Thursday, April 06, 2006
More on topical (calcium) dobesilate as a potential rosacea treatment
I blogged about topical application calcium dobesilate and rosacea in November 2005, when this study was published, and said I would write more (but didn't). This week, I received an email from a blog reader who has had experience with using this as a topical with interesting results, so I thought I would revisit!
To recap on the original study, "Theraputic Response of Rosacea to Dobesilate" (emphasis mine):
Despite an incomplete understanding of the pathogenesis of rosacea, therapeutic modalities continue to expand. The principal subtype of rosacea includes erythematotelangiestatic rosacea, which is characterized by uncontrolled angiogenesis. Angiogenic growth factors such as fibroblast growth factors (FGF) and vascular endothelial growth factor (VEGF) are currently targets of intense effort to inhibit deregulated blood vessel formation in diseases such as cancer. Here we report a 33-years-old woman with erythematotelangestatic rosacea who responds to a daily treatment of topically applied dobesilate, an inhibitor of FGF, with an improvement in erythema and telangectasia after two weeks. Thus, dobesilate might be useful in the treatment of rosacea and other diseases that depend on pathologic angiogenesis.
[frustratingly the full paper does not appear to be available anywhere online for purchase – if you spot it please drop me a line at rosacea.co.uk]
What is dobesilate used for?
Calcium dobesilate is administered orally as a treatment for diabetic retinopathy. The drug is called “Doxium" and is available in tablet or capsule form. Further info here, and here.
It is believed to have the following effects when taken orally, which may have implications for rosacea:
1. Potent antioxidant, “Doxium may also preserve vascular endothelial function by acting directly as antioxidant to protect lipids from peroxidation” (source)
2. Reduces microvascular permeability, as measured by “vitreous fluorophotometry, retinal haemorrhages, skin capillary resistance, blood albumin leakage, blood viscosity” (source)
3. It is an angiogenesis inhibitor, “According to the results reported here, dobesilate remarkably reduced vessel ingrowth in aFGF-containing subcutaneous sponges in mice”. One of the investiagors in this study, “Cuevas P” (Pedro Cuevas) was the author of the rosacea paper. (source) (full paper is online)
Are there any examples of topical usage other than the one rosacea study?
Yes! Again, Pedro Cuevas has studied the effect of “Dobesilate in the treatment of plaque psoriasis” (full paper is online), where the abstract reports (emphasis mine):
"Fibroblast growth factor (FGF)-mediated pathways participate in many of the cellular events implicated in the pathogenesis of psoriasis. Thus, targeting FGF signals may be potentially therapeutic in the treatment of psoriasis. We report for the first time on a 43-year-old man with chronic-type plaque psoriasis with a daily topical treatment of dobesilate, a new FGF inhibitor. As early as at day 14, the patient had cleared or achieved excellent improvement of psoriatic skin lesions. Topical dobesilate offers the potential for treatment of plaque psoriasis without atrophy or other local side effects associated with the use of topical corticosteroids.”
I found a copy of the full psoriasis paper as PDF, here.
The photos are impressive and show near complete resolution (cure?) of the psoriasis. The topical used was described as follows:
“Lesions were treated with potassium dobesilate [hydroquinone monosulfonic acid potassium salt (Merck) (5 percent in a cream formulation, applied twice daily by the patient himself)]”
Interestingly, the paper describes that “after 2 weeks of treatment, the patient had almost completed clinical resolution of the lesions with no recurrence after two months of treatment withdrawal. No adverse events were observed”
Pedro Cuevas MD has a long history of studying angiogenesis and anti-angiogenesis, with hundreds of published papers. Here is more information.
Calcium dobesilate has also been investigated for topical treatment of hemorrhoids, in a study "Effectiveness and innocuousness of the association of calcium dobesilate, dexamethasone acetate and lidocaine versus prednisolone capronate with dibucaine clorohydrate in the treatment of hemorrhoids", with positive results.
[update]
Via the the rosacea news site's article on this paper, I also came across this case study, again by Pedro Cuevas MD, where topical dobesilate was used to treat basal cell carinoma topically. I quote: "a nodular BCC on the face of a 62 year old man was treated with calcium dobesilate (2.5% in a suspension forumulation, applied twice daily by the patient) for 4 weeks. After 4 weeks there was nearly complete clinical resolution of the disease..."
