Opið bréf til íslenskra augnlækna - Mikilvægi snemmtækra greininga á arfgengum augnsjúkdómum eykst

Flestir þeirra sem verða blindir eða alvarlega sjónskertir á unga aldri eða snemma á fullorðinsárum verða það sökum arfgengra hrörnunarsjúkdóma í sjónhimnunni (RP og tengdir sjúkdómar). Engar meðferðir eru til við þessum augnsjúkdómum í dag og því er það hlutskipti þeirra sem eru með þessa sjúkdóma að tapa sífellt meiri sjón með árunum og getur sjónmissirinn endað í alblindu. Mjög misjafnt er hversu hratt þessir sjónhimnusjúkdómar þróast, allt frá árum yfir í áratugi, og því er það mjög einstaklingsbundið hvenær og hverjir verða blindir, sumir á unglingsárum og aðrir seinna á fullorðinsárum. Algengt er að snemma í hrörnunarferlinu séu þessi sjúkdómar ekki vel greinanlegir nema sérstaklega sé skimað eftir þeim. Þannig getur einstaklingur með tiltekna birtingarmynd af slíkum sjúkdómi, sem gæti lýst sér í einungis 1/10 af fullu sjónsviði, náttblindu en skarpri og mjög þröngri miðjusjón, staðist almennt sjónskerpupróf (lesa á stafaspjaldið) sem oft eru lögð fyrir einstaklinga vegna endurnýjunar á ökuskírteini. Viðkomandi einstaklingur er hins vegar lögblindur.

Verðmæti sjónar
Dæmi er um það, bæði hérlendis og erlendis, að einstaklingar sem eru með þessa arfgengu hrörnunarsjúkdóma í sjónhimnu hafa ýmist verið að fá enga greiningu, ranga greiningu eða greiningu sem kemur mjög seint í sjúkdómsferlinu, jafnvel þegar fólk er orðið lögblint.

Blindrafélagið hefur í tvígang látið Capacent Gallup gera fyrir sig skoðanakannanir meðal almennings, 2009 og 2011, þar sem spurt er: Hvað af  tilteknum heilsufaráföllum fólk telji að myndi hafa neikvæðustu áhrif á lífsgæði sín. Aðeins lömun skoraði hærra í svörun heldur en sjónmissir. Þar fyrir neðan voru áföll eins og hjartaáfall, heilablóðfall, krabbamein og önnur áföll sem auðveldlega geta dregið fólk til dauða. Úr þessu má lesa ákveðið verðmætamat og um leið þá miklu angist sem fólk stendur frammi fyrir gagnvart því að missa sjónina. Þessar niðurstöður gera rétta og snemmtæka greiningu augnlækna á augnsjúkdómum, hvort sem til eru við þeim meðferðir eða ekki, mjög mikilvæga fyrir sálarheill þeirra sjúklinga sem í hlut eiga og möguleika þeirra á að njóta viðeigandi aðstoðar og þjónustu. Til dæmis með því að vísa þeim til Þjónustu og þekkingarmiðstöðvar fyrir blinda, sjónskerta og daufblinda einstaklinga.

Þekkingu fleygir fram
Nú er það svo að hrörnunarsjúkdómar í sjónhimnu eru fáséðir sjúkdómar. Talið er að nýgengi þeirra sé á bilinu 1/3000 – 1/3500. Það er því ljóst að þessir sjúkdómar eru ekki oft að koma fyrir augu augnlækna.

Á undaförnum árum hefur þekkingu á eðli þessara sjúkdóma fleygt fram og nú er svo komið að fjölmargar klínískar sjúklingatilraunir eru við það að fara í gang,   þegar hafnar eða jafnvel komnar vel á veg. Um er að ræða tilraunir með genameðferðir, stofnfrumumeðferðir, tilraunir með rafeindasjón og lyfja- og taugafrumumeðferðir, svo eitthvað sé nefnt. Þegar fyrstu meðferðirnar koma á almennan markað, sem gæti verið innan 5 ára, að mati þeirra sem eru bjartsýnir, munu þeir sjúklingar standa best að vígi sem hafa rétta og nákvæma greiningu. Ýmislegt bendir einnig til þess að meðal fyrstu og aðgengilegustu meðferðanna verði fyrirbyggjandi meðferðir sem muni stöðva eða hægja allverulega á hrörnunarferlinu. Verði það raunin eykst mikilvægi snemmtækrar og réttra greininga ennþá meira.

Aukin árvekni
Um allan hinn vestræna heim kalla samtök þeirra sem eru með þessa augnsjúkdóma nú eftir aukinni árvekni augnlækna við skimun og greiningu þessara arfgengu hrörnunarsjúkdóma í sjónhimnu. Með réttri og snemmtækri greiningu aukast möguleikar sjúklinga á því að geta notið réttrar meðferða þegar þær vonandi fara að líta dagsins ljós á næstu 5 – 10 árum.    

Þar sem engin von var gefin fyrir 15 – 20 árum er núna von.

Kristinn Halldór Einarsson
Formaður Blindrafélagsins,
samtaka blindra og sjónskertra á Íslandi

Til hamingju Einar

Morgunblaðið segir frá því í frétt að Einar Stefánsson prófessor við læknadeild Háskóla Íslands, hafi verið sæmdur gullmedalíu evrópsku augnlæknaakademíunar og jafnframt verið tekinn inn í akademíuna. Full ástæða er til að óska Einar til hamingju með þessa viðurkenningu.

Þessi frétt vekur athygli á því að hversu mikið er í gangi á sviði rannsókna í augnvísindum og hef ég reynt að gera hluta af því skil hér á þessari síðu. Eðli málsins samkvæmt þá eru allar þessar rannsóknir að fást við að leita lækninga við augnsjúkdómum sem valda óafturkræfum sjónmissi. Í seinustu bloggfærslu minn birti ég framvindu skýrslu yfir rannsóknir sem gerð var grein fyrir á ársfundi AVRO(The Association for Research in Vision and Ophthalmology,) sem haldinn var í Fort Lauderdale í Bandaríkjunum 1 - 7 maí sl. Skýrsla þessi var sérstakeiga tekin saman fyrir Retina International,  sem hafa undanfarin 30 ár beitt sér fyrir rannsóknum á þessu sviði. Það er rétt að hafa í huga að þær rannsóknir sem nú eru í gangi eru tímafrekar og mörg ár geta liðið þar til í ljós kemur hvort að þær skila almennum meðferðum.

Einar Stefánsson heiðraður

Augnsjúkdómar - Framvinduskýrsla augnrannsókna frá ársfundi AVRO 2009

Hér má lesa skýrslu (á ensku) frá ráðstefnu og ársfundi AVRO (The Association for Research in Vision and Ophthalmology,) sem haldinn var í Fort Lauderdale í Bandaríkjunum 1 - 7 maí sl. Í þessari skýrslu má lesa að rannsóknir sem nú eru í gangi gefa vonir um að meðferðir gagnvart ólæknandi augnsjúkdómum, sem valda alvarlegri sjónskerðingu eða jafnvel blindu, eru að færast nær. Þessar niðurstöður eru afrakstur margra ára og áratuga grunnrannsókna og þekkingaröflunar. Þessi skýrsla var sérstaklega tekin saman fyrir Retina Intarnational. Af gefnu tilefni vil ég hvetja þá sem eru í samskiptum við augnlækna hér á landi vegna augnsjúkdóma, að bera skýrsluna undir sinn augnlækni, ef til umræðu er hvort mögulegar meðferðir muni verða til í framtíðinni og hvort eitthvað af því sem fjallað er um í skýrslunni geti hugsanlega komið að gagni. Varðandi þá sem eru með RP vil ég sérstaklega benda á umfjöllunina um RetinaComplex bætiefnið. 

