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A Gene Therapy Clinical Trial for Achromatopsia

By Prateek Buch, on 25 March 2013

We are pleased to have been awarded a major research grant from the Medical Research Council (MRC), to develop gene therapy for achromatopsia. Affecting around  1/30000 people, achromatopsia is an inherited condition that causes the complete absence of colour vision from birth, a severe reduction in central visual acuity, extreme sensitivity to light and significant impairment of daylight vision from an early age.

Roughly half of all achromatopsia cases in the UK are associated with damage to the CNGB3 gene – the 4 other genes associated with the disease are much rarer, making the CNGB3 form of the condition amenable to treatment.

We will use the funding (£2.1 million) over the next five years to produce and test an engineered viral vector suitable for use in the clinic, and conduct a Phase I/II clinical trial of gene therapy in patients with achromatopsia caused by defects in the CNGB3 gene.

In laboratory models, CNGB3 gene replacement using AAV is one of the most effective therapies being developed for sight loss caused by defects in the light-sensitive photoreceptor cells of the retina. In a study published in the journal Human Molecular Genetics we showed that gene delivery using an engineered adeno-associated virus (AAV) can restore vision in a model of achromatopsia lacking CNGB3. Our study showed long-term restoration of sight as measured by improvements in the ability of treated mice to track a visual stimulus. Dogs with a similar defect have been treated using AAV gene therapy by a group in the United States.

As well as the MRC funding for the trial, we have secured ethical approval for the study from the National Research Ethics Committee (NRES). We will soon begin production and safety testing of the clinical grade virus to be used in the clinic, after which we can seek full regulatory approval from the Medicines and Healthcare products Regulatory Agency (MHRA) to begin the trial.

We plan to use a different sub-type of AAV than in our previous gene therapy trial aimed at the RPE65 form of Leber congenital amaurosis (LCA). This sub-type has been shown to be more effective at delivering genes to the light-sensitive photoreceptors of the retina than the sub-type used in our previous gene therapy trial, which targeted a defect in the retinal pigment epithelium (RPE).

Commenting on the prospect of a new trial for achromatopsia, Professor Robin Ali said: “This funding from the MRC is crucial for our programme. It will help us demonstrate that gene therapy can be used to treat photoreceptor cell defects, having shown it can be safe and effective in treating RPE defects.”

We will provide further updates on progress towards a clinical trial for achromatopsia both here and on our website.

30 Responses to “A Gene Therapy Clinical Trial for Achromatopsia”

  • 1
    Rick van Loy wrote on 25 March 2013:

    This is great news i am waiting for fourthy-four years now.

  • 2
    Cheryl Evans wrote on 2 May 2013:

    Well, I never thought I would be hoping to be suffering from a CNGB3 mutation rather than one of the less common ones. I certainly wouldn’t mind being in the majority if it could help to get my vision fixed.

  • 3
    EyeTherapy wrote on 2 May 2013:

    Thanks for the comments!

    Rick, we are glad to be making some progress and will keep everyone up-to-date.

    Cheryl, I understand your point! We have to choose the forms of sight loss that we treat very carefully, and part of that choice involves looking at the numbers of people that form affects. It is likely that the technology being tested here – the use of viral vectors to deliver genes – will accelerate the development of similar therapies for related forms of achromatopsia and other sight loss conditions. If you don’t mind, I’ll email later!

    Thanks

  • 4
    Liyaquat Lashkariya wrote on 18 May 2013:

    How does this work for people older than 25-30? In the canine testing it worked better for the younger dogs. Either way I’m glad to hear this amazing news and that there is hope for people like us.

