Marley Mansour, an 11-year-old from Rowlett, Texas, is about to make history as the first person in the world to receive a treatment for the ultra-rare genetic disorder NARS1. Diagnosed in early 2023 after years of uncertainty, Marley finally has a path forward through a pioneering therapy.
Understanding NARS1
NARS1 (asparagine-tRNA synthetase) plays a critical role in protein synthesis. Mutations in this gene disrupt the body’s ability to produce functional proteins, leading to a variety of symptoms, including developmental delays, seizures, and motor challenges. Marley is among fewer than 100 people globally identified with this condition, according to Dr. Kaitlin Batley, assistant professor of pediatrics and neurology at UT Southwestern Medical Center.
Her specific mutation is classified as a “toxic variant,” which means her body produces a harmful version of the protein. She carries one healthy gene and one defective gene, causing her to generate both normal and abnormal proteins. This dual production severely impacts her neurological and physical development.
A Tailored Genetic Therapy
Marley’s treatment, antisense oligonucleotide therapy (ASO), is a promising genetic approach designed to silence the defective RNA. Developed by n-Lorem, a California-based nonprofit, the therapy uses short, synthetic DNA sequences to target and neutralize the faulty genetic material.
“The goal is to suppress the bad RNA, so only the good RNA remains,” explained Dr. Stanley Crooke, CEO of n-Lorem. “That way, her body can produce only the functional protein.”
As reported by Medical Xpress, ASO therapy is gaining recognition for its potential to address ultra-rare genetic mutations with high precision. The FDA has approved this investigational treatment specifically for Marley’s mutation, marking a breakthrough in personalized medicine.
Delivering the Treatment
Doctors will administer the ASO therapy via spinal tap. This direct method delivers the treatment to Marley’s central nervous system, where it can begin correcting the protein imbalance. The therapy aims to ease her severe communication difficulties and alleviate symptoms of peripheral neuropathy.
“Communication is a big struggle for her,” said her mother, Kayla Mansour. “She can’t tell us where it hurts. That’s terrifying for us as parents.”
The Road Ahead
Although the therapy offers new hope, the journey comes with emotional and financial challenges. The Mansour family must shoulder significant out-of-pocket expenses, as insurance does not cover costs associated with clinical trial participation. Over the next two years, their expenses are expected to exceed six figures.
Dr. Crooke estimated that each ASO treatment costs around $1.2 million. N-Lorem covers the cost of developing and supplying the drug for life through donations, grants, and partnerships. However, families remain responsible for hospital fees and related expenses not reimbursed by insurance.
A New Era in Rare Disease Treatment
N-Lorem, founded by Crooke, focuses exclusively on creating individualized ASO therapies for “nano-rare” patients—those with conditions affecting fewer than 30 people worldwide. Since 2022, the organization has evaluated over 300 applications, accepted more than 140 patients, and treated 15 with customized therapies.
“We don’t promise miracles,” said Crooke, “but we do promise to never stop trying. Safety is always our top priority.”
Marley’s case could become a beacon for others with similar genetic mutations. By opening the door to personalized, mutation-specific treatments, her journey represents a significant step toward broader therapeutic possibilities for those living with ultra-rare disorders.