Therapeutic Management of Menkes Disease and Related Copper Transport Disorders
The only currently available treatment for Menkes disease, subcutaneous copper histidinate injections, is successful only in patients with ATP7A gene mutations that do not completely corrupt ATP7A copper transport function (estimated 20-25% of affected patients) and when started at a very early age (first month of life). The combination of viral gene therapy with copper injections provides working copies of the ATP7A copper transporter into the brain, together with a source of the substrate (copper) needed for proper brain growth and clinical neurodevelopment.
Codon-optimized nucleic acids encoding a reduced-size ATP7A protein and compositions of AAV vectors were discovered by NICHD researchers along with methods of administering this therapy. Human P-type ATPase copper-transporting ATPase 1 (ATP7A) transports copper from enterocytes (where it is taken up from dietary copper) into the blood. ATP7A also mediates passage of copper across the blood-cerebrospinal fluid (CSF) barrier and the blood-brain barrier. In Menkes disease and occipital horn syndrome (OHS), copper accumulates in intestinal cells and less copper is absorbed into the blood, resulting in restricted copper supply to other tissues, particularly the brain. Death in infancy or early childhood is a common consequence. Therapeutic delivery of the copper transport protein via an AAV vector, combined with subcutaneous copper histidinate treatment will relieve the copper deficiency to the brain and permit normal neurological development and function.
Competitive Advantages:
Provides working copies of the ATP7A copper transporter into the brain, together with a source of the substrate (copper) needed for proper brain growth and clinical neurodevelopment.
Commercial Applications:
- Treatment of Menkes Disease, Occipital Horn Syndrome, and of ATP7A-related distal motor neuropathy
Patents
- US
Provisional (PRV) 62/244,594
Filed on 2015-10-21
Status: Abandoned - Patent Cooperation Treaty
(PCT) PCT/US2016/058124
Filed on 2016-10-21
Status: Expired - US Patent 10,988,778
Filed on 2018-04-18
Status: Issued - European Patent
National Stage 16794111.1
Filed on 2016-10-21
Status: Issued - Australia
National Stage 2016341983
Filed on 2016-10-21
Status: Issued - Canada
National Stage 3001574
Filed on 2016-10-21
Status: Pending - China
National Stage 201680074686.6
Filed on 2018-06-20
Status: Issued - Japan
National Stage 2018-520100
Filed on 2016-10-21
Status: Issued - Japan
Divisional (DIV) 2020-218556
Filed on 2016-10-21
Status: Abandoned - US Patent 12,173,306
Filed on 2021-03-30
Status: Issued - Austria
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - Belgium
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - Switzerland
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - Czech Republic
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - Germany
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - Denmark
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - Spain
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - France
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - United Kingdom
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - Hungary
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - Ireland
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - Italy
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - The Netherlands
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - Norway
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - Poland
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - Portugal
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - Sweden
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued - Turkey
European patent (EP) 16794111.1
Filed on 2016-10-21
Status: Issued
Collaborations
- Licensing