Open Access Articles- Top Results for Choroideremia


Classification and external resources
ICD-10 H31.2
ICD-9 363.55
OMIM 303100
DiseasesDB 2619
NCI Choroideremia
Patient UK Choroideremia
MeSH D015794

Choroideremia /kɒˌrɔɪdɨˈrmi.ə/ (CHD) is a rare X-linked recessive inherited disorder giving rise to retinal disease and eventual blindness, resulting from degeneration of the choriocapillaris of the choroid and of the retinal pigment epithelium of the retina. The disease results in progressive loss of vision, almost exclusively in males; in childhood, night blindness is the most common first symptom.[not verified in body] As the disease progresses, vision loss results, frequently starting as an irregular ring that gradually expands both in toward central vision and out toward the extreme periphery; progression continues throughout the individual's life, where both the rate of change and the degree of visual loss are variable among those affected, even within the same family.[not verified in body]

The affected tissues include the retinal pigment epithelium (RPE), which is the pigmented cell layer just outside the neurosensory retina that nourishes retinal visual cells;[1][page needed] the RPE overlies the retinal visual cells and is firmly attached to the underlying choroid,[1][page needed] where degeneration of the capillary lamina of choroid (choriocapillaris) is also observed. Photoreceptors of the RPE convert light into the electrical impulses that are transferred to the brain, where the images seen as a result are constructed; the vessels of the choriocapillaris provide oxygen and nutrients to the RPE and photoreceptor cells.[not verified in body] In the early stages of CHD, the choroid and the retinal pigment epithelium begin to deteriorate, after which loss of photoreceptor occurs, leading to loss of vision.[not verified in body] At a molecular level, the root cause of the disease is mutation leading to loss of a specific Rab escort protein 1 (REP1), which, with its partner REP2, are responsible for prenylation of Rab proteins, where the link between the build up of unprenylated Rab proteins and the developing blindness is not yet known.[not verified in body]

Medical approaches to the disease have resulted in the application of a diagnostic test for CHD, and 2014 saw the onset of clinical trials for gene therapies using viral vector-borne RP1 gene constructs aimed at protection of cells not yet lost to the disease. In these early clinical studies, patients have consistently shown improvements during the course of study; persistence data are in the process of being gathered.

Pathophysiology and presentation

Choroideremia is caused by the deletion of the Rab escort protein 1 (REP1). Rab escort protein 2 (REP2) is 75% identical and can to an extent compensate for the loss of REP1.[citation needed] Though the eye does express the REP2 protein (no cell could survive without some REP activity) evidently, in the eye, this is not enough.[citation needed] The REPs are essential for the prenylation of Rab proteins. Studies have shown that there is a build up of unprenylated Rab27 in lymphoblasts from Choroideremia patients. The link between the build up of unprenylated Rab proteins and blindness is not known.[citation needed]

Generally, only males show symptoms of this disease. Initially a person suffering from choroideremia has night blindness, which begins in youth. As the disease progresses, a CHM sufferer loses their peripheral vision and depth perception, eventually losing all sight by middle age. In some cases, a severe loss of acuity and color perception become evident as the disease progresses.


Basic research

Diagnostic testing

There is a genetic blood test to diagnose Choroideremia. It was created by Dr. Ian MacDonald at the University of Alberta. Free genetic testing is available for US and Canadian Residents through the eyeGENE project which is coordinated by the National Eye Institute at the US National Institutes of Health. Human gene therapy trials are underway at the Imperial College of London under the direction of Dr. Miguel Seabra and at Moorfields Eye Hospital in London under the direction of Dr. Robert MacLaren. In the United States preclinical trial work is underway at the University of Pennsylvania under the direction of Dr. Jean Bennett and Dr. Albert Maguire. Dr. Ian MacDonald is also pursuing clinical trials at the University of Alberta in Canada. The Choroideremia Research Foundation, an international non-profit organization that for over ten years has been dedicated to raising awareness and securing funding for choroideremia research, is currently funding pre-clinical trial work for Dr. Seabra and Dr. Bennett. Dr. Ian MacDonald also serves on the board of directors for the CRF and receives funding from CRF-Canada. Human clinical trials are expected to start in the US in 2014. CRF-Canada also supports Dr. Seabra's and Dr. MacLaren's work as does Fight for Sight (UK).


