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Gene therapy for eye diseases in 2014

Gene therapy for eye diseases in 2014

Publish date: 2015-02-01

By David Gamero Ledo, Elżbieta Świętek & Klaudia Polakowska, Centre for Innovation, Technology Transfer and University Development, Jagiellonian University

Tags: gene therapy , eye diseases , eye conditions

Introduction

In 2013, R&D related to eye conditions were the most attractive to venture capitals (VC). Theysupported this research area with$0.86billion.Other importantmedical sectors for VC’s were endocrine glands and pancreas ($0.73 billion), research on brain ($0.66 billion) and research on heart ($0.66 billion). Also more fundswere spent in the eye-related research than any other part of the body in the first quarter of 2014($0.71 billion). A total of 36 deals were signedin the mentioned period (the average value was $20 million per contract which was surpassed only by contracts for endocrine glands and pancreas, skin and urinary systems).

Regarding investments in gene therapy, due to the advances in this field, venture capitals have invested more dollars since 2010 than they had invested in last decade. Research in the brain and blood-related gene therapy were the favourite one for the investors until the first half of 2014. The third position in this rank was for gene therapy for eye diseases. That is why gene therapy for eye diseases represents a recent field which will most likely be very important in next years.

Why gene therapy for eye diseases?

Gene therapy is defined as an experimental technique that uses the delivery of genetic material to treat or prevent diseases by (a) delivering a working copy of a damaged gene that causes diseases; (b) inactivating a mutated gene that is functioning improperly; or (c) introducing a new gene into the body to help fight diseases.

However, most gene therapies which are currently closer to clinical use have some of the following factors in common:

  • Their objective is to correct single-gene defects or disorders by adding a gene for a functional protein.
  • They aim to transform cells which are easily accessible, usually having some degree of immune privilege.
  • They only need to have effects on a relatively small number of cells in order to be successful.

Total or partial visual loss may be caused by many reasons such as accidents or injuries to the eye surface, diabetes or macular degeneration. Sometimes it occurs because of heredity. Severalinherited causes of blindness meet abovementioned requirments to be the target of a gene therapy. For instance, one of the form of inherited vision loss is called Leber’s Congenital Amaurosis (LCA) orchoroideremia. Both of these disorders are caused by a mutation in one single gene and affect to eye cells.

The case of Leber’s Congenital Amaurosis (LCA)

Leber’s Congenital Amaurosis (LCA) is an eye disorder consisting in a severe dystrophy of the retina. This inherited eye disease,which is one of the most common causes of blindness in children, can be detected in the first year of life and occurs in 2 to 3 per 100,000 newborns. Mutations in the CEP290, GUCY2D and RPE65 genes are the most frequent causes of the LCA.

The first gene therapy in an animal model of retinal dystrophy using an adeno-associated virus (AAV) was done in a dog which had a mutation in the RPE65 gene. The success of the studies showed that it was an ideal candidate to develop a gene therapy for humans.

In 2007 the first LCA patients were treated with gene therapy, receiving working RPE65 genes. Theresults of three independent clinical trials for retinal pigment epithelium-specific 65 kDa protein (RPE65) deficiency were published the following year. The results of several clinical trials, some of which are still ongoing, are encouraging. It is very likely that the gene therapy product for Leber’s Congenital Amaurosis will be the first, approved by the FDA.

The case of Choroideremia

Choroideremia (CHM) is a retinal degenerative disease whose symptoms evolve from night blindness to peripheral visual field loss. It is an X-linked recessive disease so it mainly affects males, with an estimated prevalence of 1 in 50,000 people. The cause of the disease is a mutation in a gene called CHM, which encodes Rab escort protein 1 (REP1).

In January 2014, Prof Robert MacLaren (University of Oxford) and colleagues published early results and initial findings from I/II phase of clinical trial. They try to assess the effects of retinal gene therapy with an adeno-associated viral (AVV) vector encoding REP1 in six patients ages 35 to 63.Although the researchers only aimed to carry out the treatment without causing damage to the eye, results were better than they expected. Six months after the operation,they observed an increase in the point of maximal sensitivity in all treated eyes as well as improvement of mean retinal sensitivity in five treated eyes.

The researchers pointed that using gene therapy at earlier stage could save even more light-sensing cells in retina. When retinal damage gets to a certain point it is impossible to repair it. They propose to apply the gene therapy before vision is gone.

Besides, choroideremia presents a pattern of neurodegeneration which representsmuch larger group of photoreceptor degenerative disorders, such as Age-related Macular Degeneration (AMD) and retinitis pigmentosa. For that reason the study is promising not only for the treatment of choroideremia but also for potential treatments in order to prevent from blindness in other retinal diseases.

Gene therapies on the market

The 90’s was a bad decade for gene therapy. To sum up, almost 4000 patients were treated with gene therapy and almost no success was reported. To make matter worse, several cases of cancer were attributed to gene therapy. In 1999 died a man that had been undergoing gene therapy. Despite all, in 2003 China became the first country that approved the commercial production of a gene therapy. For many, the approval of the therapy commercialized under the brand name of Gendicinewas a success.It opened the door to investors confidence and development of new therapies.

