By: PR Newswire
Nov. 17, 2008 09:01 AM
NEW YORK, MONTREAL and SAN DIEGO, CA, Nov. 17 /PRNewswire-FirstCall/ - Canadian Bio Med Systems Inc., a subsidiary of ICBS Limited (OTCPK: ICBT),) announced $10 million funding project for the development of two new drugs for age related macular degeneration (AMD) , and Glaucoma, being developed in conjunction with the university of Arizona .
Canadian Bio Med Systems, Inc. (CBMS) today announces that it is developing a drug to help cure the leading cause of blindness for persons over 50 years of age, for macular degeneration of the eye. The drug is being developed in conjunction with its partner Ocular Therapeutics, Inc. of San Diego, CA. The company has opened a $10 million dollar funding project through ICBS, which is targeting Federal funding along with private equity sources.
The company is currently involved in talks with a major Canadian University to work in conjunction with the University of Arizona. The company will also be taking advantage of the Research & Development grants offered by the Quebec and Canadian governments that will refund up to 70% of the companies R&D costs.
Wet age-related macular degeneration (AMD) is one of the leading causes of severe vision loss and blindness in the adult population. In the United States, there are more than 1.6 million cases of wet AMD and approximately 200,000 new cases of wet AMD are reported each year. A majority of wet AMD patients experience dramatic vision loss within months after diagnosis. Because AMD generally affects adults over 50 years of age, it is expected that the incidence of AMD will increase as the baby-boom generation ages and life expectancy increases and it has been estimated by the National Eye Institute that by 2030, an estimated 2.8 million Americans will suffer from visual impairment as a result of AMD.
While several treatment options for wet AMD are available, each has its disadvantages such as increased risk of stroke, failure to show improvement, and cost. There is no indication that any of these drugs is effective enough that it obviates the need for additional drugs to treat this disease, leaving the opportunity for novel new compounds to enter the market. The advantage of the drug under development at CBMS lies in the unique mechanism by which it manages the cause of AMD, inhibition of migration, which is distinct from the current treatments. This drug, therefore, will not compete directly with other marketed treatments and may be used as a replacement for or in conjunction with these therapies to increase the efficacy of treatment.
Glaucoma is the second most common cause of blindness in the United States, accounting for (greater than)11% of all cases of blindness in the country. The various glaucomas are estimated to affect (greater than)2.2 million individuals in the United States who are (greater than)40 years old with primary open angle glaucoma, the most common form. Glaucoma is the leading cause of blindness among African-Americans, and African-Americans are three to five times more likely to have the disease than Caucasians.
"These new compounds being developed by our two companies can be quite important in treating this very debilitating ocular diseases" said Dr. Richard Keates, MD, Chairman of Ocular Therapeutics. "Because of the unique method of action, it has the capability of becoming a very large component in the treatment of AMD and Glaucomas"
NB. This news release includes statements that constitute forward-looking statements. Please be aware that any such forward-looking statements are not guarantees of future performance and involve significant risks and uncertainties, and that actual results may vary materially from those in the forward-looking statements as a result of any number of factors, including the risk factors contained in the Company's disclosure documents.
SOURCE Inter Canadian Business Service
Saturday, November 22, 2008
My sister went to a naturopathic physician who gave her an intravenous infusion of nutrients. What's this all about?
Vitamins, minerals, and other nutrients are administered intravenously for a wide range of health conditions. It is a safe, inexpensive and effective means to deliver nutrients.
Why isn't oral supplementation sufficient?
Oral supplements and medication are convenient to take, but they are only as good as one's digestive and absorptive capabilities. When there are problems with digestion and assimilation, the recipient may be getting only a fraction of the intended benefit. When this happens, intravenous nutrients can be useful in treating illnesses that do not respond to other therapies. Additionally, some illnesses are best treated with nutritional concentrations higher than one could achieve with oral administration, and intravenous infusions can deliver a concentration of a nutrient that could not be obtained with an equivalent oral dose.
What conditions are treated with intravenous infusion?
Intravenous nutrition can be helpful in treating fibromyalgia, chronic fatigue and exhaustion. It is beneficial in supporting the immune system and treating the symptoms of the common cold, flu, and other viral illnesses. Macular degeneration and glaucoma are also improved with intravenous nutritional therapy as well as Parkinson's disease and arrhythmias of the heart. It has tremendous benefits is tissue and would healing, arresting asthma and as adjunctive treatment for many cancers.
