Copper Histidine Therapy for Menkes Diseases

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Early Copper Histidine Therapy in Menkes Disease

Conditions
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Kinky Hair Syndrome

Intervention / Treatment
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* Drug: Copper Histidine


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Copper histidine<br> | Drug: Copper Histidine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gross Motor Development at 36 Mos of Age or at Death (Mos) | This was measured based on the Denver Developmental Screening Test (DDST) I or II for age-appropriate gross motor development in apparently normal healthy subjects at specific ages (in months). The DDST employs a grid to assess expected developmental milestones in relation to chronologic age. | 36 months or death | 
| Fine Motor Adaptive Development at 36 Mos of Age or at Death (Mos) | This was measured based on the Denver Developmental Screening Test (DDST) I or II for age-appropriate fine motor development in apparently normal healthy subjects at specific ages (in months). The DDST employs a grid to assess expected developmental milestones in relation to chronologic age. | 36 months or death | 
| Personal-Social Development at 36 Mos of Age or at Death (Mos) | This was measured based on the Denver Developmental Screening Test (DDST) I or II for age-appropriate personal-social development in apparently normal healthy subjects at specific ages (in months). The DDST employs a grid to assess expected developmental milestones in relation to chronologic age. | 36 months or death | 
| Language Development at 36 Mos of Age or at Death (Mos) | This was measured based on the Denver Developmental Screening Test (DDST) I or II for age-appropriate language development in apparently normal healthy subjects at specific ages (in months). The DDST employs a grid to assess expected developmental milestones in relation to chronologic age. | 36 months or death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Somatic Growth Percentiles at 3 Years of Age (or at Age of Death) - Weight Percentile |  | 36 months or death | 
| Somatic Growth Percentiles at 3 Years of Age (or at Age of Death) - Length Percentile |  | 36 months or death | 
| Somatic Growth Percentiles at 3 Years of Age (or at Age of Death) - Head Circumference Percentile |  | 36 months or death | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Menkes, Copper, X-Linked, Neurodegeneration, ATP7A