DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for pemphigus — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePemphigus maps to a 4-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for pemphigus is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
Bruton tyrosine kinase (BTK) — BTK is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 7h-pyrrolo[2,3-d]pyrimidin-4-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6VXQ · 1.4 Å · ligand N-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]methyl}benzamide (RQS). Experimental structure, not a prediction.
What the evidence adds up to
Twenty-two newly diagnosed pemphigus patients were randomised to high-dose prednisolone (120 mg/day) or low-dose (60 mg/day) and followed for five years. Rapid initial control appeared better with the high-dose regimen, but no long-term benefit was seen in relapse frequency or complication rates. In a separate series of 26 patients treated with intramuscular gold over ten years, gold was effective in 62% as primary treatment or as a steroid-sparing agent. An average of three months of therapy was needed before the daily prednisone dose could be halved. Four patients stopped all therapy and remained disease-free at study end. Toxic effects occurred in 42% of patients but resolved when gold was stopped. The authors note gold has a delayed onset, so patients usually still need systemic steroids when starting therapy, and they call for controlled prospective trials.
A five-year analysis of 123 patients treated with dexamethasone cyclophosphamide pulse (DCP) therapy, with modifications including additional daily oral betamethasone, systemic antibiotics for skin lesions, and oral anti-candida drugs for oral ulcers, reported that all patients were in complete remission at the time of analysis. The confirmed disease-free follow-up was more than five years in 62 patients, three to five years in 41, two to three years in three, and less than two years in six. Relapse rates were 7.7% in DCP patients and 15% in those receiving only dexamethasone pulses. Twenty-one patients with pemphigus refractory to prednisolone and azathioprine or mycophenolate mofetil were treated with pulsed intravenous methylprednisolone and cyclophosphamide (PPC). Seven had an excellent response, two a good response, five a moderate response, six a minimal response, and one no clinical response. Four achieved complete clinical remission after 11 to 22 pulses. The median prednisolone dose fell from 40 mg before pulsing to 10 mg at the last pulse, a median reduction of 66%. Adverse effects included transient lymphopenia in 12 patients, nonlife-threatening sepsis in seven, and premature ovarian failure in two.
A review article notes that pemphigus treatment is mostly art rather than science because the disease is rare, its severity and response vary greatly, and multiple therapies have rarely been evaluated in randomised trials. Systemic corticosteroids are the most effective and rapidly acting treatment, but high and prolonged doses cause serious side-effects. Adjuvant therapies are divided into rapidly acting ones—megadose intravenous steroids, plasmapheresis, and intravenous immunoglobulin (IVIg)—and slowly acting ones such as cyclophosphamide, azathioprine, cyclosporin, methotrexate, mycophenolates, gold, dapsone, antimalarials, and antibiotics. IVIg is considered probably safer than megadose steroids or plasmapheresis and as effective, but very costly. The author states that methotrexate in the dose range used for psoriasis is a personal preference, but warns against combining it with high-dose prednisone because of increased infection risk. The review emphasises that the goal is complete remission allowing all therapy to be discontinued, and that treatment should be divided into control, consolidation, and maintenance phases.
What is still missing are randomised controlled trials that compare the relative effectiveness of the many adjuvant therapies used in pemphigus. The evidence base consists of small case series and expert opinion. No trial has established whether more intensive initial therapy or longer consolidation reduces long-term relapse rates. Patient stratification by disease severity, autoantibody profile, or genetic background has not been prospectively tested. Funding for multicentre trials in this rare disease remains inadequate.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
International Journal of Dermatology · 1990 · 101 citations
Pemphigus Therapy with Oral Prednisolone Regimens A 5‐Year Study
AbstractTwenty-two newly diagnosed patients with pemphigus were randomly divided into two groups of 11 each. One group was placed on a high-dose prednisolone (120 mg/day) therapy and the other group on a low-dose (60 mg/day) therapy. The patients were followed for 5 years. Although a rapid initial control of the pemphigus appeared to be achieved with the high-dose regimen, this regimen did not have any long-term benefit over the low-dose regimen with respect to the frequency of relapse or in the incidence of complications.