  • 5
    EyeTherapy wrote on 20 May 2013:

    Hi Liyaquat, thanks for the excellent question! The answer is that we do not know, which is part of the reason we need to do a clinical trial. As you rightly point out, in dogs the gene therapy did worked better for younger animals – although it is worth noting that even the dogs in the “young” group had severely reduced daytime vision at the time they were treated. This suggests that achromatopsia may be treatable amongst people with established disease. Results from our study in mice shows that some measures of visual function can be improved when treatment is given at older ages, but that the best improvement in vision is when the mice were younger.
    As I say, answering this question about whether the treatment can work for older patients is an important part of our trial, which is why we plan to include patients from a range of ages. I recommend that you email eye.info@ucl.ac.uk if you have any further questions!

  • 6
    Nina Konvalinka wrote on 20 May 2013:

    That’s excellent news!
    Is there a way for people interested in participating in this clinical trial to get in touch with you and is it limited only to UK citizens? I’m 23 years old student from Slovenia with a CNGB3 gene mutation (I finally got the results back from Casey Eye Institute in Oregon just a couple of days ago).
    Regards,
    Nina

  • 7
    EyeTherapy wrote on 20 May 2013:

    Hi Nina, thanks for the question!

    I recommend that you email eye.info@ucl.ac.uk so that we can discuss the trial and how we decide who can participate.

    Many thanks!

  • 8
    Nina Konvalinka wrote on 20 May 2013:

    Thank you. Email sent 🙂
    Regards,
    Nina

  • 9
    Nazia Khalid wrote on 20 May 2013:

    Hi: Its a great news for a parent like me who would open internet everyday with lots of prayers and good wishes for my children and many other having achromatopsia.My kids are 9 and 4 yrs old. I wish that soon this treatment will be open for all without any side effects. Time only has the answers of all the questions.Wishing Best of Luck for the team of doctors working on it and best of luck to patients and their families.

  • 10
    J.Deschaine wrote on 24 May 2013:

    Great news all around. As far as the older eyes question a new article from Michigan State University published in Molecular Therapy may hold some promise. See Transient Photoreceptor Deconstruction by CNTF Enhances rAAV-Mediated Cone Functional Rescue in Late Stage CNGB3-Achromatopsia April 9 2013.

  • 11
    Prateek Buch wrote on 24 May 2013:

    Hi Jake – thanks for drawing our attention to that study, had see data from this presented at conference before but wasn’t aware it had been published! Cheers! It does look as though combining a small, transient dose of CNTF with gene therapy does allow older dogs to benefit from gene replacement. A note of caution that I am sure you appreciate – given that this study is in dogs with CNGB3 mutations, it is hard to say what effect the addition of CNTF would have in humans. It is known that long-term exposure to CNTF, when delivered by, say, a gene therapy vector, damages photoreceptors and causes a loss of visual function, in animals. Clinical trials using devices that secrete CNTF have provided mixed results so far, so it remains to be seen whether the encouraging results in the CNGB3 dog study can be replicated in humans. Worth looking out for though, so watch this space! thanks again for the comment

  • 12
    Marilyn F wrote on 24 May 2013:

    Great news. I just found out that my achromatopsia is caused by the CNGB3 gene. I hope the trial goes well!!!

  • 13
    Eye_Therapy wrote on 24 May 2013:

    Hi Marylin – thanks for the comment, we will of course keep you and everyone else posted through the website, if you have any further questions please don’t hesitate to email eye.info@ucl.ac.uk – thanks!

  • 14
    alley wrote on 6 June 2013:

    My daughter is 8 years old can she be cured

  • 15
    Eye_Therapy wrote on 6 June 2013:

    Hi Alley – thanks for the question. It is too early to use the phrase cure, but it may be possible to participate in some of the studies we are conducting, including the clinical trial. However, as there are strict criteria for being eligible for the trial, I recommend that you email eye.info@ucl.ac.uk and we can discuss it! thanks

  • 16
    IVO RATINI wrote on 22 August 2013:

    sono un’acromata

  • 17
    IVO RATINI wrote on 22 August 2013:

    Sono molto interessato ai vostri studi perchè mi hanno sempre spiegato che per l’acromatopsia non vi erano speranze di soluzione, sono acromata dalla nascita e ora grazie ad un’amico sono riuscito ad avere vostre notizie, vivo in italia a bologna, e presto farò una mappatura genetica per capire se appartengo CNGB3, grazie

  • 18
    Prateek Buch wrote on 22 August 2013:

    Grazie mille per la tua inchiesta! Capisco solo un poco d’italiano, ma posso inviare un email con piu informazioni!