Retinal Disease: Progress Reports from the Twelfth Annual Vision Conference and the ARVO 2009 Annual Meeting

Prepared by Elaine A. Richman, Ph.D., Richman Associates, LLC, USA

The reports below were prepared exclusively for Retina International. They are based on presentations made by scientists and clinicians at the Twelfth Annual Vision Conference (“Mechanisms of Macular Degeneration”) and the ARVO 2009 Annual Meeting, in Ft. Lauderdale, Florida, held consecutively from May 1 – 7, 2009. The range of topics included artificial vision, genetic influences on disease processes, interventions to control disease, retinal cell imaging, and countless others related to possible causes, treatments, and cures for retinal degenerative diseases. Many possible explanations are emerging. Some may turn out to be relevant to one condition and not another, or in one animal model and not another. Regardless, the many possible explanations reflect progress in understanding retinal degenerative conditions. 

More clues to rod and cones survival in RP

Connie Cepko from Harvard Medical College and her colleagues are working to understand the relationship between rod and cone photoreceptor death in retinitis pigmentosa (RP). Typically, a gene variant in rods causes the rod cells to die. But why, then, do cones also succumb? The researchers’;; work with mice suggests that part of the answer might relate to a protein called HDAC4: reduction in HDAC4 during normal retinal development causes rods to die; in a mouse model of retinal degeneration, supplementation with HDAC4 extends rod and cone cell survival. Related to cone death, they found a possible relationship between cone death and decreased activity of an insulin signaling pathway and perhaps nutrient depletion. Giving insulin to mice with retinal degenerative disease provided a degree of cone survival. Removing insulin accelerated cone demise. Ultimately, these findings could lead to development of therapies for intervening at various stages of RP.

Is cone death in RP caused by “starvation”?

Claudio Punzo of Harvard Medical School says that cone death in retinitis pigmentosa (RP) could be caused by starvation and explains why he believes this is so, related to the observations about insulin mentioned above.  He and colleagues studied four types of mice with gene mutations that cause rod photoreceptor cell death. The researchers looked at subsequent onset of cone death and found it associated with the insulin/TOR pathway, a regulator of cell growth. Conversely, when they provided cones with additional insulin, the cones survived. Hence, their thinking that cone cells in RP starve to death. (Insulin is needed to transport the nutrient glucose into cells.) They further suggest that the rod death leads to a perturbation in the cone-RPE relationship. The RPE (retinal pigment epithelium) is the source of nutrients to the photoreceptor cells. In all four types of mice, the cones began to die when approximately the same density of rods was observed. Punzo does not suggest insulin treatment for RP; rather it was used in this study to bolster the starvation theory of cone involvement in RP. 

Oxidative damage as another variable in rod and cone death in RP

Rods in the retina use a lot of oxygen. When they die in RP, the amount of oxygen in other portions of the retina goes up and causes oxidative damage to cones. It would make sense, therefore, that treatment with anti-oxidants would spare the cones. The logic of this approach is what Peter Campochiaro of Johns Hopkins University described in pigs and in mouse models of RP. The researchers are examining various drugs for inhibiting oxidative damage. They are also looking at gene therapies to improve patients’;; own anti-oxidant resources for prolonging cone survival. A combination of drug and gene therapy might be the most effective.

A role for a growth factor, too, in cone death in RP

Researchers have identified a protein that increases cone photoreceptor survival in rodent models of retinitis pigmentosa. The protein is a growth factor known as rod-derived cone viability factor (RdCVF). It appears to be involved in the defense against oxidative stress. When the growth factor was used to treat rats with autosomal dominant RP, their retinas showed not only more cone cell survival but also an unusual amplitude in retinal electrical activity. RdCVF was delivered by injecting the protein intraocularly or by delivering the protein-making gene using an adeno-associated virus delivery system. Jose-Alain Sahel of INSERM and his colleagues are looking at how this viability factor is tied to oxidative stress and to the function and survival of cone photoreceptors.

Retinal progenitor cells to replace photoreceptor cells

Research continues into ways to replace photoreceptor cells using retinal progenitor cells in retinitis pigmentosa and other degenerative retinal diseases where vision loss is due to photoreceptor cell death. It has been shown in animal studies that transplanted retinal progenitor cells (RPCs) from fetal, newborn, or adult animals are capable of migrating throughout the degenerating retina, becoming nerve cells, integrating into the retina and circuitry of the central nervous system, and even responding to light. The maturation and survival of RPCs appears to be dependent on numerous intrinsic and extrinsic factors. Also important are the source of the donor cells, their stage of development, their exposure to and regulation by various cellular and extracellular agents including those of the immune system, and the way these cells are delivered to the retina (e.g., by injection into the vitreous or subretinal space; on a synthetic scaffolding placed subretinally). Retinal transplant researcher Henry Klassen of the University of California at Irvine reminded the audience at ARVO 2009 that many other questions need answering before retinal cell transplant can become a viable therapy for replacing photoreceptor cells. The answers will require a multidisciplinary approach with experts not only from molecular biology but also from tissue engineering and other fields..

Norman Radtke and colleagues recently reported potentially encouraging findings from a Phase 2 clinical studies where they transplanted neural retinal progenitor cell layers, with fetal retinal pigment epithelium attached, into the subretinal space beneath the macula of patients with RP. Some enhanced vision was reported, although other researchers including Marco Zarbin of the New Jersey Medical School suggest that the results may be explained by a diffusion effect where growth factors from the implanted tissues dispersed to surrounding viable tissue and enhanced the response rather than by replacement of lost photoreceptors.

Overriding a nonsense mutation for treating Usher syndrome 1c: commercial aminoglycosides and PTC124

At ARVO 2009, researchers from the Technion-Israel Institute of Technology and the University of Mainz in Germany described experimental compounds for treating the USH1C gene nonsense mutation that causes USH1, the most severe form of Usher syndrome. A nonsense mutation causes a halt to the production of the protein that a gene is normally programmed to make. The researchers investigated several compounds—commercial aminoglycosides (e.g. G418, paromomycin), modified aminoglycosides (NB30, NB54), and the novel compound PTC124—that show promise for treating other genetic disorders (e.g., cystic fibrosis, muscular dystrophy). The compounds work by inducing a read-through of the gene. In cultured cells and mouse retina with the Usher gene mutation, the researchers found that the commercial aminoglycosides and PTC124 successfully induced a read-through and restored protein expression and function in a dose dependent manner. Much more work is necessary to understand the toxicity and efficacy of these compounds.

High density parafoveal rings as possible endpoints in RP clinical trials

In drug trials for retinitis pigmentosa, to show efficacy, the U.S. Food and Drug Administration requires tests of visual field sensitivity and best corrected visual acuity. Researchers are looking at other clinical tests that might be even more sensitive to changes in disease progression. Alan Bird and his colleagues from London’;;s Moorfields Eye Hospital and UCL Institute of Ophthalmology found that the density of parafoveal rings, determined by fundus autofluorescence and correlated with pattern electroretinogram, indicate an area where cone function and the outer retinal layer, as indicated by optical coherence tomography, are preserved. As RP progresses, the rings grew progressively smaller. These parafoveal rings may be an additional endpoint for the FDA to consider in clinical trials of therapies for RP. 

RP, pregnancy, and breast feeding

Italian researcher Luca Iacobelli, of the Italian Institute of Neurotrauma, and colleagues reported at ARVO 2009 on the effect of pregnancy and breast-feeding on visual acuity in women with retinitis pigmentosa. The only statistically significant finding occurred when best corrected visual acuity at month one of pregnancy and at five months post-partum was compared. All the women were breast feeding and the researchers suggest a possible relationship between decreased visual acuity and depletion of vitamin A and docosahexaenoic acid (DHA) through the mother’;;s milk. Post- partum vitamin supplementation is advised.

