NIOXX, LLC is pursuing FDA testing and approval for a clinical treatment targeting the below diseases/injuries.  This technology has the potential to advance treatments for other disorders as research efforts progress.  However, our initial goals are focused primarily on the burn and wound treatment areas.

BURNS

Burns result from significant thermal injury to the body, and severe burns can have
significant impacts on both the physical and psychological health of patients. Burns are typically described as major, moderate, or minor, depending on their size and complexity.

Classification of Burns

The traditional classification of burns as first-, second-, and third-degree are based on a
visual assessment of the injury, but the true injury extends beyond what can be perceived
visually. For this reason, burns are better classified as partial- and full-thickness.

Partialthickness burns are defined by injury to the epidermis and the dermis. This classification can be further subcategorized into superficial partial-thickness burns, which only involve the epidermis, and deep partial-thickness burns, which involve the entire epidermis and part of the dermis. These burns tend to be painful because of the exposed nerve endings which result. Fullthickness burns, on the other hand, which involve the epidermis, dermis, as well as potentially the subcutaneous tissue, muscle, and bone, are typically painless, because the underlying nerve endings are destroyed. These burns often require skin grafting because of the severe extent of tissue damage present.

Burn Treatment

The treatment of burns is typically divided into three phases: emergent, acute, and
rehabilitative. During the emergent phase (48-72 hours post-burn) the primary treatment goals are to address the immediate medical problems resulting from the burn which are often unrelated to the actual skin injury. After the patient is stabilized, the burn wounds themselves are addressed. For first-degree/superficial partial-thickness burns, treatment is generally with topical moisturizers and no surgical intervention is required. For second degree/deep partial-thickness burns, some surgical debridement may be required before covering the burns with topical antimicrobial agents or synthetic wound dressings. For third degree/full thickness burns, extensive surgical debridement1 of the wound area is performed in order to decrease the risk of infection and to reduce the generation of inflammatory chemicals in the body which can lead to failure of internal organs. For these burns, either skin grafts from donor sites on the same patient, cadaver allografts or synthetic grafts are used to cover the wound sites. Depending on the location, size and depth of the burn, as well as the patient’s clinical course, a number of basic therapeutic strategies are employed, including:

• Open method: Usually used in treating burns of the face, neck and groin
• Semi-open method: Burns are cleaned, with dressings changed once a day. The
dressings are typically gauze covered with topical ointments
• Topical agents: The primary goal of such agents is to decrease infection and to speed
healing.
• Dressings: Usually a single layer of gauze coated with topical agents held in place by
a wrapping of coarse gauze
• Skin Grafts: Placed over burn wound cover the exposed surface area and speed
healing; also helps prevent development of contractures, preserve body heat and fluid
balance, and reduce incidence of infection.

Approximately 2.4 million people a year in the United States are treated for burn injuries.
650,000 of these cases require the care of a medical professional, and 75,000 require hospitalization. Of the hospitalized patients, 20,000 have burns covering at least 25% of their body surface. Each year, 8,000-12,000 patients die as a result of burn injuries, and
approximately one million patients sustain significant disabilities resulting from their burn injuries2. Burn injuries are second only to automobile accidents as the leading cause of accidental death in the U.S. Furthermore, they represent one of the most expensive catastrophic injuries to treat: a patient sustaining burns over 30% of their total body surface may require upwards of $200,000 in hospital costs and physician fees.

Medical Evidence of NO Involvement in Burn Healing

It is becoming increasingly clear that NO plays a significant role in wound healing. As early as 1998, NO was identified as having important roles in many stages of burn healing (Paulsen, Wurster et al. 1998). Studies indicate that increased NO synthesis in early stages of burns enhance healing (Shi and Wu 1998; Stallmeyer, Kampfer et al. 1999). A review of early work can be found in (Efron, Most et al. 2000). However, deleterious effects of excess NO generated by widespread burns have been implicated in cardiac malfunction (Soejima 2001). A very recent review (Rawlingson 2003) summarizes the medical situation to date. It appears that in extremely serious burns over a large portion of the human body, the nitric oxide generated is implicated in multiple organ failure. However, for small burns, where systemic effects are non-existent, the therapeutic value appears clear (Lindblom, Cassuto et al. 2000).

Efron, D. T., D. Most, et al. (2000). "Role of nitric oxide in wound healing." Curr Opin Clin Nutr Metab Care 3(3): 197-204.
Lindblom, L., J. Cassuto, et al. (2000). "Role of nitric oxide in the control of burn perfusion." Burns 26(1): 19-23.
Paulsen, S. M., S. H. Wurster, et al. (1998). "Expression of inducible nitric oxide synthase in human burn wounds." Wound Repair Regen 6(2): 142-8.
Rawlingson, A. (2003). "Nitric Oxide, inflammation and acute burn injury." Burns 29: 631-640.
Shi, S. and K. Wu (1998). "[Protective role of endogenous nitric oxide to microcirculation of rats during burn shock]." Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi 14(3): 214-7.
Soejima, K. F. C. S. L. D. T. C. S. A. S. D. L. T. (2001). "Role of nitric oxide in myocardial dysfunction after combined burn and smoke inhalation injury." Burns 27(8): 809-815.
Stallmeyer, B., H. Kampfer, et al. (1999). "The function of nitric oxide in wound repair: inhibition of inducible nitric oxide-synthase severely impairs wound reepithelialization." J Invest Dermatol 113(6): 1090-8.

