• Obscure Dietary Supplement Overcomes Genetically Inherited Form Of Eye Disease

    Posted July 27, 2011: by Bill Sardi

    San Dimas, CA (July 26, 2011)- Idebenone gets the headlines today for restoring vision to patients with an otherwise incurable inherited eye disease — Leber’s heredity optic neuropathy. And this discovery suggests idebenone may be helpful for patients with glaucoma, another optic nerve disease.

    You may not be familiar with idebenone, produced by a pharmaceutical company in Japan. But you may have heard about idebenone under another name – coenzyme Q10. Idebenone is known as synthetic analog of coenzyme Q10, a natural antioxidant produced in the body. To be sold as a patentable drug in Japan the molecule had to be re-arranged molecularly.

    Actually, idebenone has been in human clinical use since the 1980s and also sold as a nutritional supplement in the U.S. Oddly, the U.S. Food & Drug Administration allows certain safe synthetic derivatives of naturally occurring molecules like coenzyme Q10 to be marketed as dietary supplements. That may soon change with issuance of newly proposed guidelines by the FDA recently.

    The big news is that an inherited disease can be remedied, at least in part, by a natural molecule. Inherited gene mutations may not result in inevitable disease, in this instance, loss of sight! That should have been front-page news across the globe. The story is revealed at ScienceDaily.com today.

    The disease causes a decline in coenzyme Q10 production within the mitochondria, the energy-producing compartments in living cells.

    An odd part of this story is that it is not the first time this discovery has been reported. Researchers in Taiwan first reported the successful treatment of a child with Leber’s Hereditary Optic Neuropathy in 2003 with coenzyme Q10. Why it has taken eight more years to complete a clinical trial goes unexplained. Another similar case involving inherited diabetes and hearing loss successfully treated with coenzyme Q10 was reported in 2008.

    It has recently been found that coenzyme Q10 levels can decline by as much as 40% in the aged retina of the human eye. This may mean coenzyme Q10 may be an unappreciated remedy for glaucoma (optic nerve) and macular degeneration (central retina).

    There are few if any studies that compare idebenone with coenzyme Q10, but make sure they both serve the same biological purpose – to invigorate and restore coenzyme Q10 to healthy and youthful levels when taken as a dietary supplement.

    Researchers in Italy proposed coenzyme Q10 could be used therapeutically for glaucoma in 2007. Two years earlier researchers in Italy successfully used coenzyme Q10 combined with acetyl-L-carnitine and omega-3 oils to successfully treat human cases of macular degeneration. While this combination of supplements might be difficult for senior Americans on a limited income to purchase, eye doctors say there is no effective treatment for the vast majority of patients stricken with this age-related eye disease. After 12 months on this nutrient combination, only 1 of 48 (2%) patients suffered a decline in vision whereas 9 of 53 (17%) patients given an inactive placebo pill experience visual decline. That is almost a 9-fold difference. Few patients with macular degeneration are ever informed of this study. #### © 2011 Bill Sardi, Knowledge of Health, Inc. July 26, 2011


    Web address: http://www.sciencedaily.com/releases/2011/07/110725202243.htm

    Drug Shown to Improve Sight for Patients With Inherited Blindness

    In some severely affected patients such as those who were unable to read any letters on the eye chart, the treatment with idebenone resulted in a marked improvement in their vision. In nine patients (12 eyes) out of 36 patients (61 eyes) taking idebenone, vision improved to the extent that patients were able to read at least one row of letters on the chart. (Credit: © Matthew Benoit / Fotolia)

    ScienceDaily (July 25, 2011) — A clinical trial led by Newcastle University shows that the drug, idebenone (Catena®), improved the vision and perception of colour in patients with Leber’s Hereditary Optic Neuropathy (LHON). The inherited condition means patients, who can see normally, lose the sight in one eye then within 3 to 6 months lose the sight in their other eye.