Nanoparticle delivery of genes in Leber’;;s congenital amaurosis

Researchers, including Muna Naash, from the University of Oklahoma recently demonstrated the successful use of RPE65 nanoparticles (plasmids expressing human RPE65 cDNA compacted into rod-like particles with a lysine peptide conjugated to polyethylene glycol) for delivering a gene therapy for treatment of Leber’;;s congenital amaurosis, a retinal degenerative disorder caused by mutations on the RPE65 gene. Other researchers have succeeded in delivering versions of the RPE65 gene using a viral vector, most notably to eyes of Briard dogs carrying the RPE65 mutation. The nanoparticle approach has the potential to overcome limitations of viral vectors including random integration into the host genome, inflammation, and more severe outcomes including death. It also demonstrates superiority over other non-viral gene delivery approaches (e.g., liposomal delivery, electroporation of naked DNA) in its transfection ability and duration of expression, say the researchers. The findings indicate that successful and sustained gene expression and functional improvement can be attained using the nanoparticle approach.

Promising results from Sirion for treatment of geographic atrophy

Sirion Therapeutics, Inc., recently announced interim results from its Phase 2 clinical trial of their drug fenretinide for the treatment of geographic atrophy (GA) associated with dry age-related macular degeneration. The positive results put the drug on a fast-track with the U.S. Food and Drug Administration. “The benefits of Fast Track include scheduled meetings to seek FDA input into development plans, the option of submitting a New Drug Application in sections rather than all components simultaneously, and the option of requesting evaluation of studies using surrogate endpoints.” (http://www.accessdata.fda.gov/scripts/cder/onctools/Accel.cfm#FastTrack) Fenretinide, provided in pill form, is a vitamin A binding protein antagonist and may work by reducing the formation or effect of drusen under the retinal pigment epithelium. Patients with lesions of all sizes who received 300 milligrams of fenretinide daily had slower rates of growth of their geographic atrophy than patients in control groups. A Phase 3 trial with many more than the 245 subjects already studied is being planned. 

The “artificial retina” for stimulating vision lost to RP

Although photoreceptors cells die in RP, other neuronal cells of the retina remain capable of transmitting signals that reach the brain to be interpreted as vision. These cells, mainly retinal ganglion cells, if stimulated with enough electrodes in a fashion that is coordinated with light and shapes in the visual field, can provide patients with functional vision, or so researchers are hoping. Work is being done by several groups to develop a retinal implant that will electrically control these cells. Among these groups is one supported by the U.S. Department of Energy Office of Science. It is called the Artificial Retina Project and is under the leadership of Mark Humayun of the Doheny Eye Institute in Los Angeles. Another, called Retinal Implant AG, is led by Eberhart Zrenner of University Eye Hospital Tübingen.

The first retinal implant is attached to the surface of the retina (epiretinal). The other, by Zrenner’;;s group, is subretinal.

With the epiretinal implant a stimulus in the visual field is captured by a tiny camera mounted on eyeglasses worn by the patient. The information is sent to a belt-worn microprocessor where it is converted to an electronic signal and transmitted to the retinal implant in a fashion that mimics patterns in the visual field. The stimulation sent to each electrode is independent of the signal sent to the other electrodes. The patterns of stimulation “seen” by the brain correspond to the spatial and temporal stimulation of the electrodes in the retinal implant. The researchers are testing a new 60-electrode unit and comparing the results to earlier tests of an implant consisting of 16 electrodes. Twenty-one people with advanced retinitis pigmentosa (little or no light perception), in the U.S., Mexico, Great Britain, France, and Switzerland, have been fitted with the newer unit.

A just released report describing the outcome in a patient with the 16-electrode epiretinal implant show that the device enabled him to detect patterns of stimulation (i.e., demonstrated when rows of electrodes at right angles were stimulated one row at a time; patient drew lines indicating pattern). Furthermore, when he was asked to view a video monitor showing high-contrast square-wave gratings, he could detect distances between lines that corresponded to the spacing between neighboring electrodes. All patients with the implants, the researchers reported, detected phosphenes when the electrodes are stimulated.

The sub-retinal implant, in contrast to the epiretinal implant, essentially replaces the photoreceptor cell layer with an implant having stimulus electrodes on its surface. There is no external camera or computer; all electronic components are placed under the retina in a 3 x 3 x0.1 mm chip, except a small power supply, connected by a thin cable, ending behind the ear. The researchers reported on an advanced transchoroidal technique for implanting their newest device, which consists of a 1500-electrode chip that is stimulated by light and 4 x 4 electrodes for direct stimulation. Despite the complexity of implanting the subretinal microelectrode array, no damage appears to occur to retinal tissue even in patients implanted up to three months. Patients report seeing a whitish round dot when individual electrodes are stimulated directly. When direct stimulation is presented in a pattern meant to represent a certain letter, some patients are able to correctly name the letter. By means of the light sensitive chip the most recent three patients were able to to discern the direction of fine stripes. One patient was able to read letters  4 to 8 cm in size presented on a table in regular reading distance under dim illumination, and combine them to words and recognize and precisely localize unknown objects such as a banana or an apple.

Many questions concerning electronic epiretinal or subretinal devices have yet to be answered with regard to device fabrication, packaging, and location, surgical technique for implantation, long-term tissue tolerance to the devices and to the unique electrical stimulation, characterization of ganglion cell activity, and much more. Basic, preclinical, and clinical studies continue in the hands of scientists involved with the Artificial Retina Project and Retinal Implant AG and also with others including Optobionics with its Artificial Silicon Retina (ASR) implant, IMI Intelligent Medical Implants AG with its Learning Retinal Implant System, and the EPI RET3 epiretinal array.

Ganglion cells engineered to respond to light successfully trigger a response in the visual cortex

Changing the behavior of one type of neuron in the central nervous system to take over the function of another type of cell is a huge challenge. Each cell has its own innate regulatory system and responsibility, which was considered immutable until recently. But the potential for such a toggle therapy for retinal degenerative diseases is huge. John Flannery of University of California, Berkeley, and his colleagues have found that they can confer light sensitivity (the typical venue of rod and cone photoreceptor cells) on retinal ganglion cells in cell culture, zebrafish larvae, and now mice. Using a viral vector they delivered an engineered light sensitive protein (the glutamate receptor, LiGluR) by intravitreal injection to retinal ganglion cells in a mouse model of retinal degeneration (rd-1 mice). They then stimulated the ganglion cells with light, studied the response in the brain’;;s primary visual cortex (V1), and found a robust response and light-evoked responses at all post-injection time points. The researchers conclude that LiGluR is worthy of study as a possible therapy for restoring light sensitivity in patients who are blind because of photoreceptor loss.

Algorithm predicts which RPE65 mutation causes pathogenicity

Ed Stone of the University of Iowa and his colleagues are looking at ways to differentiate disease-causing mutations from nonpathogenic gene polymorphisms to help patients and families with retinal disorders understand their risk and to help scientists plan clinical trials and explain varied outcomes in their research.  They have developed an algorithm that calculates an "estimate of pathogenic probability." It is based on the prevalence of a specific variation, its segregation within families, and its predicted effects on protein structure. Using the algorithm to evaluate 11 missense variations in the RPE65 gene of patients with Leber congenital amaurosis they were able to predict eight mutations as disease-causing variants. The algorithm may be useful to evaluate the pathogenicity of missense variations in other disease genes.