AbstractBACKGROUND: Although gold has been reported to be useful in treating pemphigus vulgaris, its use has waned in recent years because of concerns regarding efficacy and toxicity. OBJECTIVE: To review 26 patients with pemphigus who were treated with intramuscular gold over a 10-year period. RESULTS: Gold was effective in 62% of patients as a primary treatment for pemphigus or as a steroid-sparing agent. An average of 3 months of therapy was required before the daily prednisone dosage could be halved. Four patients were free of disease and stopped receiving all therapy at the conclusion of the study. Toxic effects due to gold therapy developed in 42% of patients and all adverse effects resolved with its cessation. CONCLUSIONS: While toxic effects limit the use of gold in many patients with pemphigus, it may be effective in treating a large percentage of patients who otherwise are unable to reduce their steroid requirement. Because of its delayed onset of action, patients treated with gold usually require systemic steroids when therapy is initiated. Controlled, prospective trials are needed to further evaluate the efficacy of gold and its potential steroid-sparing effects.
Indian Journal of Dermatology Venereology and Leprology · 2008 · 33 citations · open access
Current regimen of pulse therapy for pemphigus: Minor modifications, improved results
AbstractBACKGROUND: If administered properly, dexamethasone cyclophosphamide pulse (DCP) therapy has the potential to effect lifelong recovery from pemphigus. AIMS: The objective of this paper is to highlight various parameters of DCP therapy and also, to report the effects of a few modifications in the regimen. METHODS: An analysis of 123 patients treated with the DCP/DP regimen over a period of five years (1998 to 2002) is presented here. Seventeen patients who did not start/continue the treatment and three patients who died during the treatment have been excluded from the analysis. Twenty patients who had not yet started families were given only dexamethasone pulses (DPs) while 103 patients received DCPs. Low dose (50 mg/day) cyclophosphamide was used as in the standard regimen. The three modifications introduced into the regimen were: (1) an additional daily dose of oral betamethasone sufficient to control the disease activity during phase I, which was progressively tapered off completely as the patient recovered, (2) use of systemic antibiotics if the patient had skin lesions, and oral anti-candida drugs if the patient had oral ulcers until complete healing, and (3) insistence on thorough cleaning of the skin and scalp with a normal soap and shampoo, and proper maintenance of oral hygiene in spite of skin/mucosal lesions. The regimen consisted of DCP/DP repeated in exactly 28-day cycles, along with 50 mg cyclophosphamide per day, insistence on completing the treatment and avoiding irregular pulses in all patients. The number of DCPs/DPs during phase I varied in different patients depending upon the dose of betamethasone used and the rate of recovery, but phase II (nine DCPs/DPs in exactly 28-day cycles along with 50 mg cyclophosphamide per day) and phase III (only 50 mg cyclophosphamide per day) was fixed at nine months each. This was followed by posttreatment follow-up (phase IV). RESULTS: At present, all the patients are in complete remission. The confirmed period of posttreatment, disease-free follow-up period has already been more than five years in 62 patients, 3-5 years in 41 patients, 2-3 years in three patients and less than two years in six patients. Eight DCP patients and three DP patients developed a relapse (the relapse rates thus being 7.7 and 15% respectively) and received a second course of pulse therapy. They are also in remission at present. The duration of phase I was three months in 62 patients, 4-5 months in 28 patients, 6-9 months in 13, 10-12 months in nine patients and more than 12 months in 11 patients. The maximum daily dose of betamethasone used in these patients was nil in 17 patients, 1-2 mg in 85, 3-4 mg in 16, and> 4 mg in five patients. CONCLUSIONS: The modifications employed in this study could ensure the cure of all pemphigus patients by using DCP therapy administered at a private clinic.