Hanna Ian, M.S., N.M.D, is a naturopathic physician. She is in private practice at
The Naturopathic Physician located in Surprise. Reach Dr. Ian at 623-792-8889 or www.thenaturopathicphysician.com.
Why isn't oral supplementation sufficient?
Oral supplements and medication are convenient to take, but they are only as good as one's digestive and absorptive capabilities. When there are problems with digestion and assimilation, the recipient may be getting only a fraction of the intended benefit. When this happens, intravenous nutrients can be useful in treating illnesses that do not respond to other therapies. Additionally, some illnesses are best treated with nutritional concentrations higher than one could achieve with oral administration, and intravenous infusions can deliver a concentration of a nutrient that could not be obtained with an equivalent oral dose.
What conditions are treated with intravenous infusion?
Intravenous nutrition can be helpful in treating fibromyalgia, chronic fatigue and exhaustion. It is beneficial in supporting the immune system and treating the symptoms of the common cold, flu, and other viral illnesses. Macular degeneration and glaucoma are also improved with intravenous nutritional therapy as well as Parkinson's disease and arrhythmias of the heart. It has tremendous benefits is tissue and would healing, arresting asthma and as adjunctive treatment for many cancers.
Hanna Ian, M.S., N.M.D, is a naturopathic physician. She is in private practice at
The Naturopathic Physician located in Surprise. Reach Dr. Ian at 623-792-8889 or www.thenaturopathicphysician.com.
Age Related Macular Degeneration Therapy
(a) Laser Photocoagulation:
This procedure uses laser to destroy the fragile, leaky blood vessels. A high energy beam of light (argon or krypton laser) is aimed directly onto the new blood vessels and destroys them, preventing further loss of vision. Though thermal laser treatment has been shown beneficial at reducing the likelihood of developing severe visual loss, there is usually an immediate decrease in visual acuity especially in subfoveal choroidal neovascularization (CNV). A CNV membrane is described as subfoveal if any part of the lesion lies beneath the centre of the foveal avascular zone (FAZ). The concern of subfoveal lesions is due to the fact that photocoagulation of such a CNV membrane necessarily results in the destruction of the overlying retina.2 Moreover, thermal laser is effective only in a small subgroup of patients with small, well-demarcated lesions that include a component of classic CNV. Therefore, many alternatives to laser photocoagulation are evolving mainly for subfoveal CNV.
(b) Photodynamic Therapy (PDT):
In 2000, USFDA approved Visudyne™ (Verteporfin for injection) for the treatment of predominantly classic subfoveal choroidal neovascularization due to AMD, pathologic myopia or presumed ocular histoplasmosis. It was the first approved drug therapy for the treatment of wet AMD. Visudyne™ is injected systemically and activated by a non-thermal laser to destroy leaking vessels.3 This therapy utilizes low-intensity light exposure (689 nm, 50 J/cm2 dose, for 83 s in Verteporfin PDT) which causes selective destruction of CNV with preservation of the overlying neuro sensory retina. There are various photosensitizing agents available for treatment. However, currently only Verteporfin is approved for the treatment of CNV. 4 Patients who receive this therapy become temporarily photosensitive and should avoid direct sunlight for 5 days.
(c) Anti Vascular endothelial growth factor (anti-VEGF)
VEGF is a naturally occurring large lipoprotein molecule consisting of at least 6 structurally related proteins. Studies have shown elevated VEGF levels in areas of laser induce CNV in primates and clinically in AMD patients. Macugen (Pegabtanib) was approved in 2004 to treat wet AMD, and is used solely or in combination with other AMD treatments.
The drug Lucentis (Ranibizumab) was approved by FDA for treating AMD in June 2006. It is a humanized antibody fragment designed to bind and inhibit the action of VEGF and thus prevent blood vessel growth and leakage. Avastin (Bevacizumab) is a drug similar to Lucentis that is used to treat colon cancer. Ophthalmologists may prescribe Avastin off label for the treatment of AMD.
