Novel gene Therapy Shows Promise Against Relapsed Medulloblastoma
Researchers at Uppsala Universityโ 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 โaccumulates in cancer cells โคduring tumor recurrence.
While current treatments – surgery, radiation, and chemotherapy – are effective in approximately 75% of cases, โthey โcan cause significant long-term sideโฃ effects due too โฃtheir impact on developing brains. โขRelapse, often linked to increased mortality, โคoccurs when cancer โฃcells 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 โคa tumor-killing enzyme directly into cancer cells. This โvirus targets cells with high levels of SOX9, a protein previously identified by Swartling’sโ group as accumulating during relapse. Theโ SOX9 sequence acts โas a guide,ensuringโฃ the enzyme is delivered specifically to the cancerous cells.
“Ourโ approach utilizes a ‘Trojan horse’ mechanism,” explains Swartling. “The virus infects tumor cells and introduces the SOX9 sequence linked to an enzyme. We allow aโ few days for the SOX9 to bind within theโค cells where it’s concentrated,then initiate treatment with an antiviral drug,ganciclovir,wich activates the โenzyme to destroy the โขdividing cancer cells.”
Testingโฃ in cells derived from medulloblastoma patients โand in animal โmodels demonstrated the treatment’sโฃ effectiveness. Importantly, ganciclovir successfully penetrated brain tumors, and theโข therapy showed synergistic effects whenโข 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. โ”If our treatment โฃenhances radiation’s effectiveness, โwe may beโ able to โขreduce the radiation dosage, leading to fewer long-term consequences for children undergoing treatment.”
The โคresearch โteam is โคnow focused on developing a โฃclinically viable version of the gene therapy for use in patients. Eight geneโข therapiesโ based on similar viral vectors are already approved for clinical use. Swartling anticipates initiating clinical trials within two to three years, contingent on securing โsufficient funding.
“This type of gene therapy remains expensive,” Swartling acknowledges. “Though, theโ virus we’ve utilized โคhasโ demonstrated both safety and a remarkable ability to reach cancer cells โlocated deep within organs, โincluding the brain.”