In summary
I think this will be an interesting one to follow. Hopefully more trials of this potentially promosing drug can be performed.
To recap on the original study, "Theraputic Response of Rosacea to Dobesilate" (emphasis mine):
Despite an incomplete understanding of the pathogenesis of rosacea, therapeutic modalities continue to expand. The principal subtype of rosacea includes erythematotelangiestatic rosacea, which is characterized by uncontrolled angiogenesis. Angiogenic growth factors such as fibroblast growth factors (FGF) and vascular endothelial growth factor (VEGF) are currently targets of intense effort to inhibit deregulated blood vessel formation in diseases such as cancer. Here we report a 33-years-old woman with erythematotelangestatic rosacea who responds to a daily treatment of topically applied dobesilate, an inhibitor of FGF, with an improvement in erythema and telangectasia after two weeks. Thus, dobesilate might be useful in the treatment of rosacea and other diseases that depend on pathologic angiogenesis.
[frustratingly the full paper does not appear to be available anywhere online for purchase – if you spot it please drop me a line at rosacea.co.uk]
What is dobesilate used for?
Calcium dobesilate is administered orally as a treatment for diabetic retinopathy. The drug is called “Doxium" and is available in tablet or capsule form. Further info here, and here.
It is believed to have the following effects when taken orally, which may have implications for rosacea:
1. Potent antioxidant, “Doxium may also preserve vascular endothelial function by acting directly as antioxidant to protect lipids from peroxidation” (source)
2. Reduces microvascular permeability, as measured by “vitreous fluorophotometry, retinal haemorrhages, skin capillary resistance, blood albumin leakage, blood viscosity” (source)
3. It is an angiogenesis inhibitor, “According to the results reported here, dobesilate remarkably reduced vessel ingrowth in aFGF-containing subcutaneous sponges in mice”. One of the investiagors in this study, “Cuevas P” (Pedro Cuevas) was the author of the rosacea paper. (source) (full paper is online)
Are there any examples of topical usage other than the one rosacea study?
Yes! Again, Pedro Cuevas has studied the effect of “Dobesilate in the treatment of plaque psoriasis” (full paper is online), where the abstract reports (emphasis mine):
"Fibroblast growth factor (FGF)-mediated pathways participate in many of the cellular events implicated in the pathogenesis of psoriasis. Thus, targeting FGF signals may be potentially therapeutic in the treatment of psoriasis. We report for the first time on a 43-year-old man with chronic-type plaque psoriasis with a daily topical treatment of dobesilate, a new FGF inhibitor. As early as at day 14, the patient had cleared or achieved excellent improvement of psoriatic skin lesions. Topical dobesilate offers the potential for treatment of plaque psoriasis without atrophy or other local side effects associated with the use of topical corticosteroids.”
I found a copy of the full psoriasis paper as PDF, here.
The photos are impressive and show near complete resolution (cure?) of the psoriasis. The topical used was described as follows:
“Lesions were treated with potassium dobesilate [hydroquinone monosulfonic acid potassium salt (Merck) (5 percent in a cream formulation, applied twice daily by the patient himself)]”
Interestingly, the paper describes that “after 2 weeks of treatment, the patient had almost completed clinical resolution of the lesions with no recurrence after two months of treatment withdrawal. No adverse events were observed”
Pedro Cuevas MD has a long history of studying angiogenesis and anti-angiogenesis, with hundreds of published papers. Here is more information.
Calcium dobesilate has also been investigated for topical treatment of hemorrhoids, in a study "Effectiveness and innocuousness of the association of calcium dobesilate, dexamethasone acetate and lidocaine versus prednisolone capronate with dibucaine clorohydrate in the treatment of hemorrhoids", with positive results.
[update]
Via the the rosacea news site's article on this paper, I also came across this case study, again by Pedro Cuevas MD, where topical dobesilate was used to treat basal cell carinoma topically. I quote: "a nodular BCC on the face of a 62 year old man was treated with calcium dobesilate (2.5% in a suspension forumulation, applied twice daily by the patient) for 4 weeks. After 4 weeks there was nearly complete clinical resolution of the disease..."
In summary
I think this will be an interesting one to follow. Hopefully more trials of this potentially promosing drug can be performed.
