{"id":1215,"date":"2023-10-19T19:06:06","date_gmt":"2023-10-19T19:06:06","guid":{"rendered":"https:\/\/bcchrmicro.wpengine.com\/?page_id=1215"},"modified":"2026-04-30T22:03:52","modified_gmt":"2026-04-30T22:03:52","slug":"hld22-study","status":"publish","type":"page","link":"https:\/\/www.bcchr.ca\/biochemical-genetics\/projects\/hld22-study\/","title":{"rendered":"HLD22 study"},"content":{"rendered":"
\n\t
\n\t
\n\t
\n\t
\n\t<\/span>\n\tBiochemical Genetics Clinic<\/span><\/a><\/span><\/div>\n

HLD22 study<\/h1><\/div>\n
\n\t
\n\t<\/figure>\n<\/div>\n<\/div><\/div>\n<\/div>\n\n\n
\n\t
\n\t
\n\t

CLDN11-related hypomyelinating leukodystrophy (HLD22)<\/h2>

Mahmoud Pouladi, Principal Investigator
Sophia Gjervan, PhD Student
Oguz Ozgoren, PhD Student
Sylvia Stockler, Clinical Co-investigator
Simone Race, Genetic Counsellor & Coordinator<\/strong><\/p>

CLDN11-related hypomyelinating leukodystrophy (HLD22) is a newly described condition, causing developmental delay, spasticity and myelination deficit in the brain. CLDN11 encodes claudin-11, a tight junction protein enriched in oligodendrocytes, the myelinating cells of the central nervous system. <\/p>

The exact mechanisms underlying mutant claudin-11-mediated HLD are poorly understood, hampering efforts to develop effective therapies for this disorder.<\/p>

Our goal is to better understand the molecular, cellular, and neuropathological changes caused by mutant claudin-11 and to evaluate potential therapeutic strategies for this disorder. <\/p>

We are using a novel mutant claudin-11 knock-in (mcKI) mouse model, and patient-derived induced pluripotent stem cell (iPSC) lines to produce pre-clinical data to support therapeutic development for HLD22. To this end we are also collecting genotype and phenotype information as well as biological materials (PBMCs, fibroblasts) from newly diagnosed patients.<\/p>

Specific aims of our research are:
Aim 1<\/strong>: Comprehensive phenotypic characterization of mutant claudin-11 KI mice
Aim 2<\/strong>: Delineation of phenotypic abnormalities in oligodendroglia derived from patient iPSCs
Aim 3<\/strong>: Evaluation of silencing of mutant claudin-11 as a therapeutic strategy in mice and iPSCs<\/p>

References<\/h3>

Riedhammer KM, Stockler S, Ploski R, Wenzel M, Adis-Dutschmann B, Ahting U, Alhaddad B, Blaschek A, Haack TB, Kopajtich R, Lee J, Murcia Pienkowski V, Pollak A, Szymanska K, Tarailo-Graovac M, van der Lee R, van Karnebeek CD, Meitinger T, Kr\u00e4geloh-Mann I, Vill K. De novo stop-loss variants in CLDN11 cause hypomyelinating leukodystrophy<\/a>. Brain<\/em>. 2021 Mar 3;144(2):411-419. doi: 10.1093\/brain\/awaa410. Erratum in: Brain. 2021 Jun 22;144(5):e48. PMID: 33313762; PMCID: PMC7940174.<\/p>

Ozgoren OK, Sequiera GL, Ferrari Bardile C, Gjervan SC, Salman A, Lehman A, Turvey SE, Ross CJD, Stockler S, Pouladi MA. Generation of a human induced pluripotent stem cell line from a patient with hypomyelinating leukodystrophy 22 (HLD22)<\/a>. Stem Cell Res<\/em>. 2023 Sep;71:103174. doi: 10.1016\/j.scr.2023.103174. Epub 2023 Jul 28. PMID: 37531724.<\/p>

Gjervan SC, Ozgoren OK, Gow A, Stockler-Ipsiroglu S, Pouladi MA. Claudin-11 in health and disease: implications for myelin disorders, hearing, and fertility<\/a>. Front Cell Neurosci<\/em>. 2024 Jan 17;17:1344090. doi: 10.3389\/fncel.2023.1344090. PMID: 38298375; PMCID: PMC10827939.<\/p><\/div>\n<\/div><\/div>\n\n\n

\n\t
\n\t
\n\t
\n\t

Projects<\/h2>

Learn more about our projects.<\/p>Projects<\/a><\/div>\n

\n\t
\n\t<\/figure>\n<\/div>\n<\/div><\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":8,"featured_media":0,"parent":320,"menu_order":1,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_lmt_disableupdate":"no","_lmt_disable":"","inline_featured_image":false,"footnotes":"","fndry_alternate_title":"Alternate Title!"},"class_list":["post-1215","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/www.bcchr.ca\/biochemical-genetics\/wp-json\/wp\/v2\/pages\/1215","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.bcchr.ca\/biochemical-genetics\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.bcchr.ca\/biochemical-genetics\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.bcchr.ca\/biochemical-genetics\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bcchr.ca\/biochemical-genetics\/wp-json\/wp\/v2\/comments?post=1215"}],"version-history":[{"count":3,"href":"https:\/\/www.bcchr.ca\/biochemical-genetics\/wp-json\/wp\/v2\/pages\/1215\/revisions"}],"predecessor-version":[{"id":2015,"href":"https:\/\/www.bcchr.ca\/biochemical-genetics\/wp-json\/wp\/v2\/pages\/1215\/revisions\/2015"}],"up":[{"embeddable":true,"href":"https:\/\/www.bcchr.ca\/biochemical-genetics\/wp-json\/wp\/v2\/pages\/320"}],"wp:attachment":[{"href":"https:\/\/www.bcchr.ca\/biochemical-genetics\/wp-json\/wp\/v2\/media?parent=1215"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}