VEGF Trap is a substance that blocks the action of vascular endothelial growth factor (VEGF), and prevents the growth of new blood vessels in a tumor. It belongs to the family of drugs called angiogenesis inhibitors. Angiogenesis is the term used to describe the proliferation of blood vessel growth. Substances that stop the growth of excessive blood vessels are anti-angiogenic .Bayer Healthcare and Regeneron have initiated a Phase 3 study of the VEGF Trap -Eye in the neovascular form of wet AMD. 5
(d) Combination therapy of Triamcinolone and Verteporfin
Triamcinolone acetonide has been used to modify the process of choroidal neovascularization. Corticosteroids have a multitude of anti-inflammatory effects and also seem to have direct anti-angiogenic properties. Steroids have an inhibitory effect on angiogenesis, fibrotic activity and inflammatory reaction by reducing the migration and activation of inflammatory cells. Up-regulation of extracellular matrix protein plasminogen activator inhibitor by steroids results in direct angiostatic effect. Corticosteroids stabilize endothelial and basement membranes and also reduce vascular permeability with beneficial effects.
PDT provides immediate angio-occlusion of CNV and intravitreal triamcinolone acetonide (IVTA) , prevents inflammation and up-regulation of VEGF, decreases subsequent regrowth of CNV and finally improves VA outcome. This provides substantial reasons for using verteporfin and triamcinolone in combination. 6, 7,8
Significant improvements in best-corrected visual acuity (VA) after 1 month and their maintenance over a 3-month period were observed after verteporfin Photodynamic therapy combined with intravitreal bevacizumab. These results should be confirmed in larger and long-term prospective randomized trials. 9
Alternative Therapies:
(a) Radiation Therapy:
Radiotherapy affects the evolution of exudative macular degeneration directly by endothelial toxicity, leading to capillary closure and/or indirectly through its attenuating effects on the inflammatory response, mediated by macrophages and other inflammatory cells.10 Low-dose ionizing radiation has been shown to prevent proliferation of endothelial cells of newly formed subretinal capillaries and may induce destruction of abnormal CNV tissue.
(b) Submacular Surgery:
Surgical removal of CNV with large subfoveal hemorrhages can limit toxicity to overlying photoreceptors by prompt evacuation of blood . 11 By preserving the overlying neurosensory retina it can limit visual field defect enlargement and central vision loss.
Moreover,surgery may apply to a wide range of lesions and adjunctive procedures such as RPE transplantation. However, the risks with submacular surgery are considerable and include acceleration of cataract, development of retinal tears and retinal / choroidal detachments.
(c) Retinal translocation:
Retinal translocation and limited macular translocation are being used with rationale to move the macular area from the underlying CNV to a healthier RPE region. The Choroidal neovascular membrane can then be treated with laser photocoagulaton, while sparing the foveal center. 12 However, there is risk of development of intractable proliferative vitreoretinopathy, total retinal detachment, and unpredictable long-term visual prognosis.
(d) Transpupillary thermotherapy (TTT):
A slit lamp delivery system is used to project a beam of diode laser on the lesion thereby causing heat transmission to RPE and choroid. Studies by Reichel et al 13 showed benefit for patients with occult CNV in terms of improvement of visual acuity and decreased exudation.
Prevention:
There is evidence that dietary supplements can help prevent the onset and progression of age-related macular degeneration. Lutein and zeaxanthin is found in leafy green vegetables, corn, egg yolk, squash, broccoli and peas. These carotenoids are proposed to reduce the risk of AMD by absorbing the blue light that could damage the macula, by preventing free radicals from damaging eye cells and by strengthening eye cell membrane. 14
Undergoing Research
Research is in progress to transiently enhance vascular permeability in PDT to selectively release an anti-angiogenic or anti-inflammatory factor to prevent recurrence of neovasculature in case of AMD or to release chemotherapeutic agents in the case of PDT of a malignant tumour. 15
A study was done to evaluate the safety, efficacy & durability of systemic Bevacizumab therapy for neovascular ARMD. The results were good for a small group of patients however the risks associated with systemic anti-VEGF therapy versus the safety of intra vitreal therapy deters the involvement of a large number of patients. 16
Micro and nano particulates have been used primarily on a pre-clinical basis as new drug delivery devices in experimental models of neovascular AMD 17 .The development of polymeric micelles with smart functions such as environment-sensitivity and specific tissue-targetability may enhance the activity of potent bioactive compounds, facilitating their clinical applications. Also, polymeric micelles response to external stimuli, such as light, might exert the activity of the loaded compounds in a site-directed manner, ensuring the effectiveness and safety of the nanocarrier-mediated targeting therapy. Thus, polymeric micelle-based nanocarriers will continue to hold promise for the delivery of drugs and genes . 18
All types of nucleic acids have been developed for the treatment of infectious and cell proliferative diseases affecting mostly the posterior segment of the eye. The eye is therefore a good target for this type of molecules mainly because it is a confined compartment and their delivery is close to the target site. However, to improve the efficiency of such molecules, the use of controlled and/or targeted delivery systems is needed since they allow protection against degradation, increase intracellular penetration and permit long-term delivery avoiding repeated administrations. 19
Conclusion:
Early detection of AMD can stop the progress of the disease. Patients need to be educated about the condition and consistent follow up is required. Drug delivery to the posterior segment of the eye still remains a challenge. Rapid pre corneal elimination, poor corneal absorption, rapid anterior chamber elimination and large diffusional path lengths combine to prevent topically administered drugs from reaching the posterior segment of the eye.