Robert E MacLaren, Professor of Ophthalmology, and investigator at the Nuffield Laboratory of Ophthalmology at the University of Oxford, and colleagues there and at the John Radcliffe Hospital in Oxford have used a gene therapy protocol—first attempted at Moorfields Eye Hospital in London[2]—to attempt to treat the choroideremic REP1 deficiency that leads to degeneration of the choriocapillaris and retinal pigment epithelium and loss of light sensitivity, and eventually, sight.[2][3] The objectives of the protocol, funded by the U.K.'s Health Innovation Challenge Fund were to "assess the safety and tolerability of the AAV.REP1 vector" used to introduce the replacement REP1 gene, through its administration to the retinas of 12 choroideremia patients at 2 doses, and secondarily, to seek to observe therapeutic benefit during the study, and at a 24 month post-treatment time point, based on functional and anatomical tests to evaluate any "slowing down of… retinal degeneration" in treatment versus control groups.[4] The work is an outgrowth of an earlier, promising gene therapy approach to treat Leber congenital amaurosis (LCA),[5] where this effort attempts to introduce new, functioning copies of the REP1 gene to the eye using an adenoviral vector, so to halt cell death associated with this deficiency; the trial gave initial, promising results in January 2014: all of the 6 patients in the treatment group (those receiving the gene replacement) had degeneration to varying degrees before the treatment, and all described vision improvement.[3][2][6][7] Work is underway in this trial to determine the persistence of the therapeutic improvements that were initially observed.

Celebrities afflicted

A number of individuals in very visible public roles are afflicted, and some have been involved in fundraising efforts for the disease. The former UK Labour Member of Parliament Siôn Simon is a known sufferer.[citation needed] Comic and activist E.J. Scott, partner of Deborah Ann Woll is also fighting the disease, and is involved in regular fundraising efforts.[8][9]

Further reading

  • Danny Boren, 2015, "First U.S. Gene Therapy Clinical Trial to treat Choroideremia initiated in Philadelphia," Choroideremia Research Foundation (online), Press Release Summary, January 20, 2015, see [10], accessed 23 April 2015.
  • Cory MacDonald, 2015, "Nightstar Receives U.S. and European Orphan Drug Designation for Gene Therapy to Treat Choroideremia," Choroideremia Research Foundation (online), Press Release Summary, March 24, 2015 (release date, January 11), see [11], accessed 23 April 2015.
  • FFB, 2015, "U.S. Human Study for Choroideremia Gene Therapy Launched by Spark Therapeutics," Foundation Fighting Blindness (online), January 27, 2015, see [12], accessed 23 April 2015.
  • NLO, 2014, "First Results of Choroideremia Gene Therapy Trial (2014)," Nuffield Laboratory of Ophthalmology (online), Press Release, undated, see [13], accessed 23 April 2015.


  1. ^ a b B. Cassin & S. Solomon (2001). Dictionary of eye terminology. Gainesville, FL: Triad Pub. Co. pp. TBD. ISBN 0-937404-63-2. [page needed]
  2. ^ a b c Pallab Ghosh, 2011, "Health: Gene therapy used in a bid to save a man's sight," at BBC News (online), October 27, 2011, see [1], accessed 23 April 2015.
  3. ^ a b Abigail Beall, 2014, "Gene therapy restores sight in people with eye disease," New Scientist (online), January 16, 2014, see [2], accessed 23 April 2015.
  4. ^, 2014, "Gene Therapy for Blindness Caused by Choroideremia (Sponsor:University of Oxford): NCT01461213," at, see [3], accessed 23 April 2015.
  5. ^ Ewen Callaway, 2008, "Gene therapy success 'reverses' blindness," New Scientist (online), April 28, 2008, see [4] and [5] and [6], accessed 23 April 2015.
  6. ^ Hendrik P. N. Schollemail & José A Sahel, 2014, "Comment: Gene therapy arrives at the macula," Lancet, 383:1105 (March 29, 2014; online, January 16), DOI 10.1016/S0140-6736(14)60033-7, see [7], accessed 23 April 2015.
  7. ^ MacLaren, R. E.; Groppe, M.; Barnard, A. R.; Cottriall, C. L.; Tolmachova, T.; Seymour, L.; Clark, K. R.; During, M. J.; Cremers, F. P. M.; Black, G. C. M.; Lotery, A. J.; Downes, S. M.; Webster, A. R.; Seabra, M. C. (2014). "Retinal gene therapy in patients with choroideremia: Initial findings from a phase 1/2 clinical trial". The Lancet 383 (9923): 1129–37. PMID 24439297. doi:10.1016/S0140-6736(13)62117-0. 
  8. ^ Bill Dwyre, 2013, "Though going blind, E.J. Scott keeps looking ahead, moving forward," L.A. Times (online), January 11, 2013, see [8], accessed 23 April 2015.
  9. ^ E.J. Scott, 2015, "This is my 40: Running 7 continents in 1 year, blindfolded," at Crowdrise (online crowdsourcing), undated, see [9], accessed 23 April 2015.

External links

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