  • 19
    stefania personè wrote on 20 September 2013:

    ho appreso la notizia con grande gioia e paura allo stesso tempo….dopo 42 anni , lo studio, il lavoro , i sacrifici , una bella famiglia con 3 figlie stupende e la consapevolezza che non sarei mai guarita…..è difficile accettare pure le cose positive……ma voglio vedere gli uccellini volare…….presto manderò la meil…..buon lavoro e GRAZIE DI ESISTERE

  • 20
    Gelateria Desideria wrote on 20 September 2013:

    sono Stefania 42 anni e tre bimbe sane……sono molto felice per la notizia ma anche spaventata….manderò la mail per partecipare alla ricerca se vorrete…….ho fatto il test e la mutazione è sul gene CNGB3…..buon lavoro e GRAZIE DI ESISTERE

  • 21
    Gelateria Desideria wrote on 20 September 2013:

    dovete scusare il doppio commento non avevo capito che il primo a mio nome era andato a buon fine ….stefania personè e gelateria desideria sono la stessa persona …..IO…..ma come ben sapete ci vedo davvero poco e già che uso il computer è un miracolo

  • 22
    Antoine wrote on 15 October 2013:

    This is fantastic news. Our 8 year old son has achromatopsia. We are very hopefull that these tests may result in gene therapy for our son.

  • 23
    Dagmar Jeurissen wrote on 30 October 2013:

    I have a son aged 8 suffering from achromatopsia, is it possible that he will be included in the trials? He has a defect on gene CNGB3 (as established by the Dutch Institute of Neuroscience).

  • 24
    Bramaramba S wrote on 4 February 2014:

    Great news we are waiting for this to happen

  • 25
    Bharat Mankad wrote on 20 August 2014:

    I read your article on achromatopsia condition, which is very inspirational for me, as I have similar condition and happy to participate in research. Prof Webster at Moorefild found matched gene and he said Jonathan will contact me for testin.

    Thank you in advance, and I await to hear more information on thisc condition.

    Bharat Mankad

  • 26
    Read %url_domain% wrote on 17 October 2014:

    It¡¦s really a great and helpful piece of information. I¡¦m satisfied that you shared this helpful information with us. Please keep us informed like this. Thank you for sharing.

  • 27
    Samme wrote on 4 November 2014:

    This advance by Andaloussi et al could also be really good:
    http://www.ncbi.nlm.nih.gov/pubmed/23154783

  • 28
    Andi M Skilton wrote on 4 November 2014:

    Hi Samme – whilst a very interesting new technological development I am afraid that in the case of the CNGB3 mutation in achromatopsia, it is unlikely that this approach would be of benefit. SiRNA technology can be used to silence or deactivate genes that produce harmful products. However, in the case of the CNGB3 mutation, these products are thought not to be harmful they just do not work. Therefore, it is unlikely that deactivating the gene will have any additional benefits and in this instance using gene therapy to replace CNGB3 is still thought to be a more appropriate approach.

  • 29
    Jennifer mccormick wrote on 21 June 2015:

    I have a no chromatography I have had my daughter mapped . Morefiels in London hold the I’m formation on me. I am so excited about the prospect of human trial. It would be life changing to be able to be in the sun etc. . Please concise me for the trial PLEASE.

  • 30
    Andi M Skilton wrote on 25 June 2015:

    Dear Jennifer
    Thank you for your interest in this research. As a patient at Moorfields should there be an appropriate opportunity for you to participate in any relevant research someone will be in contact. More information on how Moorfields patients may get involved with research can be found as this link:
    http://www.moorfields.nhs.uk/sites/default/files/Consent%20for%20Contact%20FAQs.pdf

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