Lot of research is being undertaken and many Pharmacophores are being investigated. A fundamental understanding of the patho physiology of AMD integrated with a mechanistic understanding of drug delivery to the posterior segment is requisite for the design of drugs and drug delivery systems for macular degeneration.
References:
1. Verma L, Das T, Binder S. Heriot W.J., New approaches in the management of choroidal neovascular membrane in age-related macular degeneration, Current Ophthalmology, (48) (4) (2000) 263-78.
2. Beatty et al, Photocoagulation of subfoveal choroid neovascular membrane in age related macular degeneration, British Journal of Ophthalmology (83) (1999) 1103-1104.
3.Orest O., Patrick H., Drug delivery strategies to treat age related macular degeneration, Advanced drug delivery reviews (57) (14) (2005) 1991-1993.
4. Kulkarni A. D., Kuppermann B. D., Wet age related macular degeneration, Advanced drug delivery reviews (57) (14) (2005) 1994-2009.
5. http://www.fiercebiotech.com/press-releases/press-release-bayer-healthcare-regeneron-initiate-phase-3-vegf-trap-
6. Kumar A., Visual acuity and contrast sensitivity outcomes in Indian eyes undergoing photodynamic therapy with intravitreal injection of triamcinolone acetonide in age-related macular degeneration, Indian journal of ophthalmology (55) ( 3)(2007) .
7.Gillies M. C. ,Sompson J. M. ,Luo W, Penfold P., Hunyor A. B.,Chua W., A randomized clinical trail of a single dose of intravitreal Triamcinolone Acetonide for neovascular age-related macular degeneration: One-year results. Arch Ophthalmol (121) (2003) 667-673.
8. Jonas J. B.,Kreissing I.,Hugger P., Sauder G , S. Panda-Jonas, Degenring R., Intravitreal triamcinolone acetonide for exudative age-related macular degeneration, British Journal of Ophthalmology (87) (2003) 462-468.
9.Lazic R., Gabric N., Verteporfin therapy and intravitreal bevacizumab combined and alone in choroidal neovascularization due to age-related macular degeneration, Ophthalmology (114) ( 6) (2007) 1179-1185.
10. Munshi A. , Age related macular degeneration: A study of patients managed with radiotherapy, Journal of cancer research and therapeutics (3) (1) (2007) 12-16
11. Lewis H , Intraoperative fibrinolysis of submacular haemorrhage with tissue plasminogen activator and surgical drainage, American.Journal of Ophthalmology (118) (1994) 559-568.
12. Potter M., Improvement in macular function after translocation surgery in a patient with age-related macular degeneration, American Journal of Ophthalmology (129) ( 4) (2000) 547-549
13. Reichel E.,Berrocal A. M ,Desai V., Duker J.S. ,Pulfiafito C. A, Transpupillary thermotherapy of occult subfoveal choroidal neovascularization in patients with age related macular degeneration, Ophthalmology (106) (1999) 1908-1914.
14. http:// www.nutraingredients .com Europe 16/08/2006.
15. Debefve E., Combination therapy using aspirin-enhanced photodynamic selective drug delivery, Vascular Pharmacology (46) (3) (2007) 171-180.
16. Rosenfeld J. P, Systemic bevacizumab (Avastin) Therapy for neovascular age-related macular degeneration twenty-four-week results of an uncontrolled open-label clinical study, Ophthalmology (11 ) (113) (2006) 2002-2011.
17. Moshfeghi A.A ,Peyman G. A., Micro and nano particulates, Advanced Drug Delivery Reviews (57) (14) (2005) 2047-2052.
18. Nobuhiro N; Current state, achievements, and future prospects of polymeric micelles as nanocarriers for drug and gene delivery, Pharmacology and Therapeutics (112) (3) (2006) 630-648.