Warning of possible damage from fundus autofluorescence imaging of the RPE

Fundus autofluorescence (FAF) imaging is one of the newer techniques for examining the retina in health and disease. It identifies lipofuscin in retinal pigment epithelial cells and appears to provide information that cannot be gotten from other imaging techniques like fundus photography, fluorescein angiography, or optical coherence tomography. David Williams of the University of Rochester and his colleagues are finding that it may have a downside, however: possible damage to the retina from the blue light used in FAF imaging.

Lipofuscin derives mainly from uptake by RPE cells of photoreceptor degradation products. It fluoresces yellow when it is stimulated with light in the blue range. Lipofuscin accumulates with age and in certain retinal degenerative diseases. FAF imaging can be used to assess normal lipofuscin accumulation and also disease status in conditions such as Stargardt disease, Best’;;s vitelliform macular dystrophy, and age-related macular degeneration.

But when Dr. Williams’;; group examined the potential in monkeys for light-induced retinal damage from FAF , they found a deleterious effect at levels of light exposure that were even lower than the maximum permissible levels (MPE) set by the American National Standards Institute (ANSI). The fact that other clinical procedures such as slit lamp examination, fundus photography, fluorescein angiography, and retinal surgery are often performed at light levels close to the MPE makes the study potentially relevant across all of ophthalmology. Patients who have retinal disease, which may make them particularly vulnerable to blue light, should discuss with their physicians the importance of minimizing light exposure during retinal exams.

Gene Replacement Clinical Trials

UPenn Trial on LCA- RPE65 Gene Therapy – Dr. A. Cideciyan, University of Pennsylvania, Philadelphia, PA USA   

Preclinical studies on gene replacement therapy in animal models of Leber Congenital Amaurosis (LCA) were very successful. Specifically, the RPE65 gene was replaced in these cases using an AAV viral vector with excellent safety and efficacy that has restored a measure of sight in animals for a number of years. Based on this work, a Phase I clinical trial began in 2007 in LCA subjects with the RPE65 mutation with the approval of the FDA and support of the National Institutes of Health. The trial is led by Dr. Samuel Jacobson at the University of Pennsylvania in Philadelphia where the patients are first entered into the trial and examined before and after surgery. Surgery and gene-vector production occurs at the University of Florida under the leadership of Drs. William Hauswirth and Barry Bryne.

Dr. Artur Cideciyan gave an update on this trial. The primary outcome of the trial is safety; secondary outcomes include changes in vision. The trial was initially planned for 3 cohorts (groups) of patients, each with three individual subjects, The first cohort consisted of 3 young adults between 21 and 24 years of age. These patients received subretinal injections of the AAV2 vector with the normal RPE65 gene. The results available through the first 90 days post-treatment have been published and were encouraging. In terms of safety, there were no vector-related Serious Adverse Events (SAEs) and no systemic toxicities.  All patients self-reported and increase in visual sensitivity in their treated study eye compared with their control eye. This was especially noticeable under reduced ambient light conditions. Using a full-field stimulus test under dark-adapted conditions, the study eye showed significant sensitivity increases.

Specialized methods of vision testing corroborated that there were significant improvements in sensitivity localized to the area of treatment in the injected eye. The gene therapy procedure improved both day vision originating in cone photoreceptors as well as night vision originating in rod photoreceptors of the LCA patients. Day vision could be improved up to 50-fold and night vision up to 63,000-fold compared to pretreatment levels.

Dr. Cideciyan stated that the first cohort of patients has passed the 1-year time point and continue to do well. Specifically, there are no vector-related serious adverse events and the intervention appears to be safe. Based on the positive results in the first cohort, the Data Safety and Monitoring Committee has allowed the study to continue to the second cohort  which includes adults injected with a higher dose of vector and to the third cohort which includes children.                                                

CHOP Trial on LCA- RPE65 Gene Therapy

Dr. J. Bennett, University of Pennsylvania, Philadelphia, PA USA

     Dr. Bennet reported that at the Children’;;s Hospital of Philadelphia (CHOP) as well as in Naples, Italy and Ghent, Belgium, work continues on investigating the effects of RPE65 gene replacement in LCA subjects.

The first subject received a single unilateral subretinal injection of AAV2.hRPE65v2 in October of 2007 and, since that time, 10 additional individuals have been enrolled and received injections. Baseline testing, surgery and follow-up testing are carried out at CHOP. CLIA testing for the RPE65 mutation was done by Dr. E. Stone at the Univ. of Iowa.

The first 3 subjects enrolled (Naples, Italy) are young adults (19-26 yrs at the time of injection) and are now 15 months post-injection. They continue to do well as to both safety and efficacy. Duplicate baseline testing is now done at CHOP and in Naples serving to generate a robust data set.

Individuals enrolled over the last year include 4 children. All have recovered visual function with improvement in their nystagmus. They are reading without aids.

The upper age limit (72 yr) was eliminated in the protocol since a therapeutic effect was observed in the 26 yr old individuals in the first cohort. The oldest individual enrolled to date is 44 yr old.

All the juvenile and adult subjects are doing well. Two of these patients are from Ghent, Belgium so a third follow-up site is planned for this location.

In conclusion, Dr. Bennett said that the program in on target and the patients are happy with the results – all asking to have their second eye injected. 

RetinaComplex Clinical Study in Retinitis Pigmentosa Patients

Drs. Javier Romero and Theo van Veen, University CEU Cardenal Herrera and Mediterranean Ophthalmology Foundation, Valencia, Spain and University of Tuebingen, Tuebingen, Germany

Previous work by Prof. van Veen established the efficacy of using a combination of potent antioxidants called RetinaComplex in slowing the progression of retinal degeneration in animal models of RP. Please see the minutes from last year’;;s SMAB meeting for a position paper by Retina International on safety and efficacy issues in such use.

In the absence of Dr. Romero, Professor van Veen described the current clinical study. This is a hospital-based prospective, randomized double-blind clinical study with an appropriate control group being performed in Valencia, Spain. The first 12 months of the study have now been concluded with a total of 44 subjects with Retinitis Pigmentosa. 23 subjects received RetinaComplex and 21 subjects received placebo for 12 months. Written consent was obtained from the participants after they were given a reasonable explanation of the study details. A complete history of each participant with respect to age, gender, clinical symptoms, etc. was collected using a questionnaire.

Blood samples are collected to check for 1) glycosylated hemoglobin (a marker for metabolic control and possible diabetes) 2) zinc and vitamin E (to check for possible patient self-supplementation) and 3) malondialdehyde (a lipid peroxidation product that is a marker for oxidative stress).The fundus of each participant was exampled with an ophthalmoscope and macular OCT performed. Miltifocal ERG as well as other functional studies such as automated perimetry was performed and a general health evaluation questionnaire was obtained. All these baseline parameters are being compared with the same parameters obtained after 12 month RetinaComplex intake using appropriate statistical analysis.

From the intermediate data collected so far, no difference could be established between paired data, except for the amplitude of the multifocal erg. The placebo group showed a statistical difference between the data collected at the beginning of the study and the end of the first 12 month period. Of importance though, the patients receiving RetinaComplex showed no statistically significant difference between the two sets of data. This confirmsthat there is a slower progression of disease in the treated subjects compared with those getting only placebo. Although this study was initially planned for only 1 year, the promising results obtained makes it worthwhile to continue the study for a longer period if proper funding can be obtained.  The results of the first two years of the study will be available in autumn of this year. 