In November 2012the European Medicines Agency (EMA) approved the first in the western world (including Europe and USA)gene therapy,Glybera. The product was puton marketfor the first time in Germany inNovember 2014. It treats a rare, inherited disease in which patients cannot metabolize fat in the blood. The treatment price per patientreaches €1.1 million.

Thanks to investments and conducted research, several new gene therapies have a chance to be approved. They maybe utilizedin the field of oncology or ophthalmology. They also may be related to haemophilia or infectious diseases.

At least twenty ongoing clinical trials registered in ClinicalTrials.govare related to gene therapy for eye diseases, including, inter alia, Leber’s Congenital Amaurosis (LCA), Leber’s Hereditary Optic Neuropathy (LHON), choroideremia and Wet AMD. According to The Journal of Gene Medicine, there are thirty-three gene therapy clinical trials related to ocular diseases. It is only the 1.6% of all gene therapy clinical trials but some of these therapies are close to be approved. The leader is Spark Therapeutics which has a gene therapy in Phase III for patient with LCA. Results will be ready in the second half of 2015. Other companies, especially Oxford BioMedica and Sanofi, are also close to the approval for the first gene therapy for eye diseases. In fact, bothcompanies are collaborating to develop two products for the treatment of ocular diseases.

To sum up, gene therapies for eye diseases have made a great progress in 2014 andfurther success cases are likely in 2015. What's more, further successful results of clinical trials will attract more investment and will promote the development of new gene therapies.

References

Arons I. (January 17, 2013 - updated October 27, 2014). Irv Arons’ Journal [InternetBlog]. Retrieved from: http://irvaronsjournal.blogspot.com/2013_01_01_archive.html

Carvalho, L. S., &Vandenberghe, L. H. (2014). Promising and delivering gene therapies for vision loss. Vision Research. http://dx.doi.org/10.1016/j.visres.2014.07.013

DeWeerdt, Sarah. (October 6, 2014). Gene therapy: a treatment coming of age. The Pharmaceutical Journal. Retrieved from: http://www.pharmaceutical-journal.com/news-and-analysis/feature/gene-therapy-a-treatment-coming-of-age/20066677.article

Gene Therapy Clinical Trials Worldwide. (Updated June 2014). The Journal of Gene Medicine, © John Wiley and Sons Ltd. Retrieved from: http://www.abedia.com/wiley/indications.php

Gomley, Brian. (September 14, 2014). Gene Therapies Push Investors to Examine New Areas of Human Body. Wall Street Journal. Retrieved from: http://blogs.wsj.com/venturecapital/2014/09/14/gene-therapies-push-investors-to-examine-new-areas-of-human-body/

MacDonald IM, Smaoui N, Seabra MC. Choroideremia. 2003 Feb 21 [Updated 2010 Jun 3]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1337/

MacLaren, R. E., Groppe, M., Barnard, A. R., Cottriall, C. L., Tolmachova, T., Seymour, L., et al. (2014). Retinal gene therapy in patients with choroideremia: Initial findings from a phase 1/2 clinical trial. Lancet, 383, 1129–1137. http://dx.doi.org/10.1016/S0140-6736(13)62117-0

Weleber RG, Francis PJ, Trzupek KM, et al. Leber Congenital Amaurosis. 2004 Jul 7 [Updated 2013 May 2]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.Available from:http://www.ncbi.nlm.nih.gov/books/NBK1298/

Young Rojahn, Sarah. (January 16, 2014). Gene Therapy Tested as a Way to Stop Blindness. MIT Technology Review. Retrieved from: http://www.technologyreview.com/news/519426/gene-therapy-tested-as-a-way-to-stop-blindness/

Young Rojahn, Sarah. (September 30, 2013). When Will Gene Therapy Come to the U.S.?. Retrieved from:http://www.technologyreview.com/news/519071/when-will-gene-therapy-come-to-the-us/

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2016-04-03 02:53:10 +0200
'After being in relationship with Wilson for seven years,he broke up with me, I did everything possible to bring him back but all was in vain, I wanted him back so much because of the love I have for him, I begged him with everything, I made promises but he refused. I explained my problem to someone online and she suggested that I should contact a spell caster that could help me cast a spell to bring him back but I am the type that don't believed in spell, I had no choice than to try it, I meant a spell caster called Dr Zuma zuk and I email him, and he told me there was no problem that everything will be okay before three days, that my ex will return to me before three days, he cast the spell and surprisingly in the second day, it was around 4pm. My ex called me, I was so surprised, I answered the call and all he said was that he was so sorry for everything that happened, that he wanted me to return to him, that he loves me so much. I was so happy and went to him, that was how we started living together happily again. Since then, I have made promise that anybody I know that have a relationship problem, I would be of help to such person by referring him or her to the only real and powerful spell caster who helped me with my own problem and who is different from all the fake ones out there. Anybody could need the help of the spell caster, his email: spiritualherbalisthealing@gmail.com or call him +2349055637784 you can email him if you need his assistance in your relationship or anything. CONTACT HIM NOW FOR SOLUTION TO ALL YOUR PROBLEMS'
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