Rare neurological disease shines light on health of essential nerve cells

Ian Duncan is a Scotsman with the iron discipline and stamina of a competitive marathoner, triathlete and cross-country skier. As a neuroscientist at the School of Veterinary Medicine at the University of Wisconsin-Madison, he's applied his tenacity to a rare genetic disorder.

Known as Pelizaeus Merzbacher disease or PMD, it's a devastating neurological condition that, in its most severe form, kills infants weeks after birth.

Thirty years ago, Duncan noticed a genetic mutation in dogs that was practically identical to the disease in humans. Now, in the online edition of the journal Neurobiology of Disease, Duncan has laid out the results of his marathon pursuit of PMD.

His work underscores the benefits of patience and persistence in the discovery of unexpected results that may point toward new therapies.

Like multiple sclerosis, PMD is a disease that interferes with myelin, the insulation needed for normal communication in the nervous system. The genetic mutation that blocks the formation of myelin is found on the X chromosome, so the disease occurs only in males.

Studies of the dogs are crucial, Duncan says, since PMD is so rare in humans - occurring in one male birth in roughly 200,000.

Duncan says his studies have yielded discoveries that could help fight the grievous illness.

What is Pelizaeus-Merzbacher disease?

Pelizaeus-Merzbacher disease is an inherited condition involving the brain and spinal cord (central nervous system). This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are characterized by degeneration of myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. Pelizaeus-Merzbacher disease is caused by an inability to form myelin (dysmyelination). As a result, individuals with this condition have impaired intellectual functions, such as language and memory, and delayed motor skills, such as coordination and walking. Typically, motor skills are more severely affected than intellectual function; motor skills development tends to occur more slowly and usually stops in a person's teens, followed by gradual deterioration.

Pelizaeus-Merzbacher disease is divided into classic and connatal types. Although these two types differ in severity, their features can overlap.

Classic Pelizaeus-Merzbacher disease is the more common type. Within the first year of life, those affected with classic Pelizaeus-Merzbacher disease typically experience weak muscle tone (hypotonia), involuntary movements of the eyes (nystagmus), and delayed development of motor skills such as crawling or walking. As the child gets older, nystagmus usually stops but other movement disorders develop, including muscle stiffness (spasticity), problems with movement and balance (ataxia), and involuntary jerking (choreiform movements).