Copper Histidine Therapy for Menkes Diseases
Copper Histidine Therapy for Menkes Diseases
Menkes Disease is a genetic disorder affecting the metabolism of copper. Patient with this
 disease are both physically and mentally retarded. Menkes disease is usually first detected
 in the first 2-3 months of life. Infant males born with the disease fail to thrive,
 experience hypothermia, have delayed development, and experience seizures. These infants also
 have characteristic physical features such as changes of their hair and face. Females may
 also have changes in hair and skin color, but rarely have significant medical problems.

 Appropriate treatment of Menkes Disease requires that the disease be diagnosed early and
 treatment started before irreversible brain damage occurs. The aim of treatment is to bypass
 the normal route of absorption of copper through the gastrointestinal tract. Copper must then
 be delivered to brain cells and be available for use by enzymes.

 Copper histidine is a copper replacement that can be injected directly into the body to avoid
 absorption through the gastrointestinal tract. However, studies have shown the genetic
 abnormalities causing Menkes disease cannot simply be corrected by copper replacement
 injections.

 The genetic abnormality causing Menkes disease can vary in its severity. Patients with a
 genetic abnormality that may still permit some production of the enzymes required to process
 copper may receive benefit from early treatment with copper replacement. However, patients
 with severe abnormalities of the genes responsible for copper metabolism may receive no
 benefit from copper replacement.

 The purpose of this study is to continue to evaluate the effects of early copper histidine in
 Menkes disease patients and to correlate specific molecular defects with responses to
 treatment.
Menkes disease is an X-linked recessive neurodegenerative disorder caused by defects in a
 gene that encodes an evolutionarily conserved copper-transporting ATPase (ATP7A). Several
 issues must be addressed in configuring therapeutic strategies for this disorder: (a)
 affected infants must be identified and treatment commenced very early in life before
 irreparable neurodegeneration occurs, (b) the block in intestinal absorption of copper must
 be bypassed, (c) circulating copper must be delivered to the brain, and (d) copper must be
 available to enzymes within cells that require it as a cofactor.

 Very early, pre-symptomatic therapy with copper injections has been associated with improved
 overall survival and, in some patients - based on their molecular defects, with vastly better
 neurological outcomes in comparison to the usual natural history of this disorder. The
 purpose of this study is to continue to provide early copper treatment to other newborn
 infants diagnosed as having Menkes disease.
-  INCLUSION CRITERIA:

 Newborn infants in whom Menkes disease is confirmed on biochemical or molecular grounds and
 in whom no neurological symptoms are present are eligible for enrollment in this study.

 EXCLUSION CRITERIA:

 Newly identified patients classified as symptomatic at the time of diagnosis, and affected
 individuals with mild phenotypes are not currently eligible for this clinical trial.