19. Fattal E. , Ocular delivery of nucleic acids: antisense oligonucleotides, aptamers and siRNA, Advanced Drug Delivery Reviews (58) (11) (2006) 1203-1223.
This procedure uses laser to destroy the fragile, leaky blood vessels. A high energy beam of light (argon or krypton laser) is aimed directly onto the new blood vessels and destroys them, preventing further loss of vision. Though thermal laser treatment has been shown beneficial at reducing the likelihood of developing severe visual loss, there is usually an immediate decrease in visual acuity especially in subfoveal choroidal neovascularization (CNV). A CNV membrane is described as subfoveal if any part of the lesion lies beneath the centre of the foveal avascular zone (FAZ). The concern of subfoveal lesions is due to the fact that photocoagulation of such a CNV membrane necessarily results in the destruction of the overlying retina.2 Moreover, thermal laser is effective only in a small subgroup of patients with small, well-demarcated lesions that include a component of classic CNV. Therefore, many alternatives to laser photocoagulation are evolving mainly for subfoveal CNV.
(b) Photodynamic Therapy (PDT):
In 2000, USFDA approved Visudyne™ (Verteporfin for injection) for the treatment of predominantly classic subfoveal choroidal neovascularization due to AMD, pathologic myopia or presumed ocular histoplasmosis. It was the first approved drug therapy for the treatment of wet AMD. Visudyne™ is injected systemically and activated by a non-thermal laser to destroy leaking vessels.3 This therapy utilizes low-intensity light exposure (689 nm, 50 J/cm2 dose, for 83 s in Verteporfin PDT) which causes selective destruction of CNV with preservation of the overlying neuro sensory retina. There are various photosensitizing agents available for treatment. However, currently only Verteporfin is approved for the treatment of CNV. 4 Patients who receive this therapy become temporarily photosensitive and should avoid direct sunlight for 5 days.
(c) Anti Vascular endothelial growth factor (anti-VEGF)
VEGF is a naturally occurring large lipoprotein molecule consisting of at least 6 structurally related proteins. Studies have shown elevated VEGF levels in areas of laser induce CNV in primates and clinically in AMD patients. Macugen (Pegabtanib) was approved in 2004 to treat wet AMD, and is used solely or in combination with other AMD treatments.
The drug Lucentis (Ranibizumab) was approved by FDA for treating AMD in June 2006. It is a humanized antibody fragment designed to bind and inhibit the action of VEGF and thus prevent blood vessel growth and leakage. Avastin (Bevacizumab) is a drug similar to Lucentis that is used to treat colon cancer. Ophthalmologists may prescribe Avastin off label for the treatment of AMD.
VEGF Trap is a substance that blocks the action of vascular endothelial growth factor (VEGF), and prevents the growth of new blood vessels in a tumor. It belongs to the family of drugs called angiogenesis inhibitors. Angiogenesis is the term used to describe the proliferation of blood vessel growth. Substances that stop the growth of excessive blood vessels are anti-angiogenic .Bayer Healthcare and Regeneron have initiated a Phase 3 study of the VEGF Trap -Eye in the neovascular form of wet AMD. 5
(d) Combination therapy of Triamcinolone and Verteporfin
Triamcinolone acetonide has been used to modify the process of choroidal neovascularization. Corticosteroids have a multitude of anti-inflammatory effects and also seem to have direct anti-angiogenic properties. Steroids have an inhibitory effect on angiogenesis, fibrotic activity and inflammatory reaction by reducing the migration and activation of inflammatory cells. Up-regulation of extracellular matrix protein plasminogen activator inhibitor by steroids results in direct angiostatic effect. Corticosteroids stabilize endothelial and basement membranes and also reduce vascular permeability with beneficial effects.
PDT provides immediate angio-occlusion of CNV and intravitreal triamcinolone acetonide (IVTA) , prevents inflammation and up-regulation of VEGF, decreases subsequent regrowth of CNV and finally improves VA outcome. This provides substantial reasons for using verteporfin and triamcinolone in combination. 6, 7,8
Significant improvements in best-corrected visual acuity (VA) after 1 month and their maintenance over a 3-month period were observed after verteporfin Photodynamic therapy combined with intravitreal bevacizumab. These results should be confirmed in larger and long-term prospective randomized trials. 9
Alternative Therapies:
(a) Radiation Therapy:
Radiotherapy affects the evolution of exudative macular degeneration directly by endothelial toxicity, leading to capillary closure and/or indirectly through its attenuating effects on the inflammatory response, mediated by macrophages and other inflammatory cells.10 Low-dose ionizing radiation has been shown to prevent proliferation of endothelial cells of newly formed subretinal capillaries and may induce destruction of abnormal CNV tissue.