Neuroprotection Clinical Trials

CNTF-ECT Clinical Trials – Ms. Kathleen Dickinson – Neurotech, Lincoln, RI USA

CNTF is a natural compound found in the body that helps to protect neuronal cells from damage, hence is a “neuron-survival” and “neurotrophic” agent.  It has been shown to slow the course of retinal degeneration in a number of RD animal models. A problem with neurotrophic agents though is in the method of delivery to the retina. However, Neurotech has devised an ingenious capsule that is implanted within the vitreous cavity of the eye that delivers a sustained and safe dose of CNTF to the retina. This is called “Encapsulated Cell Technology” or NT-501-ECT. Preclinical experiments were successful using this device, showing relative safety as well as efficacy. Phase I of an FDA-approved trial also has successfully been completed.

Dr. Dickinson first apologized that Dr. Weng Tao, who was initially scheduled to give the Neurotech update was, at the last minute, unable to attend. She then proceeded to inform the group as to the current advanced-phase trials on subjects with RP and on those with Geographic Atrophy (GA). The trials are as follows: CNTF2 for dry AMD/GA; CNTF3 for late stage RP; CNTF4 for early stage RP. For example, 51 patients with dry AMD are being studied in the GA trial. To date in this ongoing work, the safety results are good in that Neurotech has encountered no significant treatment-related Serious Adverse Events (SAEs). No serum antibodies have developed against CNTF or the encapsulated cells that produce it. Dr. Dickinson reported that the biological effect of NT-501 has been identified. OCT images have demonstrated that there is improved definition of the Outer Nuclear Layer (ONL) of the retina in treated subjects at 12 months, compared to baseline images. A significant increase in retinal thickness, measured as total macular volume was determined by OCT. This was a dose dependent effect and observed in all three CNTF protocols. These results are consistent with published reports from preclinical observations. Retinal thickness was determined by the Duke Reading Center to not to be due to cystoid macular edema, epiretinal membrane formation, vitreoretinal traction or choroidal neovascularization.

Thus, the results appear to be encouraging such that CNTF-ECT might be the first treatment generally available to both RP and dry AMD patients. 

Úr fundargerð ársfundar vísinda og ráðgjafarnefndar Retina International

Þann  maí 4  var haldinn ársfundur Scientific and Medical Advisisory Board of Retina International í Fort Lauderdal í Kaliforníu. Á fundinn voru mættir margir af fremstu augnlæknum og vísindamönnum í fræðunum í dag.

Meðal þess sem má finna í fundargerðini er umfjöllun um RetinaComplex bætiefnið. Í þeirri umfjöllun segi m.a:.
 

„From the intermediate data collected so far, no difference could be established between paired data, except for the amplitude of the multifocal erg. The placebo group showed a statistical difference between the data collected at the beginning of the study and the end of the first 12 month period. Of importance though, the patients receiving RetinaComplex showed no statistically significant difference between the two sets of data. This confirms that there is a slower progression of disease in the treated subjects compared with those getting only placebo. Although this study was initially planned for only 1 year, the promising results obtained makes it worthwhile to continue the study for a longer period if proper funding can be obtained.  The results of the first two years of the study will be available in autumn of this year."

Í fundargerðinni er einnig fjallað um klínískar lyfjatilraunir bandaríska fyrirtækisins Neurotech. Í niðurlagi þeirrar umfjöllunar segir:

„Thus, the results appear to be encouraging such that CNTF-ECT might be the first treatment generally available to both RP and dry AMD patients" 

 

 

Íslenskur augnlæknir þátttakandi í merkilegri tilraun

Margir af þeim sem eru með RP augnsjúkdóminn, sem er arfgengur sjónhimnu hrörnunarsjúkdómur, hafa í nokkurn tíma vitað um störf Ragnheiðar Bragadóttur í Noregi. Ragnheiður er án vafa fremst meðal íslenskra vísindamanna þegar kemur að rannsóknum á RP. Mikill fengur væri af því að fá hana til landsins til að halda fyrirlestur um þær rannsóknir sem hún er þátttakandi í. Það er rétt að hafa í huga að sú aðferðarfræði sem þessar rannsóknir byggja á, þ.e. að nota veirur til að smita stökkbreyttar frumur með heilbrigðu geni, er eitthvað sem mun geta nýst á mun fleiri sviðum en í augnlækningum. Rannsóknin, sem er undir stjórn Robin Ali á Morfield sjúkrahúsinu þykir það merkileg að margar greinar hafa birtar um hana í virtustu læknatímaritum í heiminum. Með því að smella hér má lesa ein af þessum greinum.

Í júlí síðastiðnum gerði ég grein fyrir niðurstöðum frá ráðstefnu Retina International í Helsinki, en þar var umrædd rannsókn sérstaklega kynnt og er hún ein af ástæðum þess að meiri bjartsýni er nú ríkjandi meðal bæði vísinda og leikamanna að meðferðir og lækningar á áður ólæknandi augnsjúkdómum séu í sjónmáli,  á kanski næstu 10 - 15 árum. Umfjöllunina má sjá hér, en í henn er jafnframt gerð grein fyrir öðrum rannsóknum or tilraunum sem eru í gangi.

Fá hluta sjónar á ný

Byltingakenndar tilraunir á sjúklingum á sviði augnvísinda fá grænt ljós

Bandaríska fyrirtækið Neurotech hefur fengið leyfi bandarískra yfirvalda (FDA) fyrir byltingakenndum tilraunir á sjúklingum til meðferðar á RP og ellihrörnun í augnbotnum (Dry AMD). Ellihrörnun í augnbotnum er algengasta örsök blindu á Íslandi og í hinum vestræna heimi. Meðferðarúrræði gagnvart RP hafa ekki verið til staðar og mjög takmörkuð gagnvart AMD. Vonast er eftir því að fyrstu niðurstöður þessara tilraun líti dagsins ljós næsta vor.

Í grein sem ég skrifaði á bloggsíðuna mína í júlí s.l. gerði ég í stuttu máli grein fyrir þessum tilraunum. Sjá hér. 

Hér fer fréttatilkynning frá Neurotech. 

Neurotech Granted Fast Track Designations from the FDA for NT-501 in Two Indications?Retinitis Pigmentosa and Dry Age-Related Macular Degeneration

Lincoln, RI (September 3, 2008) - Neurotech Pharmaceuticals, Inc., a privately-held biotechnology company focused on the development of sight-saving therapeutics for chronic retinal diseases, announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track designations for NT-501 for the treatment of visual loss in two indications? retinitis pigmentosa (RP) and the dry form of age-related macular degeneration (dry AMD). NT-501 is an intraocular, cell containing polymer implant designed to provide continuous, long-term release of the therapeutic protein Ciliary Neurotrophic Factor (CNTF) directly into the back of the eye by means of the Company's proprietary Encapsulated Cell Technology. CNTF, a well established neurotrophic factor, rescues dying retinal photoreceptors and protects them from degeneration.

"We remain on track to announce top line results from our two Phase 2/3 studies in RP and our Phase 2 study in dry AMD by early 2009," said Ted Danse, President and CEO of Neurotech. "The receipt of Fast Track designations for NT-501 in these indications is an important component in our ongoing product development strategy, allowing us to potentially accelerate our two clinical development programs as we seek to provide much needed treatment options for patients facing these devastating diseases."

The Fast Track program, established under the FDA Modernization Act of 1997, provides for expedited regulatory review of a drug that demonstrates the potential to address an unmet medical need for the treatment of serious or life-threatening conditions. Under the program, the FDA will take such actions as are appropriate to expedite the development and review of the application for approval of such product, including potentially accepting, on a rolling basis, portions of the marketing application for review prior to the completion of the final registration package.

