Menkes disease is a lethal genetic disorder that prevents the brain and other parts of the body from getting enough copper. In patients with Menkes syndrome, the lack of copper damages the brain and nervous system and the structure of bone, skin, hair, and blood vessels. Infants develop normally for the first few months before symptoms appear. With newborn screening test for the disease currently unavailable, early detection is difficult, and most affected children die within the first few years of life.
Very early treatment with daily copper injections may help stop brain degeneration and prolong survival. But survivors, and patients with a milder form of the disease called “occipital horn syndrome”, will still have ongoing symptoms, such as dizziness and fainting spells caused by low levels of norepinephrine, a natural chemical produced by nerve cells that both acts as a hormone and transmits nerve and brain signals.
A group of researchers in the Unit on Human Copper Metabolism, in the Division of Intramural’s Molecular Medicine Program, used a mouse model of Menkes disease to investigate whether a drug called L-DOPS could improve norepinephrine levels in these patients. L-DOPS can cross the blood-brain barrier and be converted into norepinephrine. The researchers injected L-DOPS or a placebo into mutant and normal mice at ages 8, 10, and 12 days. After the final injection, the researchers examined the mice’s brains. As expected, untreated mutant mice had low levels of norepinephrine. Mice treated with L-DOPS, both normal and mutant, had significantly higher levels of norepinephrine.
The researchers concluded that L-DOPS treatment, combined with other therapies, could benefit Menkes disease survivors and occipital horn syndrome patients (PMID: 23224983).