(b) Submacular Surgery:
Surgical removal of CNV with large subfoveal hemorrhages can limit toxicity to overlying photoreceptors by prompt evacuation of blood . 11 By preserving the overlying neurosensory retina it can limit visual field defect enlargement and central vision loss.
Moreover,surgery may apply to a wide range of lesions and adjunctive procedures such as RPE transplantation. However, the risks with submacular surgery are considerable and include acceleration of cataract, development of retinal tears and retinal / choroidal detachments.
(c) Retinal translocation:
Retinal translocation and limited macular translocation are being used with rationale to move the macular area from the underlying CNV to a healthier RPE region. The Choroidal neovascular membrane can then be treated with laser photocoagulaton, while sparing the foveal center. 12 However, there is risk of development of intractable proliferative vitreoretinopathy, total retinal detachment, and unpredictable long-term visual prognosis.
(d) Transpupillary thermotherapy (TTT):
A slit lamp delivery system is used to project a beam of diode laser on the lesion thereby causing heat transmission to RPE and choroid. Studies by Reichel et al 13 showed benefit for patients with occult CNV in terms of improvement of visual acuity and decreased exudation.
Prevention:
There is evidence that dietary supplements can help prevent the onset and progression of age-related macular degeneration. Lutein and zeaxanthin is found in leafy green vegetables, corn, egg yolk, squash, broccoli and peas. These carotenoids are proposed to reduce the risk of AMD by absorbing the blue light that could damage the macula, by preventing free radicals from damaging eye cells and by strengthening eye cell membrane. 14
Undergoing Research
Research is in progress to transiently enhance vascular permeability in PDT to selectively release an anti-angiogenic or anti-inflammatory factor to prevent recurrence of neovasculature in case of AMD or to release chemotherapeutic agents in the case of PDT of a malignant tumour. 15
A study was done to evaluate the safety, efficacy & durability of systemic Bevacizumab therapy for neovascular ARMD. The results were good for a small group of patients however the risks associated with systemic anti-VEGF therapy versus the safety of intra vitreal therapy deters the involvement of a large number of patients. 16
Micro and nano particulates have been used primarily on a pre-clinical basis as new drug delivery devices in experimental models of neovascular AMD 17 .The development of polymeric micelles with smart functions such as environment-sensitivity and specific tissue-targetability may enhance the activity of potent bioactive compounds, facilitating their clinical applications. Also, polymeric micelles response to external stimuli, such as light, might exert the activity of the loaded compounds in a site-directed manner, ensuring the effectiveness and safety of the nanocarrier-mediated targeting therapy. Thus, polymeric micelle-based nanocarriers will continue to hold promise for the delivery of drugs and genes . 18
All types of nucleic acids have been developed for the treatment of infectious and cell proliferative diseases affecting mostly the posterior segment of the eye. The eye is therefore a good target for this type of molecules mainly because it is a confined compartment and their delivery is close to the target site. However, to improve the efficiency of such molecules, the use of controlled and/or targeted delivery systems is needed since they allow protection against degradation, increase intracellular penetration and permit long-term delivery avoiding repeated administrations. 19
Conclusion:
Early detection of AMD can stop the progress of the disease. Patients need to be educated about the condition and consistent follow up is required. Drug delivery to the posterior segment of the eye still remains a challenge. Rapid pre corneal elimination, poor corneal absorption, rapid anterior chamber elimination and large diffusional path lengths combine to prevent topically administered drugs from reaching the posterior segment of the eye.
Lot of research is being undertaken and many Pharmacophores are being investigated. A fundamental understanding of the patho physiology of AMD integrated with a mechanistic understanding of drug delivery to the posterior segment is requisite for the design of drugs and drug delivery systems for macular degeneration.
References:
1. Verma L, Das T, Binder S. Heriot W.J., New approaches in the management of choroidal neovascular membrane in age-related macular degeneration, Current Ophthalmology, (48) (4) (2000) 263-78.
2. Beatty et al, Photocoagulation of subfoveal choroid neovascular membrane in age related macular degeneration, British Journal of Ophthalmology (83) (1999) 1103-1104.