    In some severely affected patients such as those who were unable to read any letters on the chart, the treatment with idebenone resulted in a marked improvement in their vision. In nine patients (12 eyes) out of 36 patients (61 eyes) taking idebenone, vision improved to the extent that patients were able to read at least one row of letters on the chart. In contrast not a single patient of the 26 who were taking the placebo improved to that extent.

    Inherited from the mother, and mainly affecting men, LHON is caused by damage to the mitochondria in the eyes — the ‘batteries’ which power their cells. It is one of the most common causes of inherited blindness and is thought to affect around 2,000 people in the UK, around 10,000 in Europe and a further 10,000 in the USA.

    “This is the first proven treatment for a mitochondrial disorder. We have seen patients who couldn’t even see an eye chart on the wall go on to read the first line down — and some even attempted the second line. For these patients, it can mean a vast improvement in their quality of life,” said Professor Patrick Chinnery, a Wellcome Trust Senior Fellow in Clinical Science at Newcastle University who also works at the Royal Victoria Infirmary in Newcastle — part of the Newcastle upon Tyne Hospitals NHS Foundation Trust.

    Released July 25 in the journal Brain, the authors describe how patients with LHON were recruited from Newcastle Hospitals in the UK, in Munich, Germany and in Montreal, Canada for a double blind trial. Patients were either given idebenone for 24 weeks or a placebo.

    At the end of the six months, some patients who were taking idebenone had improved vision and this is the first time a successful treatment has been found. The greatest improvement was seen in patients who had deteriorated in one eye more than the other.

    Professor Chinnery explained: “We saw most progress in people who had better vision in one eye than the other — this tends to indicate that they are at an earlier stage of the condition. While we know that their vision is not what it once was, we also know that this treatment can dramatically improve their lives — some were able to move around more easily or even see family photos again.”

    Idebenone penetrates into the mitochondria and is thought to mop-up toxic free radicals and enhance mitochondrial function. Previous research had provided anecdotal reports of improvements in vision but this is the first time it had been put to the test in a clinical trial. The drug company which sponsored this trial, Santhera Pharmaceuticals, is now seeking marketing approval from the European Medicines Agency for it to be offered as a standard form of treatment.

    “We are hearing from patients that they still have improved vision — even though they are no longer taking the drug but we would like to verify this and study the effect further,” said Professor Chinnery. “There may also be a case for offering idebenone from the first moment that LHON is diagnosed — preferably before any symptoms are shown — and a further trial would ideally examine this.”

    “I lost the sight in my left eye in just five days”

    Mike Scholes, 58 from Lindfield in West Sussex, UK and a graduate of Newcastle University took part in the trial. He said: “I was training for a freefall parachute jump five years ago when I noticed I was having problems with my eye. I went for an eye test at the optician and on the way to pick up my glasses five days later, I nearly crashed the car. The optician tested my right eye and there was no problem, when he came to the left eye I asked him to switch on the machine — and he said he already had. I had lost the sight in my left eye in just five days.

    “This meant an abrupt change in my life — I had a very successful hot air balloon business and I had to stop flying. I had to sell my cars as I could no longer drive.

    “Following seven months of tests including CAT scans, X-Rays, MRI scans and a lumbar puncture, I was finally given a DNA test which revealed I had Leber’s hereditary optic neuropathy.

    “It was around this time that my vision started to go in my second eye. I couldn’t see in an increasingly large area in the centre of my eyes and gradually colours disappeared. At worst the only colours I could make out were shades of blue.

    “Soon after friends spotted a clinical trial in Newcastle, I volunteered to take part and started taking the tablets three times a day — not knowing whether I was taking a placebo or the drug.

    “After just a month and a half I noticed that the area affected in the centre of my vision was smaller. The improvement continued and I began to appreciate colours again seeing yellow and most reds.

