Companies working in the psoriasis area: Leo Pharma
Introduction/Definitions:
Psoriasis, an autoimmune disorder, is a chronic skin condition. It is characterized by inflamed, red, raised areas that often develop into silvery scales on the scalp, elbows, knees, and lower back. Psoriasis can also be associated with arthritis. It is estimated to affect 7.5 million people in the U.S.
Psoriasis is a chronic recurrent inflammatory autoimmune pathology with a significant genetic component and several interferences of immune cells and their cytokines. It has a worldwide prevalence of about 2-3% of the general population, with variabilities depending on the skin phenotype, and it is lower in Asia or Africa and higher among Scandinavian populations. See Vreju
Age of onset of psoriasis is bimodal with peaks at 30-39 and 60-69 for men, and ten years earlier for women.
Plaque psoriasis: Psoriases affects the rate that skin cells regenerate. The most common form of soriasis is plaque psoriasis, which causes flaky, scaly patches (Plaques) to form on the skin.
Patches are common on the elbows, knees, scalp and lwoer back but can occur anywhere on the body.
Psoriatic arthritis: Psoriasis leads to psoriatic arthritis, a painful swelling of joints, in up to 30% of cases.
Symptoms/Pathogensis:
Psoriasis is a chronic disease which has fare-ups. Severity can vary between episodes and people -from small patches to alrge areas of skin, which may be itchy and sore.
Other diseases such as obesity, CVD, liver disease, diabetes and metabolic syndrome are more common among Pshoriasis sufferers (suspected shared genetic factors).
Genetic Basis: Approximately one-third of psoriasis’s genetic impact on psoriasis development is associated with the MHC region, with genetic loci located on chromosome 6. The most eloquent genetic factor of psoriasis, PSORS1, was identified in the MHC I site, where human leukocyte antigen (HLA)-Cw-6 was considered the PSORS1 risk variant. PSORS1 lies within the scope of a 300 kb critical region in the MHC, where research studies have identified about fifteen genes strongly related to psoriasis. The recorded data indicate that the HLA-C is the most likely PSORS1 gene. The risk allele HLACw0602*, present in up to 10-15% of the general population, inputs a 20-fold higher risk for developing psoriasis and is proven to be present in about 60% of psoriasis patients. It has been identified predominantly in young subjects with a familial history of psoriasis, where various infections, predominantly Streptococcal ones, trigger the first lesions. Moreover, subjects with homozygous HLA-Cw0602* allele manifested a five times higher psoriasis risk than heterozygous ones. PSORS4 resides on chromosome 1q21, and it has been associated with the presence of LCE genes (late cornified envelope genes), as the deletion of LCE3B and LCE3C is highly related to psoriasis. The expression of this protein is significantly increased in psoriatic lesions. See Vreju
Microbiome:
Multiple studies have reported changes in the skin microbiome for different pathologies, including psoriasis, and the analysis of specimens from both lesions and regular areas, along with probes from controls, have enlightened the essential data. In 2008, Gao et al. reported that Firmicutes was the most plentiful phylum populating psoriatic skin and Actinobacteria in unaltered samples from psoriasis patients and healthy individuals. A study published by Fahlén et al. revealed that there were three significant microorganisms present both in normal and psoriatic skin, Firmicutes, Proteobacteria, and Actinobacteria, as well as a significantly higher level of Proteobacteria in psoriasis compared to controls. Another important observation of the report indicates the lower level of Staphylococci and Propionibacteria in psoriasis patients compared to healthy individuals. See Vreju
Disruptions in the gut microbiome may also promote an increased risk of metabolic and autoimmune conditions, with the potential to initiate or sustain an inflammatory status, including psoriasis and its well-described comorbidities. The gut microbiome integrates an extensive number of bacterial types, represented mainly by Actynobacteria, Bacterioides, Firmicutes, Fusobacteria, Proteobacteria, and Verrucomicrobia, as well as viruses, fungi, protozoa, or Archaea, maintaining a symbiotic status with the host highly influenced by age, genetics, dietary manners, and environmental, external factors. Changes in the local intestinal microbiome can interact with skin homeostasis by influencing systemic immunomodulatory mechanisms. Several reports have concluded that the changes seen in patients with psoriasis are relatively similar to those identified in patients with inflammatory bowel diseases, with an exuberance of Actinobacteria and Firmicutes, conjunctively to the Firmicutes-to-Bacteroides ratio, representing the model of the altered gut epithelial barrier. See Vreju
Karatinocytes: Psoriasis is a pathology characterized by hyperproliferation and the disturbed differentiation of KCs, cells with both structural and immune roles that interfere in the early stages of the disease and support the maintenance of chronic inflammation. They constitute the main cellular population altered in psoriasis, as they express receptors for all types of cytokines involved in the complex pathogenesis of the disease. See Vreju
Dendritic Cells: Several types of DCs (plasmacytoid DCs (pDCs), conventional DCs (cDCs), and Langerhans cells (LCs)) are involved in the pathogenesis of psoriasis, with numerous reports demonstrating the presence of pDCs and cDCs in the lesional skin samples of these patients. Consecutive to different external stimulus, DCs activate and commute to professional antigen-presenting cells (APCs), with subsequent interaction with naive T cells and production of pro-inflammatory cytokines, TNF-α, IL-23, IL-12, and IL-6 that furthermore activate an inflammatory reaction, keratinocyte proliferation, and recruitment of neutrophils. A subset of inflammatory DCs, TIP-DCs, secrete TNF and inducible nitric oxide synthase (iNOS) with a pro-inflammatory response in patients with psoriasis. See Vreju
Treatment:
Steroid creams: One of the first-line treatment for psoriasis are steroid creams, which reduces inflammation. Steroid creams are typically applied for up to 4 weeks.
TNF-alpha inhibitors:
Humira (adalimumab) demonstrated that in patients with moderate to severe chronic plaque psoriasis, adalimuamb acheived statically significant results after 12 weeks.
Vitamin D and corticosteroid: has been used for the treatment of psoriasis. Leo Pharma (6,753,013) discloses a composition comprising at least one vitamin D or vitamin D analogus and at least one corticosteroid for topical application which is storage stable sold under the brand name Taclonex® which is FDA approved
PDE4 Inhibitors:
Otezla® is a phosphodiesterase-4 (“PDE4”) inhibitor marked by Amgen which is used for treating psoriasis and related conditions.
Tyrosine Kinase 2 inhibitors:
Sotyktu (deucravacitinib -Bristol Myers): is an oral, selective, allosteric tyrosine kinase 2 inhibitor for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
Related Diseases:
Palmoplantar pustulosis is related to psoriasis. Palmoplantar pustulosis, also known as palmoplantar pustular psoriasis, is a specific type of psoriasis that primarily affects the palms of the hands and the soles of the feet, characterized by the presence of pus-filled blisters. Psoriasis, in contrast, is a broader autoimmune condition that can affect various parts of the body, including the palms and soles, but is not limited to pustules.
–treatment:
–—PEDE4 inhibitors:
——Otezla (Amgen): is a small molecule that inhibits PDE4. It is being investigated in phase 3 studies for the treatment of palmoplantar pustulosis.