About Neurotech's Clinical Programs

Phase 2/3 Studies in Retinitis Pigmentosa (RP)
Neurotech is conducting two Phase 2/3 trials of NT-501 for the treatment of visual loss associated with RP-one consisting of patients with earlier stage disease (60 patients) and the second consisting of patients with later stage disease (60 patients). Both trials are randomized, multi-centered, double-masked, sham-controlled dose ranging studies. Each patient receives either a high or low dose NT-501 implant in one eye an  a sham treatment in the fellow eye. The primary efficacy endpoint is visual field sensitivity for the early-stage RP study and best corrected visual acuity for the late-stage RP study.

Phase 2 Study - Dry Age-related Macular Degeneration (Dry AMD)
This randomized, multi-centered, double-masked, sham-controlled study is evaluating NT-501 in 48 subjects with an advanced stage of dry AMD called geographic atrophy. Each subject receives either a high or low dose NT-501 implant or a sham treatment in one eye only. Best corrected visual acuity is the primary efficacy endpoint of this study.

About the Diseases
Retinitis Pigmentosa (RP) is an inherited disease that causes the retina's rod and cone photoreceptors to gradually degenerate leading to loss of vision and blindness. The symptoms of RP predominately appear in young adults and affect approximately 100,000 people in the United States and over 1 million people worldwide. At this time there is no known cure or effective treatment for RP.

Age-related macular degeneration (AMD) is a chronic progressive disease of the macula that results in the loss of central vision. It is the leading cause of blindness in elderly people in the developed world. There are two forms of AMD?dry and wet. Dry AMD is the most common form of AMD representing approximately 90% of all AMD cases. In its later stages dry AMD can lead to the degeneration of photoreceptors and retinal pigment epithelial cells, a chronic condition called geographic atrophy (GA). GA affects approximately 1 million people in the United States for which there currently are no effective treatments.

About Encapsulated Cell Technology
Neurotech's core technology platform is Encapsulated Cell Technology (ECT), a unique technology that allows for the long term, sustained delivery of therapeutic factors to the back of the eye. ECT implants consist of cells that have been genetically modified to produce a specific therapeutic protein and are encapsulated in a semi-permeable hollow fiber membrane. The diffusive characteristics of the hollow fiber membrane are designed to promote long-term cell survival by allowing the influx of oxygen and nutrients while simultaneously preventing direct contact of the encapsulated cells with the cellular and molecular elements of the immune system. The cells continuously produce the therapeutic protein which diffuses out of the implant at the target site. ECT therefore enables the controlled, continuous delivery of therapeutic factors directly to the retina, bypassing the blood-retina barrier.

About Neurotech Pharmaceuticals, Inc.
Neurotech is developing sight-saving therapeutics for the treatment of chronic retinal diseases. The Company's lead product candidate, NT-501, is currently in late-stage clinical development for retinitis pigmentosa (RP) and dry age-related macular degeneration (dry AMD). RP is the leading inherited cause of blindness for which there is no current treatment. The Company's portfolio of product candidates also includes treatments for wet AMD and diabetic macular edema. All of Neurotech's development programs are based on the Company's proprietary Encapsulated Cell Technology (ECT). ECT uniquely enables the controlled, continuous delivery of biologics directly to the back of the eye, overcoming a major obstacle in the treatment of retinal disease.

MEDIA CONTACT:
Rich Small
Vice President, CFO
Neurotech Pharmacuticals, Inc.
[e-mail]
http://neurotechusa.com/

 

Einar Stefánsson fær verðlaun á sviði augnrannsókna

Það er ástæða til að óska Einari Stefánssyni og samstarfsmönnum hans til hamingju með Jules Gonin verðlaunin sem veitt eru fyrir framúrskarandi árangur á sviði augnrannsókna. Þetta er enn eitt dæmið um þá framþróun sem á sér stað í  augnvísindum. Mér er ljúft að geta þess hér að Blindrafélagið hýsir hluta af þeim rannsóknum sem hér eiga í hlut í húsnæði sínu að Hamrahlíð 17. 

Einar Stefánsson fær verðlaun á sviði augnlækninga

Vinna andoxunarefni gegn arfgengri hrörnun í sjónhimnu?

Vísindamenn eru farnir að hvetja þá sem eru með RP að taka inn ákveðna samsetningu andoxunarefna, því líkur séu á því að það komi að gagni við að hægja á þróun hrörnunarferlisins án þess að hafa í för með sér alvarlegar aukaverkanir. 

Á ráðstefnu Retina International í Helsinki hitti ég konu frá S-Afríku sem sagði frá því að í hennar tilviki hefði hrörnunarferlið stöðvast frá þeim tíma þegar hún hóf inntöku þessara andoxunarefna. Mælingar augnlæknis hefðu staðfest þetta.

Þessi andoxunarefni eru nú fáanleg og heita RetinaComplex.    

Á fundi vísindanefndar Retina International (SMAB) sem var haldinn  í apríl síðast liðnum var samþykkt yfirlýsing varðandi notkun andoxunarefna gegn RP.

Hér fer lauslegri þýðingu á yfirlýsingunni, fyrir neðan er enska útgáfan:

"Óháðar niðurstöður frá vel virtum rannsóknaraðilum eru samdóma um að ákveðin blanda af andoxunarefnum séu árangursrík til að hægja á þróun hrörnunar í sjónhimnu í tilraunadýrum. Jákvæða viðbrögð í öllum þessum tilraunadýrum gefa til kynna að notkun andoxunarefna geti gefið góða raun sem meðferð við RP og öðrum tengdum sjúkdómum

Öryggisatriði meðferðarinnar í dýratilraununum hafa sýnt sig vera í lagi, auk þess sem efnin sem eru notuð eru þekkt fyrir að vera örugg fyrir menn og eru ekki efni sem eru flokkuð sem lyf.

Retina International hlakkar til að sjá niðurstöður klínískrar rannsóknar á mönnum, um notkun andoxunarefna til að hægja á hrörnunarferli í sjónhimnu, sem nú eru í gangi í Mediterranean Ophthalmology Foundation, Valencia, Spain (Prof. F.J. Romero)".

 

At the Annual Retina International Scientific and Medical Advisory Board [SMAB] meeting held at the ARVO congress in April the board issued the following statement on the use of anti oxidants for RP:

"Independent evidence from well respected laboratories agrees that combinations of antioxidant supplements are successful in slowing retinal degeneration in RD animal models. Positive effects in all these animal models may indicate that such treatment could be effective in most or all forms of RP and allied diseases irrespective of molecular diagnosis.

Safety seems assured from the animal testing done to date and from the fact that the supplements used are known to be well tolerated in humans and are not controlled substances.

Retina International looks forward to the results of human clinical studies for this promising treatment to slow the progression of Retinal Degeneration. These studies are ongoing at the Mediterranean Ophthalmology Foundation, Valencia, Spain (Prof. F.J. Romero)".

Meðferðir við arfgengum hrörnunarsjúkdómum í sjónhimnu í nútíð og framtíð - Þriðji hluti

Hér er þriðji og seinasti hluti erindis Gerald J. Cahder (Ph.D.,M.D.hc - Chief Scientific officer,  Doheny Retina International USC Medical school í Los Angeles) á ráðstefnu Retina International í Helsinki 4 og 5 júlí, þar sem hann dró saman helstu niðurstöður úr þeim erindum sem flutt voru á ráðstefnunni.

Ég biðst velvirðingar ef þýðingar eru ónákvæmar á einhverjum stöðum og bið um að viljinn sé tekinn fyrir verkið. Þessari þýðingu er ekki ætlað að vera lærður pistill heldur fyrst og fremst til upplýsinga fyrir þá sem eru með RP og aðra tengda sjúkdóma og fjölskyldur þeirra og vini.

Hér fer lausleg þýðing á þriðja og seinasta hluta ávarpsins:

"Hvaða klínsku rannsóknum má búast við í náinni framtíð á sjaldgæfari sjúkdómum

Nokkrir rannsóknarhópar vinna nú að því að koma í gang tilraunum á nokkrum af sjaldgæfari sjúkdómum.

