Epidermolytic Ichthyosis* (EI)
Cause EI is an autosomal dominant genetic disorder (where one bad gene causes the disease) with mutations in KRT1 or KRT10 genes.3 These genes are responsible for the production of keratin 1 and 10 which pair together and form filaments that provide shape and structural support for the epidermis (upper layer of the skin).
Unlike other skin blistering disorders, EI mutations often occur spontaneously post fertilization and express as somatic mosaicism.4–6 This means genetic mutations occur in some but not all of the cells in the body and severity of the disease depends on the percentage of cells affected. Hence, EI presents in limited areas of the skin with varying degrees of blistering and scaling (hyperkeratotic lesions). Children born with EI have red, blistering skin with areas of denuded (loss of epidermis) or thickened skin. With age, blistering decreases and scaling and thickening of the skin increases. Scaling and thickening of the skin on the hands and feet (palmoplantar keratoderma) can become severe, limiting mobility and hand dexterity. Extreme cases may require surgical intervention. Skin infections and heat intolerance are also common concerns.7
There is currently no cure for EI and symptomatic therapies such as keratolytics (therapeutics which soften the epidermis) and retinoids (used to strengthen skin) are challenging to implement. De-scaling of the skin with topical keratolytics or oral retinoids often removes too much scale (epidermis), resulting in raw exposed dermis.8 Bathing with salt or sodium bicarbonate is less effective than keratolytics but may help reduce palmoplantar keratoderma. Oral retinoids can cause kidney and liver toxicity and must also be closely monitored by a physician.9 The raw skin left from de-scaling is also difficult to treat and “barrier repair formulas” containing combinations of ceramides, cholesterol, petroleum, or lanolin can help protect the raw exposed skin.10 Various topical and systemic antibiotics are used to fight skin infections. Bathing with antiseptics or a diluted bleach solution can often help manage skin bacteria.11 EI represents a significant unmet medical need in dermatology. BioMendics is currently evaluating its Clearizome™ Technology to help remove mutated keratin 1 and 10 from EI affected cells to reduce blistering and scaling of the skin to improve the lives of patients living with EI.
*Prior to a 2009 consensus7 epidermolytic ichthyosis was referred to as bullous congenital ichthyosiform erythroderma or epidermolytic hyperkeratosis.
Pachyonychia Congenita (PC)
PC is caused by an autosomal dominant mutation (where one bad gene causes the disease) in one of a series of keratin genes (KRT6A, KRT6B, KRT6C, KRT16, and KRT17) with 30-40% of new diagnoses caused by a spontaneous mutation without family history.12 These genes are responsible for the production of keratin 6, 16, and 17 which pair together and form filaments that provide shape and structural support for the epidermis (upper layer of the skin).
PC manifests at birth with blisters, calluses, deformed, thickened, or discolored nails and by age 10 patients experience constant plantar pain (pain on the bottoms of the feet).12 The cause of this plantar pain is still unknown but has the most significant impact on quality of life and many patients rely on mobility aids such as crutches, canes, or wheelchairs.13 Additional symptoms of PC include oral leukokeratosis (mouth plaques/erosions), cysts, follicular hyperkeratosis, palmoplantar hyperhidrosis, and occasionally natal teeth.12,14 Cysts can also be a dominant feature presenting as milia (small white cysts) in infancy and transitioning to body cysts starting around puberty and continuing into adulthood. 14,15
No cure or effective treatment for PC is currently available. Patients manage plantar keratoderma and thickened nails by various methods of exfoliation (e.g., filing or grinding).16,17 Cysts often need to be drained and if they become infected or very painful may need surgical intervention. Constant plantar pain requires managed pain relief medication.16
PC represents a significant unmet medical need within the rare disease community. BioMendics is currently evaluating its Clearizome Technology to help remove mutated keratin 6, 16, and 17 from PC affected cells to reduce blistering and scaling of the skin to improve the lives of patients living with PC.
Systemic Sclerosis (SSc) or Scleroderma*
SSc is an autoimmune disorder where the immune system attacks the connective tissue under the skin and around internal organs and blood vessels. These injuries trigger an overproduction of collagen which causes the skin to thicken, making it hard, rigid, and painful. 19,20
The term scleroderma which means hardened skin, is caused by these collagen deposits. Skin thickening commonly occurs on the upper arms, lower legs, face, chest, and abdomen and may cause loss of flexibility in the joints (especially hands and fingers). Deposits over facial muscles can reduce facial movements and may even limit the range of mouth opening, requiring surgical intervention. 19,20
Scleroderma is often called systemic sclerosis because of organ system involvement including the cardiovascular (heart and blood vessels), nervous (peripheral nerves), and respiratory (lung and airways) systems. The 10-year survival rate for scleroderma is 60-80% because of life-threatening complications to these major organ systems.21
SSc is a complex and devastating disease requiring multiple treatment modalities. 22 There is no cure for scleroderma, and it represents a disease with significant unmet medical need.
BioMendics is focused on treating the dermatologic aspects of scleroderma. More specifically patients suffering with diffuse cutaneous SSc who have the greatest level of skin involvement. BioMendics is currently evaluating its Clearizome Technology to help remove excess collagen deposits to soften the skin and improve the lives of patients living with this disease.
*Systemic Sclerosis or Scleroderma are commonly used interchangeably. The most recent classification for systemic sclerosis was published in 2013 by the American College of Rheumatology and European League against Rheumatism collaborative initiative.