Novel gene Therapy Shows Promise Against Relapsed Medulloblastoma
Researchers at Uppsala University have developed a novel gene therapy technique targeting medulloblastoma, the most common malignant brain tumor in children, with the aim of preventing relapse and reducing treatment side effects. The approach focuses on exploiting a protein, SOX9, that accumulates in cancer cells during tumor recurrence.
While current treatments – surgery, radiation, and chemotherapy – are effective in approximately 75% of cases, they can cause significant long-term side effects due too their impact on developing brains. Relapse, often linked to increased mortality, occurs when cancer cells develop resistance to these standard therapies.
The Uppsala team, led by researcher Fredrik Swartling, engineered a virus to deliver a specific DNA sequence linked to a tumor-killing enzyme directly into cancer cells. This virus targets cells with high levels of SOX9, a protein previously identified by Swartling’s group as accumulating during relapse. The SOX9 sequence acts as a guide,ensuring the enzyme is delivered specifically to the cancerous cells.
“Our approach utilizes a ‘Trojan horse’ mechanism,” explains Swartling. “The virus infects tumor cells and introduces the SOX9 sequence linked to an enzyme. We allow a few days for the SOX9 to bind within the cells where it’s concentrated,then initiate treatment with an antiviral drug,ganciclovir,wich activates the enzyme to destroy the dividing cancer cells.”
Testing in cells derived from medulloblastoma patients and in animal models demonstrated the treatment’s effectiveness. Importantly, ganciclovir successfully penetrated brain tumors, and the therapy showed synergistic effects when combined with radiotherapy.
Researcher Tina Lin notes that improving the efficacy of radiation therapy coudl allow for lower doses, possibly minimizing side effects for young patients. ”If our treatment enhances radiation’s effectiveness, we may be able to reduce the radiation dosage, leading to fewer long-term consequences for children undergoing treatment.”
The research team is now focused on developing a clinically viable version of the gene therapy for use in patients. Eight gene therapies based on similar viral vectors are already approved for clinical use. Swartling anticipates initiating clinical trials within two to three years, contingent on securing sufficient funding.
“This type of gene therapy remains expensive,” Swartling acknowledges. “Though, the virus we’ve utilized has demonstrated both safety and a remarkable ability to reach cancer cells located deep within organs, including the brain.”