1. Leber congenital amaurosis (LCA):Þrír rannsóknarhópar hafa hafið klínískar tilraunir í genameðferð þar sem gölluðu geni er skipt út fyrir heilbrigt gen í sjúklingum með ákveðna tegund af LCA. Að minnsta kosti einn hópur til viðbótar er einnig með klíníska rannsókn í undirbúningi.
2. Stargard: Dr. Rando Allikmets er ásamt samstarfsmönnum sínum að gera tilraun með að skipta út stökkbreyttu geni sem veldur Stargad fyrir heilbrigt gen í nagdýrum. Fram til þessa eru hafa eingöngu bráðabyrgða niðurstöður fengist, en þær lofa góðu. Ef tilraunin reynist vera örugg og árangursrík þá mun undirbúningur undir klínískar rannsóknir hefjast.
   Fleiri rannsóknarhópar eru í svipuðum sporum.
3. Usher sjúkdómar:  Rannsóknarhópar vinna nú að genameðferð á Usher1 og Usher3 með tilraundýrum.
   Vandamál hefur verið að fá góð tilraunadýr, það vandmál hefur nú verið leyst.
   Dr. Flannery hefur skýrt frá því að árangur er að nást.
4. Choroideremia:Vísindamenn eru nálægt því að fá nagdýr til að nota sem tilraundýr með choroideremia sjúkdóminn. Genameðferð með tilraundýrin er í undirbúningi. Ef þær reynast árangursríkar þá getur undirbúningur undir klínískrar tilraunir með sjúklinga hafist.
5. Samsvarandi tilraunir eru í gangi varðandi aðra sjaldgæfa sjúkdóma svo sem eins og Retinoschisis.

Hvað með ellihrörnun í augnbotnum (AMD)?
Núverandi AMD meðferðir

Þurr AMD- Bætiefnameðferð. Andoxunarefnin sem voru rannsökuð í klínískri rannsókn AREDAS eru nú fáanleg.

Vot AMD - Nokkur lyf hafa verið samþykkt af viðkomandi yfirvöldum í þó nokkrum löndum, sem er ætlað að hægja á nýmyndun afbrigðilegra æða. Best þekkta lyfið er Lucentis.

Bætiefni og ellihrörnun í augnbotnum (Dry AMD)
AREDAS tilraunin með andoxunarefni

• National Eye Institude (USA) hefur lokið við tilraun þar sem AMD er meðhöndlað með bætiefnum (andoxunarefnum). Tilraunin var nefnd AREDS (Age-related Eye disase study)
• Tilraunin sýndi fram á að að ákveðin bætiefni voru hjálpleg gagnvart AMD. Andoxunarefnin sem voru rannsökuð voru: B-carontene, og C-vítamín, E-vítamín ásamt zinki.
• Þessi andoxunarefni náðu aðeins að hægja á ferlinu á ákveðnu stigi sjúkdómsferilsins, þ.e. um miðbik.
• Þessi andxunarefni eru komin í sölu en rétt er að leita ráða hjá lækni áður en inntaka hefst.

Klíniskar meðferðir - vot ellihrörnun í augnbotnum (Wet AMD)

• Lyfið Lucentis virkar á vota ellihrörnun í augnbotnum. Lyfið virkar gegn VEGF, próteini sem veldur myndun nýrra afbrigðilegra æða í augnbotnum. Lyfið bætir sjón.
• Eitt af vandamálunum við Lucentis er að það þarf að sprauta því inn í augun.
• Annað vandamál er að það þarf að endurtaka meðferðin aftur og aftur.
• Þriðja vandamálið er síðan hversu dýrt lyfið er. Annað svipað lyf, Avastin, er fánlegra á mun lægra verði.  

AMD klínískar tilraunir - Klínískar genatilraunir

• Fyrirtækið GeneVec er með í gangi klíníska tilraun með genameðferð gegn votri ellihrörnun í augnbotnum. Í tilrauninni er PEDF geninu komið fyrir í auganu. Fyrsta stigi tilraunarinnar er lokið og voru öryggisniðurstöður mjög góðar.
• PEDF próteinið er náttúrulegt sem nýst getur bæði gegn AMD og RP.
• Ef niðurstöður tilraunarinnar verða jákvæðar þá eru líkur á að nota megi aðferðina gegn þurri ellihrörnun í augnbotnum (Dry AMD) og RP ásamt votri ellihrörnun í augnbotnum (Wet AMD).    

Klínískar rannsóknir á votri ellihrörnun í augnbotnum

Nokkur önnur efni sem hamlað geta gegn nýmyndun afbrigðilegra æða  í augnbotnum. Sem dæmi má nefna:

• Fyrirtækið Oxigene er með efnið Combretastatin, sem nýtt hefur verið gegn nýæðamyndun í krabbameinsmeðferð.
• Þetta efni er nú í klínískri tilraun gegn votri ellihrörnun í augnbotnum.
• Efni má gefa í æð og því nokkuð öruggt.
• Önnur sambærileg efni eru í þróun.

AMD klínískar rannsóknir - Bætiefni

• Bætiefnatilraun sem kallast AREDS2 með Lutein er nú í gangi á nokkrum AMD sjúklingum undir stjórn National Eye Institution (USA).
• Lutein/Zeaxanthin er efni sem unnið er úr litarefnum ávaxta og grænmetis og virkar sem andoxunarefni og er ætlað að verja ljósnemanna fyrir skemmdum af völdum súrefnis.
• Þetta er rannsóknir sem mun taka mörg ára að ljúka.
• Þangað til er rétt að fara að ráðum mömmu og borða ávexti og grænmeti.

Niðurstöður

Þó nokkrar klínískar tilraunir á hinum mismunandi hrörnunarsjúkdómum í augum eru nú í gangi, eða við það að hefjast.

Til dæmis þá hafa genameðferðir í dýrum með RP sýnt mjög jákvæðar niðurstöður, ekki eingöngu að sjón hafi náðst til baka heldur voru  langtímaáhrifin mjög jákvæð. Er hér komin lækning?

Grunnrannsóknir sem snúa að genameðferð, lyfjameðferð, bætiefnum og rafeindasjón eru mjög lofandi og nokkrar klínískar tilraunir eru þegar hafnar.

Rafeindasjón gæti verið besti möguleiki þeirra sem eru blindir eða mjög alvarlega sjónskertir til að öðlast aftur sjón.

Að lokum

• Í dag getum við meðhöndlað og jafnvel læknað tilraunadýr með margs konar hrörnunar sjúkdóma í sjónhimnu.
• Margar klínískar rannsóknir eru að hefjast þannig að meðferðir geta verið framundan.
• Allt er þetta mjög dýrt og tekur langan tíma....... en hver treystir sér til að setja verðmiða á að fá aftur glataða sjón."

  

Skrár tengdar þessari bloggfærslu:

• Gerald J. Cahder Helsinki 3hl.

Meðferðir við arfgengum hrörnunarsjúkdómum í sjónhimnu í nútíð og framtíð - Annar hluti

Hér er annar hluti erindis Gerald J. Cahder (Ph.D.,M.D.hc - Chief Scientific officer,  Doheny Retina International USC Medical school í Los Angeles) á ráðstefnu Retina International í Helsinki 4 og 5 júlí, þar sem hann dró saman helstu niðurstöður úr þeim erindum sem flutt voru á ráðstefnunni.

Ég biðst velvirðingar ef þýðingar eru ónákvæmar á einhverjum stöðum og bið um að viljinn sé tekinn fyrir verkið. Þessari þýðingu er ekki ætlað að vera lærður pistill heldur fyrst og fremst til upplýsinga fyrir þá sem eru með RP og aðra tengda sjúkdóma og fjölskyldur þeirra og vini.