British Journal of Dermatology · 2009 · 33 citations
Pulsed intravenous cyclophosphamide and methylprednisolone therapy in refractory pemphigus
AbstractBACKGROUND: Pemphigus is a rare autoimmune blistering disorder. The mainstay of current treatment is high-dose oral corticosteroid therapy in combination with a steroid-sparing agent. Adjuvant therapy is important for disease control and to reduce the iatrogenic effects of oral prednisolone. Pulsed therapy with intravenous methylprednisolone and cyclophosphamide (PPC) has been shown to be an effective treatment but there are currently few data on its use in patients who have failed to respond to conventional immunosuppression. OBJECTIVES: To report the clinical and immunological responses of 21 patients with pemphigus refractory to prednisolone and azathioprine or mycophenolate mofetil treated in our department with a standard protocol of monthly PPC. METHODS: Patients with pemphigus were identified who had undergone PPC therapy during the period between 1997 and 2006. Initial clinical severity and response to treatment was assessed. In addition, change in intercellular antibody titres and desmoglein 1 and 3 antibodies to PPC therapy was also recorded. RESULTS: Of the 21 patients treated, seven had an excellent response, two a good response, five a moderate response, six a minimal response and one patient had no clinical response. Four patients achieved complete clinical remission and the number of pulses for these patients varied between 11 and 22. We observed significant reductions in indirect immunofluorescence titres for normal human skin substrate (P = 0.0078) and antidesmoglein 1 and 3 autoantibody levels (P = 0.007 and P = 0.0085, respectively) from pre-PPC therapy to 1 year after the last pulse. All patients were able to reduce their prednisolone dose from a pre-pulsing median dose of 40-10 mg at the last pulse with a median dose reduction of 66% (P < 0.001). The most common adverse effect was transient lymphopenia (12 patients); nonlife-threatening sepsis (seven patients) and premature ovarian failure (two patients) also occurred. CONCLUSIONS: PPC can be an effective treatment for refractory pemphigus but its adverse effects should be considered prior to therapy and closely monitored in patients on treatment.
Journal of the European Academy of Dermatology and Venereology · 2002 · 8 citations
How should pemphigus be treated?
AbstractThe general principles of treating pemphigus are well accepted.1 The practical application of these principles into the day-to-day management of individual patients is, however, more controversial. The reasons are that pemphigus is a rare disease, its severity and response to therapy vary greatly from patient to patient, and while multiple therapies are available they have rarely been evaluated scientifically in randomized trials. Hence, the effectiveness of many of the treatments that are used is uncertain, and their relative effectiveness is mostly unknown apart for that of systemic steroids, which clearly work. For these reasons, much of the treatment of pemphigus is ‘art’ rather than ‘science’, and subject to personal bias. The goal of treatment is to induce a complete remission that permits all therapy to be discontinued, and to do so in a manner that minimizes side-effects. Treatment is divided into three phases, based on the activity of the disease: A control phase, in which the intensity of therapy is rapidly escalated until a level is reached that suppresses disease activity as evidenced by a marked reduction or complete suppression of new lesion formation, absence of itching, and beginning healing of established lesions. The importance of treating the disease vigorously enough to suppress disease activity cannot be overemphasized, because if this is not achieved it is unlikely that one can successfully taper treatment. The length of this period is weeks, not months. Pemphigus responds rapidly to therapy (within days) in most cases if the right dose of medication is used, so that continued disease activity is an indication of inadequate treatment. A consolidation phase, during which the type and dose of medication(s) required to control disease activity, is maintained until the bulk of lesions has healed. The length of this period is also measured in weeks not months. If lesions are slow to heal, it is an indication that the intensity of therapy is inadequate and should be increased. Therapy should not be tapered until the bulk of lesions is healed, to minimize subsequent flares in disease activity. A maintenance phase, during which medications are gradually tapered to the lowest level that suppresses the appearance of new lesions, with the goal being to discontinue eventually all medications. This can ultimately be achieved in the majority of patients.2 A major unanswered question is whether flares in disease activity can be minimized by more intensive and/or longer therapy during the control and/or consolidation phase of treatment and/or by using adjuvant therapies. The most effective and rapidly acting treatment for pemphigus are systemic corticosteroids. Unfortunately, the high and prolonged doses of this medication that may be required to treat the disease can be associated with serious side-effects. Hence there is a continued search for alternate or ‘adjuvant’ treatments that can be used to replace or reduce the need for steroids. The problem is that while many adjuvant therapies are available, objective data on their effectiveness in the form of randomized trials are mostly lacking. Adjuvant therapies can be divided into two categories based on the speed of their effect: (i) rapidly acting, which are normally used to control active disease