Twelve-year-old twins Luka and Mira began stumbling during simple games of tag—first a wobble, then a fall, then a diagnosis that left their parents searching for answers no doctor could give. They had a rare neurodegenerative disease caused by mutations in the DHDDS gene, a condition so obscure that until recently, families were told to brace for decline with no hope of intervention. But now, thanks to a breakthrough led by Dr. Irena Muffels and a pair of determined parents, a simple form of vitamin B3—nicotinamide mononucleotide, or NMN—is offering real hope. Using stem cells from patients like Luka and Mira, researchers grew miniature brain models in the lab, revealing not only how the disease progresses but also how to potentially stop it in its tracks.
DHDDS-related disease disrupts the production of dolichol, a lipid essential for attaching sugar molecules to proteins—like placing the right antenna on a satellite. Without it, proteins malfunction, brain cells falter, and over time, cholesterol builds up in astrocytes, impairing mitochondria and starving neurons of energy. "This accumulation builds over time, and this is why we think the disease progresses," Dr. Muffels explained at the European Society of Human Genetics conference. For families, that meant watching their children lose coordination, strength, and independence.
But the mini-brains—grown from patients’ own cells at the Icahn School of Medicine at Mount Sinai—revealed a lifeline. In collaboration with biotech company Perlara, researchers screened existing drugs and vitamins and found NMN not only rescued yeast models of the disease but also reversed key deficits in the human mini-brains. When families, desperate and informed, began sourcing NMN online, the results were striking: within a month, children walked more steadily, moved with greater fluidity, and regained energy. Tremors lessened. Progression slowed.
Today, 12 patients across the world are taking NMN, and an international clinical trial is launching to validate what families are already seeing. NMN, already under study for mitochondrial and Parkinson’s diseases, may have broad potential for disorders rooted in cellular energy failure. For the first time, families affected by DHDDS are not just waiting—they’re moving forward.
"They didn’t want to wait," Dr. Muffels said of the parents who sparked this research. Now, because of their urgency and the power of patient-driven science, others won’t have to.