    “Having Leber’s hasn’t stopped me enjoying life to the full — I run marathons with a guide, I’ve hiked to the North pole — but the noticeable improvement in my vision means daily life is easier. I can use a computerised viewer to help me read, I can get dressed without having to use a detector for the colours of clothes and while initially I couldn’t even see the eye chart, now if I get really close to a street sign I can read it.”

    Story Source:

    The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Newcastle University, via EurekAlert!, a service of AAAS.

    Journal Reference:

    1. Thomas Klopstock, Patrick Yu-Wai-Man, Konstantinos Dimitriadis, Jacinthe Rouleau, Suzette Heck, Maura Bailie, Alaa Atawan, Sandip Chattopadhyay, Marion Schubert, Aylin Garip, Marcus Kernt, Diana Petraki, Christian Rummey, Mika Leinonen, Günther Metz, Philip G. Griffiths, Thomas Meier, and Patrick F. Chinnery. A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy. Brain, July 25, 2011 DOI: 10.1093/brain/awr170

    Brain (2011) doi: 10.1093/brain/awr170 First published online: July 25, 2011

    A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy

    1. Thomas Klopstock1, Patrick Yu-Wai-Man2,3,4, Konstantinos Dimitriadis1,
    2. Jacinthe Rouleau5, Suzette Heck1, Maura Bailie2,3,4, Alaa Atawan2,3,4,
    3. Sandip Chattopadhyay2,3,4, Marion Schubert1, Aylin Garip6, Marcus Kernt6,
    4. Diana Petraki7, Christian Rummey7, Mika Leinonen8, Günther Metz7,
    5. Philip G. Griffiths2,3,4, Thomas Meier7 and Patrick F. Chinnery2,3,4

    + Author Affiliations

    1. Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich, Germany
    2. Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne Foundation Hospital, NE1 4LP, NHS Trust, UK
    3. Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne Foundation Hospital, NE1 4LP NHS Trust, UK
    4. Mitochondrial Research Group, Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK
    5. Ophthalmology Department, Centre Hospitalier de l’Université de Montréal (CHUM), Montreal, Quebec H2L 4M1, Canada
    6. Department of Ophthalmology, Ludwig-Maximilians-University, Munich, 80336 Germany
    7. Santhera Pharmaceuticals, 4410 Liestal, Switzerland
    8. Pharma, Stockholm, 16440 Kista, Sweden
    1. Correspondence to: Patrick F. Chinnery, Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK E-mail: p.f.chinnery@newcastle.ac.uk
    2. Correspondence may also be addressed to: Thomas Klopstock, Dept. of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich, Germany E-mail: thomas.klopstock@med.uni-muenchen.de


    Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber’s hereditary optic neuropathy is the most common mitochondrial DNA disorder causing irreversible blindness in young adult life. Anecdotal reports support the use of idebenone in Leber’s hereditary optic neuropathy, but this has not been evaluated in a randomized controlled trial. We conducted a 24-week multi-centre double-blind, randomized, placebo-controlled trial in 85 patients with Leber’s hereditary optic neuropathy due to m.3460G>A, m.11778G>A, and m.14484T>C or mitochondrial DNA mutations. The active drug was idebenone 900 mg/day. The primary end-point was the best recovery in visual acuity. The main secondary end-point was the change in best visual acuity. Other secondary end-points were changes in visual acuity of the best eye at baseline and changes in visual acuity for both eyes in each patient. Colour-contrast sensitivity and retinal nerve fibre layer thickness were measured in subgroups. Idebenone was safe and well tolerated. The primary end-point did not reach statistical significance in the intention to treat population. However, post hoc interaction analysis showed a different response to idebenone in patients with discordant visual acuities at baseline; in these patients, all secondary end-points were significantly different between the idebenone and placebo groups. This first randomized controlled trial in the mitochondrial disorder, Leber’s hereditary optic neuropathy, provides evidence that patients with discordant visual acuities are the most likely to benefit from idebenone treatment, which is safe and well tolerated.

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