3.Orest O., Patrick H., Drug delivery strategies to treat age related macular degeneration, Advanced drug delivery reviews (57) (14) (2005) 1991-1993.
4. Kulkarni A. D., Kuppermann B. D., Wet age related macular degeneration, Advanced drug delivery reviews (57) (14) (2005) 1994-2009.
5. http://www.fiercebiotech.com/press-releases/press-release-bayer-healthcare-regeneron-initiate-phase-3-vegf-trap-
6. Kumar A., Visual acuity and contrast sensitivity outcomes in Indian eyes undergoing photodynamic therapy with intravitreal injection of triamcinolone acetonide in age-related macular degeneration, Indian journal of ophthalmology (55) ( 3)(2007) .
7.Gillies M. C. ,Sompson J. M. ,Luo W, Penfold P., Hunyor A. B.,Chua W., A randomized clinical trail of a single dose of intravitreal Triamcinolone Acetonide for neovascular age-related macular degeneration: One-year results. Arch Ophthalmol (121) (2003) 667-673.
8. Jonas J. B.,Kreissing I.,Hugger P., Sauder G , S. Panda-Jonas, Degenring R., Intravitreal triamcinolone acetonide for exudative age-related macular degeneration, British Journal of Ophthalmology (87) (2003) 462-468.
9.Lazic R., Gabric N., Verteporfin therapy and intravitreal bevacizumab combined and alone in choroidal neovascularization due to age-related macular degeneration, Ophthalmology (114) ( 6) (2007) 1179-1185.
10. Munshi A. , Age related macular degeneration: A study of patients managed with radiotherapy, Journal of cancer research and therapeutics (3) (1) (2007) 12-16
11. Lewis H , Intraoperative fibrinolysis of submacular haemorrhage with tissue plasminogen activator and surgical drainage, American.Journal of Ophthalmology (118) (1994) 559-568.
12. Potter M., Improvement in macular function after translocation surgery in a patient with age-related macular degeneration, American Journal of Ophthalmology (129) ( 4) (2000) 547-549
13. Reichel E.,Berrocal A. M ,Desai V., Duker J.S. ,Pulfiafito C. A, Transpupillary thermotherapy of occult subfoveal choroidal neovascularization in patients with age related macular degeneration, Ophthalmology (106) (1999) 1908-1914.
14. http:// www.nutraingredients .com Europe 16/08/2006.
15. Debefve E., Combination therapy using aspirin-enhanced photodynamic selective drug delivery, Vascular Pharmacology (46) (3) (2007) 171-180.
16. Rosenfeld J. P, Systemic bevacizumab (Avastin) Therapy for neovascular age-related macular degeneration twenty-four-week results of an uncontrolled open-label clinical study, Ophthalmology (11 ) (113) (2006) 2002-2011.
17. Moshfeghi A.A ,Peyman G. A., Micro and nano particulates, Advanced Drug Delivery Reviews (57) (14) (2005) 2047-2052.
18. Nobuhiro N; Current state, achievements, and future prospects of polymeric micelles as nanocarriers for drug and gene delivery, Pharmacology and Therapeutics (112) (3) (2006) 630-648.
19. Fattal E. , Ocular delivery of nucleic acids: antisense oligonucleotides, aptamers and siRNA, Advanced Drug Delivery Reviews (58) (11) (2006) 1203-1223.
Friday, November 21, 2008
Angiogenesis Inhibitors
Lucentis® (Generic name: ranibizumab injection)
Year Approved by the FDA: 2006
Effective for: Wet macular degeneration
How it works: Lucentis®is an antibody fragment that binds to and inhibits the biologic activity of human Vascular Endothelial Growth Factor A (VEGF-A), a protein that is believed to play a critical role in the formation of the new abnormal and leaky blood vessels, characteristic of wet macular degeneration. The drug is injected into the vitreous portion of the eye (the clear jelly-like substance that fills the eye from the lens back to the retina). Due to the fact that the production of VEGF-A is ongoing, routine administration of this drug is required.
According to data collected during clinical trials, nearly 95 percent of the participants who received a monthly injection maintained their vision at 12 months following the beginning of treatment compared to approximately 60 percent of patients who received the control treatment. Approximately one-third of patients in these trials had improved vision at 12 months.
