QRX003
QRX003 is under development as a potential therapy for the treatment of Netherton Syndrome (NS). The product is a once-daily topical lotion comprised of a broad-spectrum serine protease inhibitor, formulated with the proprietary Invisicare® delivery technology.
Netherton Syndrome (NS)
Netherton Syndrome – a rare, hereditary skin disorder – is an autosomal recessive genetic disease caused by a mutation in the SPINK5 gene (serine protease inhibitor, Kazal Type 5) leading to severe skin barrier defects and recurring infections, as well as a pronounced predisposition to allergies, asthma and eczema. Patients also often suffer from severe dehydration, chronic skin inflammation and stunted growth.
The SPINK5 gene, when behaving normally, encodes a protein, called Lympho-Epithelial Kazal Type Related Inhibitor or LEKTI, that serves to regulate the activity of certain skin proteases, called Kallikreins, that are responsible for the normal everyday process of skin shedding. For patients with NS, the LEKTI protein is absent due to the mutation of the SPINK5 gene. The effect of this absence of the LEKTI protein is unregulated hyperactivity of the Kallikreins which in turn results in uncontrolled desquamation and leads to a highly porous and defective skin barrier.
People with Netherton Syndrome have too few layers of their outer skin (stratum corneum) so the skin does not perform its primary function as a protective barrier. This leads to the increased risk of infections, warts, skin cancer and irritation by allergens and other environmental microorganisms. The skin is prone to scaling and is accompanied by hair anomalies, along with increased susceptibility to atopic eczema. Pruritus (itching) is a major problem as well as elevated IgE antibody levels. Furthermore, because the skin is so compromised, patients experience trans-epidermal water loss (TEWL), and adults can lose up to 2 quarts of water a day. In infants and children, TEWL can result in a failure to thrive and delayed or stunted growth.
Currently, there is no cure for Netherton Syndrome, nor are there any approved therapeutic treatments. What is available, such as skin moisturizers, are currently limited to providing symptomatic relief. Due to the highly compromised skin, even the selection of an appropriate moisturizer can be challenging. For example, moisturizers typically used for skin barrier repair, such as those containing lanolin and petrolatum, can cause further skin damage to NS patients due to friction or high shear forces upon application or removal. Topical steroids may have harmful rather than helpful effects and can further reduce the thickness of the skin barrier. Incidences of Cushing’s Syndrome have also been reported from the use of topical steroids. Other standard topical treatments, such as calcineurin inhibitors, can lead to dangerously high systemic blood levels due to the defective skin barrier.
QRX003: Tailored Treatment
QRX003, a topical lotion, offers a combination of a broad-spectrum serine protease inhibitor formulated with the proprietary Invisicare® technology.
When applied daily to the skin, the active ingredient in QRX003 performs the function of the missing LEKTI protein and down regulates, but does not completely stop, the activity of the Kallikreins, leading to a more normalized skin shedding process and the formation of a stronger and more effective skin barrier. The serine protease inhibitor in QRX003 also acts as a potent anti-inflammatory and antioxidant. The Invisicare® delivery technology offers immediate protection against TEWL and environmental agents. Uniquely this technology both moisturizes the skin while providing a protective barrier.
In addition to Netherton Syndrome, QRX003 is being developed for the following additional rare disease indications:
Peeling Skin Syndrome
Due to mutations in the TGM5 gene, inherited in an autosomal recessive pattern, this disorder is characterized by the continuous painless peeling of the top layer of skin. It can appear as abnormal blistering of the skin anywhere on the body, but most often presents on the hands and feet. Symptoms can include pruritus (itching), hyperpigmentation, and redness. Incidence is less than one in one million.
SAM Syndrome
Presents with severe skin dermatitis, multiple allergies and metabolic wasting (SAM). This is a rare life-threatening inherited condition caused by mutations in the desmoglein1 gene.
Palmoplantar Keratoderma
This condition causes thickening of the skin on the hands and feet and can be either inherited or acquired. Patients may experience pain when walking, excessive foot odor and/or sweating, along with reduced sensation of fingers or toes. Incidence is 4.4 cases per 100,000.