FDA approves study of SNUG01 gene therapy for ALS patients
Therapy is designed to increase TRIM72, a neuroprotective protein
The U.S. Food and Drug Administration (FDA) has authorized Sineugene Therapeutics to begin a Phase 1/2a trial of its experimental gene therapy, SNUG01, in people with amyotrophic lateral sclerosis (ALS).
The global trial will assess the treatment’s safety, tolerability, and preliminary efficacy through a dose escalation and expansion protocol in adults with ALS, according to a company press release.
ALS is caused by the progressive dysfunction and death of motor neurons, the nerve cells that control voluntary movements. While the exact mechanisms that lead to the loss of these neurons aren’t fully understood, a combination of genetic, environmental, and lifestyle factors is thought to contribute to the risk of developing the disease.
SNUG01 is a first-in-class targeted gene therapy that’s designed to increase the levels of TRIM72, a protein with neuroprotective properties that was identified through research at Tsinghua University in China. The therapy uses a modified adeno-associated virus (AAV) carrier to deliver the human TRIM72 gene to patient cells. It’s administered via an intrathecal injection, that is, one given into the spinal canal.
Unlike other gene therapies that target specific genetic mutations, SNUG01 leverages multiple neuroprotective mechanisms that allow it to be used to treat most ALS patients, addressing an urgent unmet need in this population, according to Sineugene.
TRIM72 and ALS progression
In preclinical studies at Tsinghua University, researchers demonstrated that AAV-mediated neuronal expression of TRIM72 can slow ALS progression and extend the lifespan of ALS mouse models.
TRIM72 was also able to counteract disease mechanisms in ALS by reducing oxidative stress, restoring mitochondrial activity, inhibiting neuroinflammation, and improving neuronal membrane repair. Oxidative stress is a type of cellular damage driven by the excessive accumulation of toxic oxidant molecules. Mitochondria are small compartments within cells responsible for producing energy.
In a completed investigator-initiated trial, SNUG01 was found to have a favorable safety and tolerability profile. The therapy also showed early signs of efficacy in both functional clinical assessments and key neurodegeneration biomarkers. In a separate compassionate use study (ChiCTR2400085764), SNUG01 slowed and stabilized disease progression in an ALS patient who’d been followed for more than a year.
A second investigator-initiated trial (NCT06645197) that was launched earlier this month at Peking University Third Hospital, will further explore the safety and therapeutic efficacy of different doses of SNUG01 in ALS patients.
About the Author
