10. Russell Lonser10,
  11. Brad Elder10,
  12. Paul S Larson11,
  13. David L Cooper12,
  14. Marcie Clarkin12,
  15. Talaha M Ali12,
  16. Ricardo E Dolmetsch12,
  17. on behalf of the AMT-130-01 Investigators
  1. 1McGovern Medical School, Houston, Texas, USA
  2. 2University of Alabama School of Medicine, Birmingham, Alabama, USA
  3. 3University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
  4. 4Ohio State University Wexner Medical Center, Columbus, Ohio, USA
  5. 5Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  6. 6University of Washington Medical Center, Seattle, Washington, USA
  7. 7University of California, San Francisco, California, USA
  8. 8Rush University Medical Center, Chicago, Illinois, USA
  9. 9University of Michigan Medical School, Ann Arbor, Michigan, USA
  10. 10The Ohio State University College of Medicine, Columbus, Ohio, USA
  11. 11University of Arizona Banner UMC-Tucson, Southern Arizona VA Health Care System, Tucson, Arizona, US
  12. 12uniQure Inc., Lexington, MA, USA


Background Huntingtin (HTT) lowering therapies hold great promise to slow or halt neurodegeneration in Huntington’s disease (HD). AMT-130 is an investigational AAV5-based gene therapy that expresses an engineered microRNA to specifically bind to huntingtin exon 1, thereby lowering total HTT mRNA.

Aims We initiated a double-blinded first-in-human study to investigate AMT-130 in early-stage patients and here describe interim 12-month results from the low-dose cohort (NCT04120493).

Methods Inclusion criteria were DCL 3-4, TFC 9-13, ≥40 CAG repeats, and caudate/putamen volumes greater than a prespecified minimum. Participants received one-time AMT-130 administration using MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into six sites bilaterally (3/side) in the striatum, or a sham surgical procedure.

Results At baseline, ages of 10 enrolled participants in Cohort 1 ranged from 34-58 years (mean:49), historical CAG repeats from 41-44 (mean:42), CAP scores from 318-542 (mean:426), TFC from 10-13 (mean:11.9) and TMS from 7-23 (mean:13.3). At 12-months post-treatment, the most common treatment-emergent adverse event was transient post-procedural headache (70%). Two serious adverse events judged to likely be unrelated to AMT-130 were observed: an upper extremity DVT at an intravenous line site presenting 1-week post-procedure, and brief post-operative delirium; both resolved. At 12-months post-treatment, CSF NfL returned to near baseline levels following an initial increase and the mean CSF mHTT decreased 53.8% (range:44-71%) compared to baseline.

Conclusions Follow up of participants is ongoing. Cohort 1 interim data thus far supports the safety and tolerability of a one-time infusion of AMT-130 in patients with early-stage HD.

  • huntingtin lowering
  • clinical trial
  • AAV gene therapy
  • safety
  • biomarkers

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