Most common side effects: The most commonly reported adverse events included hemorrhage of the conjunctiva (the membrane that covers the white part of the eye), floaters, eye pain, increased eye pressure, and inflammation of the eye. Serious adverse events such as endophthalmitis (severe inflammation of the interior of the eye), retinal detachment, retinal tear, increased eye pressure and traumatic cataract were rare and often related to the injection procedure. There is also a small increase in the risk of stroke. Clinical trial data indicated that approximately .3 percent of patients suffered a stroke when given a .3 milligram dose of Lucentis®compared to 1.2 percent of patients who received a .5 milligram dose. In addition, patients who have previously suffered a stroke may be at greater risk of having another stroke.
Potentia Pharmaceuticals' Drug Candidate for Age-Related Macular Degeneration Shows Positive Safety Profile in Phase I Clinical Trial
AMD Patients Treated with POT-4 Demonstrate No Adverse Toxic Effects
ATLANTA, Nov 10, 2008 /PRNewswire via COMTEX/ -- Potentia Pharmaceuticals, a privately held biotechnology company developing medicines for the treatment of age-related macular degeneration (AMD), presented Phase I data last week during the Retina Subspecialty Day at the American Academy of Ophthalmology (AAO) Annual Meeting in Atlanta, GA. The data was from the ASaP (Assessment of Safety of Intravitreal POT-4 Therapy for Patients with Neovascular Age-Related Macular Degeneration) clinical trial for the company's leading drug candidate, POT-4, which is being developed for the treatment of AMD.
The ASaP trial is a first-in-man, multi-center, single escalating dose study. The interim results of this trial revealed no drug-related toxicity based on clinical signs, ophthalmic examinations, or laboratory results at any time point monitored in patients treated with up to 150 microgram/dose of POT- 4. Additionally, no serious adverse events and no identifiable intraocular inflammation were reported.
Preliminary results indicate that intravitreal POT-4 is safe, and the data accumulated so far support the continued investigation of POT-4 for the treatment of both dry and wet AMD with larger randomized clinical trials to further define its efficacy profile.
"These safety data strongly support the further development of POT-4 as a potential treatment for patients with AMD," said Cedric Francois, President and CEO of Potentia Pharmaceuticals. "We believe that the product has significant promise based on these early-stage findings and look forward to further testing of the compound in higher doses as we continue this trial."
About POT-4
POT-4 is a complement inhibitor, which shuts down the complement activation cascade that could otherwise lead to local inflammation, tissue damage and upregulation of angiogenic factors such as vascular endothelial growth factor (VEGF) in the eye. Based on this mechanism of action, POT-4 holds the potential to be effective against both dry and wet AMD.
About AMD
AMD is the leading cause of blindness in the elderly of the western world and affects more than 10 million patients in the United States alone. The current standard of care for AMD relies primarily on angiogenesis inhibitors, an approach geared towards the approximately 10-15% of AMD patients with complications resulting from ocular angiogenesis (growth of new blood vessels and bleeding in the back of the eye). No drug currently on the market has been approved for the treatment of the remaining patients, who suffer from the so- called "dry" form of the disease.
About the Complement System and POT-4
Complement activation is an inflammatory process involving dozens of plasma proteins, ultimately leading to cell membrane disruption through the membrane attack complex (MAC). Activation of the complement system is an important part of the body's defensive immune response against pathogens such as bacteria and viruses. In spite of its defensive function, inappropriate or excessive complement activation can have destructive consequences if left unchecked. Over the past three years, multiple scientific publications have strongly linked variants of genes encoding components of the complement system with a predisposition toward AMD.
POT-4 binds tightly to complement component C3, preventing its participation in the complement activation cascade. As C3 is the central component of all major complement activation pathways, its inhibition effectively shuts down downstream complement activation that could otherwise lead to local inflammation, tissue damage and upregulation of angiogenic factors such as vascular endothelial growth factors (VEGF).
About Potentia
Potentia Pharmaceuticals, Inc. is an early stage biotechnology company focused on developing novel therapeutics and drug delivery technologies to address chronic inflammatory diseases, with an initial emphasis on diseases of the eye such as age-related macular degeneration.
Media Requests:
Paul Kidwell
(617) 296-3854
paulkidwell@comcast.net
Contact for Potentia Pharmaceuticals:
Pascal Deschatelets
(502) 569-1053
SOURCE Potentia Pharmaceuticals, Inc.
http://www.potentiapharma.comCopyright (C) 2008 PR Newswire. All rights reserved
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