unresponsive to systemic steroids, and (ii) slowly acting, which are normally used during the maintenance and/or consolidation phases of treatment to reduce the need for steroids. The effectiveness of rapidly acting therapies is easier to evaluate in the absence of randomized trials as their effect can be seen within days to a few weeks, making it easier to link clinical improvement to use of the new therapy. Therapies that act rapidly include pulse therapy with megadoses of steroids given intravenously and plasmapheresis. Both can control disease activity within a week or two, but neither is effective in all patients. Which procedure is better than the other is not known, and both can be associated with severe side-effects. Whether either treatment improves long-term outcome is not known. While both procedures speed entry into the consolidation phase of treatment, neither removes the need for prolonged maintenance therapy. The latest approach to control disease activity rapidly is the intravenous administration of high doses of immunoglobulin (IVIg). This can also control within 1 or 2 weeks, disease activity unresponsive to high doses of systemic steroids in many, but not all, patients. Patients who do not respond to one cycle of treatment may respond to a second or third cycle. The major advantage of IVIg over megadose intravenous steroids or plasmapheresis is that it is probably safer and as effective. The major disadvantage is that it is very costly. Because of its safety advantage, this is currently our favoured procedure to control active pemphigus unresponsive to high doses of steroids or when the dose cannot be increased because of intolerance or side-effects. In patients with unresponsive active disease, superinfection of skin lesions with bacterial, fungal (candida) or viral (herpes simplex) organisms must always be excluded. Adjuvant therapies with a slow onset of action include a variety of drugs that are cytotoxic or immunosuppressive, such as cyclophosphamide (Cytoxan), azathioprine (Imuran), cyclosporin, methotrexate, mycophenolates (CellCept) and anti-inflammatory drugs such as gold, dapsone, antimalarials and certain antibiotics. These agents are not reliably effective by themselves, so that all are usually used in conjunction with systemic steroids. Because of the lack of hard data regarding the relative effectiveness of these drugs, the choice of a particular agent should be based on the physician's experience with the drug and the patient's underlying medical condition(s), which may make the side-effect profile of one agent more desirable than that of another. As an example, chronic use of some immunosuppressive agents, in particular cyclophosphamide, is associated with loss of fertility and an increased risk of cancer, so that it is reasonable to attempt to avoid these drugs in younger patients in their reproductive years. My personal current preference is methotrexate, in the dose range used to treat psoriasis. An important proviso is that methotrexate should not be used in patients concurrently receiving high doses (more than 60 mg/d) prednisone, as this combination appears to increase the chances of infections. A number of other concerns must be addressed in the treatment of pemphigus. These include: (i) confirming the diagnosis by review of the clinical, histological and immunological findings; (ii) appropriate baseline medical evaluation with a focus on underlying conditions that might increase risk of side-effects to steroids or other therapies (these should include chest X-ray, bone density studies, ophthalmological examination and tuberculin skin tests); (iii) ENT examination to evaluate oesophageal or nasal symptoms, which are much more common than usually appreciated; (iv) topical therapy to keep lesions clean and to reduce pain; (v) intralesional steroids to speed the healing of individual lesions; (vi) minimizing potential side-effects of therapy by using agents that can reduce osteoporosis, using antacids, encouraging exercise, following a diet low in sugar and salt; and (vii) minimizing dental procedures, sun exposure and radiation therapy, which all can cause a flare in disease activity. Lastly, it is important that patients be followed frequently particularly when doses of medications are being increased or decreased, as pemphigus is a dynamic disease that responds rapidly to changes in therapy.
Journal of Dermatological Case Reports · 2014 · 8 citations · open access
Pemphigus vulgaris localized to the tongue
AbstractBACKGROUND: Pemphigus vulgaris is an autoimmune blistering disease that may initially present as localized lesions. It rarely remains localized throughout its clinical course. OBSERVATIONS: A 53-year-old woman with non-progressive pemphigus vulgaris localized to the tongue for 18 years is presented. Clinical examination showed erosions and ulcerations limited to the lateral margins of the tongue. Patient was treated with sublesional triamcinolone-acetonide injections as lesions recurred. Finally, triamcinolone- acetonide injections at three weeks intervals for three months induced a longterm sustained clinical remission for 18 months. The indirect immunofluorescence did not correlate with disease activity. Anti-desmoglein 3 antibodies (ELISA) remained elevated throughout the clinical course and during remission. CONCLUSIONS: This case highlights the recognition of localized pemphigus vulgaris and demonstrates the importance of local therapy and its potential to induce longterm remission. Similar report of additional cases may create a standard of care for non-progressive, localized pemphigus.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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