Hér fer lausleg þýðing á öðrum hluta ávarpsins. Ávarpið mun verða sett fram í þremur hlutum.

"Klinkskar tilraunir í nútíð og framtíð

Nú skulum við beina athygli okkar að tveimur meðferðarúrræðum þegar fáir eða engir ljósnemar eru eftir á lífi.

Möguleg meðferðarúrræði í slíkum tilvikum gætu falist í:

• Ígræðsla ljósnema eða stofnfruma.
• Notkun rafeindasjónar.

Klínískar tilraunir með ígræðslu (transplantation) ljósnema

• Lengi hefur verið unnið að þeirri hugmyndin hvort hægt væri að skipta út dauðum ljósnemum fyrir nýja ljósnema.
• Lítil klínísk rannsókn á mönnum er nú í gangi með ígræðslu ljósnema. Rannsóknin er undir stjórn Dr. Norman Radtke í Bandaríkjunum.
• Tilraunin hefur sýnt að aðferðin virðist vera örugg, en því miður þá hafa niðurstöður ekki sýnt að aðferðin hafi bætt sjón hjá einstaklingum sem neinu nemur.

Með vísan til þess að eingöngu lítill, eða enginn árangur hefur náðst í að bæta sjón með þessum tilraunum, hjá bæði mönnum og dýrum, er erfitt að sjá að þessi tilraun muni leiða til árangurríkrar meðferðar í framtíðinni.

Ígræðsla stofnfruma (Transplantation: Stem Cells)

Rannsóknir á stofnfrumum og innsetningu þeirra er nýtt og mjög spennandi svið.

• Stofnfrumur er frumu sem hafa þann eiginleika að geta fjölgað sér og breyst í næstum því hvernig frumur sem er í líkamanum.
• Fræðilega séð mætti því setja stofnfrumur í sjónhimnuna þar sem eru dauðir ljósnemar og stofnfrumurnar ættu síðan að geta þróast í ljósnema og leyst af hólmi þá sem eru dauðir. 
• Hinsvegar þarf að gefa stofnfrumunum áveðin líffræðileg merki þannig að að þær þróist í að vera virkir ljósnemar sem koma að gagni, frekar en að þróast í einhverjar aðrar frumur.

Klínískar tilraunir með stofnfrumur

•  Fréttir hafa borist af því að tilraun þar sem stofnfrumur voru notaðar í tilraun með sjúkling hafi verið stöðvaðar í Bandaríkjunum. Fyrirtækið sem í hlut á hefur hins vegar ekki staðfest að stofnfrumur hafi verið notaðar.
• Fréttir hafa borist um að stofnfrumumeðferðir hafi verið stundaðar í einhverjum ríkjum. Litlar upplýsingar er hinsvegar að hafa um þessar meðferðir hvað varðar öryggi og virkni.
• Mun meiri rannsóknarvinna þarf að eiga sér stað áður en stofnfrummeðferð getur orðið raunhæft meðferðarúrræði við RP.

Rafeindasjón í stað glataðrar sjónar

Hér er um tvo flokka að ræða:

1. Ígræðslu rafeindaörflaga á heilabörk.
2. Ígræðslu rafeindaörflaga í sjónhimnuna -fyrir framan eða aftan sjónhimnuna.

Í tilvikum ígræðslu í sjónhimnu, þá eru margskonar nálganir og hannanir í gangi hjá hinum ýmsu hópum víða í heiminum.

Ígræðsla rafeindaörflaga á heilabörk

Þrír rannsóknahópar eru, eða hafa unnið, við að hanna rafeindasjón sem miðar að því fara algerlega framhjá augunum. 

• Einn hópurinn hefur þegar framkvæmt ótímabærar ígræðslu í menn með litlum árangri.
• Annar hópurinn einbeitir sér aðallega að grunn rannsóknum.
• Þriðji hópurinn hefur náð mjög góðum árangri með ígræðslur í apa og klínískar rannsóknir eru í undirbúningi.

Hvernig virkar rafeindasjón?

• Búnaðurinn notast við rafstraum til að fara framhjá gölluðum eða dauðum ljósnemum til að örva aðra hluta (nonphotorecptorcell) sjónhimnunnar.
• Myndir koma frá utanáliggjandi myndvél sem komið er fyrir bak við geraugu sjúklings.
• Myndirnar eru fluttar í gegnum tölvu til örflaga (eloctrodes called array) sem hafa verið græddar á sjónhimnuna til að endurskapa myndina sem send er til heilans.

   

 

Tilraunir með rafeindasjón

Hópar í mörgum löndum vinna að því að þróa rafeindasjón
Fjórir hópar víðs vegar um heiminn hafa þegar sett mismunandi hannaðan rafeindasjónbúnað í menn.  

• Optobionics Co. (Chicago, USA) - Slök hönnun þannig að búnaðurinn virkar illa eða alls ekki.
• Tvö mjög góð þýsk fyrirtæki - Fyrsta stig tilraun með menn í gangi - Retina Implant AG.
• Second Sight (Sylmar, Kalifornía USA) - Undir stjórn Dr. M.S. Humayun,  hefur ígræðsla átt sér stað í 6 sjúklinga á fyrsta stigi klínískrar tilraunar og meira en 10 sjúklingar hafa fengið ígræðslu á öðru stigi tilraunarinnar sem nýlega fór í gang.

Fyrsta stigs tilraunir á sjúklingum - Hvað hefur gerst

Samfelldar tilraunir hafa átt sér stað frá árinu 2002 á mönnum þar sem notast hefur verið við 16 örflögu búnað.

• Ígræðsla hefur átti sér stað hjá sex sjúklingum. Ekkert af búnaðinum bilaði.
• Allir sjúklingarnir náðu að sjá aðgreinda hluti (phosphenes) og gátu framkvæmt sjónræn verkefni í rými og hreyfingu.
• Hreyfanleiki og ferlihæfni batnaði.

Rafeindasjón - Framtíðin 

• Nokkrar klínískar tilraunir hafa verið settar í gang. Ef þær reynast árangursríkar er líklegt að tæki til almennra nota verði fáanleg í nánustu framtíð.
• Hönnun og tækni hefur fleygt fram í því að fjölga örflögum sem græða má á sjónhimnuna.
• Fræðilega þá er ljóst að það þarf 1000 örflögur til að skapa sjón nógu skrapa til lestrar og til að geta þekkt mannsandlit.
• Rafeindasjónin er kannski besti möguleiki, þeirra sem eru alvarlega sjónskertir eða blindir af völdum RP eða þurr AMD, til að öðlast sjón á ný.

Að lokum fyrir RP...

Nokkrar klínískar tilraunir eru í undirbúningi. Aðferðarfræði fyrir nokkrar aðrar tegundir meðferðar hafa verið sannprófaðar.

• Til dæmis, genameðferð á hundi, RP-LCA, sýndi ekki eingöngu að sjón sem var töpuð vannst til baka, heldur voru langtímaáhrifin mjög jákvæð.
• Aðrar grunnrannsóknir, á sviðum svo sem eins og genameðferð, stofnfrumurannsóknum, lyfjameðferð, bætiefnum og rafeindaörflögu innsetningu eru mjög lofandi fyrir klíniskar tilraunir í nútíð og framtíð."

Í þriðja hluta mun verða fjallað um sjaldgæfa augnsjúkdóma og ellihrörnunarsjúkdóma (AMD). 

 

Skrár tengdar þessari bloggfærslu:

• Gerald J. Cahder Helsinki 2hl.