GBA gene therapy (PR001)

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Prevail Therapeutics, bought by Eli Lilly in 2021. The trial, PROPEL (NCT04127578), is a Phase 1/2a study; its sites have included the US and Israel.

What happened

Mutations in GBA1 are the most common genetic risk factor for Parkinson's (landmark 16); they lower the activity of the enzyme GCase, which in turn may encourage alpha-synuclein to clump (landmark 35). PR001 uses a harmless virus (AAV9) to deliver a working copy of the gene to brain cells, as a single injection into the cisterna magna (the fluid space at the base of the skull). PROPEL began on 3 January 2020 and was originally planned as a sham-controlled study of 16 people (Alzforum). In August 2020 Prevail reported serious adverse events in the first treated patient, linked to an immune response to the viral vector and resolved with immune-suppressing drugs. The trial became open-label, with no sham arm, with a larger planned enrolment and extra immunosuppression (six methylprednisolone pulses over 3 months, sirolimus as back-up). It now has two dose levels, and participants have moderate to severe disease (Hoehn and Yahr stage III-IV) and at least one pathogenic GBA1 mutation. In April 2024 Lilly said it stopped the childhood Gaucher disease study while the adult Gaucher and Parkinson's trials continued. The registry, last updated 13 October 2026, shows PROPEL as active, not recruiting, with an estimated 32 participants, a 5-year design and estimated completion in August 2031. The main measures are safety and immune responses to the vector and to GCase. No safety or efficacy data from PROPEL were found.

Why it moved us toward a cure

It is the first attempt to fix, rather than just activate, the GBA pathway. Unlike the small-molecule drugs that failed (landmark 69), a gene copy could in principle provide lasting enzyme. The immune reaction shows a specific risk for brain gene therapy.

Outcome

Open. Whether adding GCase changes the course of GBA-linked Parkinson's is untested in controlled form.

Sources

• Alzforum therapeutics entry for PR001 · Registry copy, NCT04127578 (SCGE) · CGTLive, Dec 2024
• ClinicalTrials.gov NCT04127578 (read via API, 19 Oct 2026)
• Not yet verified: actual enrolment (sources say 16, 20, 24 and 32 at different dates); dose amounts; the Alzforum page was last updated in 2023, so the 2024 events come from its reference to an investor call.