Targeting NUDT21 siRNA Drugs for Patients With Refractory Retinoblastoma

Summary

Retinoblastoma (RB) is the most common intraocular malignancy in children, accounting for approximately 11% of all cancers diagnosed in children under the age of one. Although its incidence is relatively low-about 1 in 15,000 to 20,000 live births-RB has a high risk of intracranial metastasis via the optic nerve, often leading to poor prognosis in advanced cases.

Recent advances in administration routes, such as intravitreal and intra-arterial chemotherapy, have significantly improved eye preservation rates. However, these strategies are limited by cumulative retinal toxicity and drug resistance. In refractory cases, enucleation remains the only definitive treatment to prevent extraocular spread and death.

In light of these challenges, current research efforts are focused on developing novel targeted therapies that enhance anti-tumor efficacy while minimizing local toxicity. In this context, we introduce a first-in-class siRNA-based drug targeting NUDT21, which promotes tumor regression by modulating the 3'UTR tail of SMC1A, thereby suppressing tumor cell proliferation. Importantly, the siRNA drug selectively targets tumor cells, offering a favorable safety profile compared to conventional chemotherapeutic regimens.

Given that both the target (NUDT21) and the mode of administration (intraocular siRNA injection) are novel in retinoblastoma treatment, there is an urgent need for early-phase investigator-initiated clinical research. This study is therefore designed to assess the short-term safety and preliminary efficacy of NUDT21 siRNA in patients with refractory retinoblastoma, and to provide an evidence base for future large-scale clinical trials.

Conditions

• Retinoblastoma
• Refractory

Interventions

DRUG

Targeting NUDT21 siRNA drugs

It is performed for intravitreal chemotherapy.

Sponsors & Collaborators

• The Eye Hospital of Wenzhou Medical University

  collaborator OTHER

• Eye & ENT Hospital of Fudan University

  lead OTHER

Principal Investigators

• Chen Zhao, MD · Fudan Eye & ENT Hospital

• Kang Xue, MD · Fudan Eye & ENT Hospital

• Kang Zhang, MD · The Eye Hospital of Wenzhou Medical University

• Jiang Qian, MD · Fudan Eye & ENT Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

6 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-12-20

Primary Completion

2025-09-30

Completion

2025-09-30

Countries

• China

Study Locations