 

DIABETIC FOOT WOUNDS

Diabetics are prone to foot ulcerations due to both neurologic and vascular complications. Neuropathic patients lose sensation in their feet/legs, which leads to an inability to discriminate between sharp vs. dull. Any cuts or trauma to the foot can go completely unnoticed for days or weeks in a patient with neuropathy. There is no known cure for neuropathy, but strict glucose control has been shown to slow the progression of the neuropathy. Microvascular disease is a significant problem for diabetics and can lead to ulcerations. Most of the problems caused by narrowing of the small arteries cannot be resolved surgically.
Diabetic Ulcer Treatment Market

The treatment market for diabetic ulcers is driven by the number of people with diabetes.
According to the National Institute for Diabetes and Digestive and Kidney Diseases NIDDK), an estimated 13 million people are known to have diabetes, with up to 5.2 million additional undiagnosed cases. An estimated 15% of patients with diabetes have foot ulcers yielding a diabetic ulcer patient population of 1.95 million, and 12-24% of these individuals eventually require amputation. In fact, Diabetes is the leading cause of lower extremity amputations in the U.S.: from 2000-2001, about 82,000 nontraumatic lower-limb amputations were performed on patients with diabetes. Once a diabetic patient develops a foot ulcer, they have a 66% chance of recurrence and a 12% risk of eventual amputation. The cost of treating single diabetic foot ulcer is estimated to be about $8000; in 1998, the annual healthcare expenditures related to diabetic foot ulcers were estimated to be more than $20 billion.

Medical Evidence for Nitric Oxide Therapy in Diabetic Wounds

In 1997, it was observed that there was reduced nitric oxide present in diabetic wounds (Huszka, Kaplar et al. 1997; Schaffer, Tantry et al. 1997). Since that time, various treatments that have some effect on healing these wounds have been associated with NO production – including hyperbaric treatments (Boykin 2000). An excellent review can be found in (Childress and Stechmiller 2002). This past year two studies have appeared where enhanced nitric oxide synthesis is used as a treatment method for this disease (Shi, Most et al. 2003; Weller 2003). Topical NO seems a logical additional treatment target for this major health problem.

References

Boykin, J. V. J., MD (2000). "The Nitric Oxide Connection: Hyperbaric Oxygen Therapy, Becaplermin, and Diabetic Ulcer Management." The Journal for Prevention adn Healing 13: 169-174.
Childress, B. B. and J. K. Stechmiller (2002). "Role of nitric oxide in wound healing." Biol Res Nurs 4(1): 5-15.
Huszka, M., M. Kaplar, et al. (1997). "The association of reduced endothelium derived relaxing factor-NO production with endothelial damage and increased in vivo platelet activation in patients with diabetes mellitus." Thromb Res 86(2): 173-80.
Schaffer, M. R., U. Tantry, et al. (1997). "Diabetes-impaired healing and reduced wound nitric oxide synthesis: a possible pathophysiologic correlation." Surgery 121(5): 513-9.
Shi, H. P., D. Most, et al. (2003). "Supplemental L-arginine enhances wound healing in diabetic rats." Wound Repair Regen 11(3): 198-203.
Weller, R. (2003). "Nitric oxide donors and the skin: useful therapeutic agents?" Clin Sci (Lond) 105(5): 533-5.

 

ECZEMA

Eczema, or dermatitis as it is sometimes called, is a group of skin conditions characterized by symptoms such as hot, dry, and itchy skin. In severe cases, skin may become broken, raw, and bleeding. Eczema is not contagious, but with treatment, inflammation can be reduced. However, those with eczema will always be sensitive to flare-ups and need extra care. The pathogenesis of eczema is not known, but very recent work by Guzik, et. al.(Guzik, Adamek-Guzik et al. 2002) indicates that nitric oxide is being over produced in the disease. Similar conclusions have been reached for psoriasis(Omerod 1998). But unintuitively, it has been found (Antipolis 2001) that topical addition of NO may be of therapeutic value.

Antipolis, S. (2001). NicOx's Nitric Oxide-Releasing Steroid, NCX 1022, Shows Promising Clinical Results in Skin Blanching. PR Newswire.
Guzik, T. J., T. Adamek-Guzik, et al. (2002). "Nitric oxide metabolite levels in children and adult patients with atopic eczema/dermatitis syndrome." Allergy 57(9): 856.
Omerod, A. W. R. C. P. B. N. R., SH; Grabowski, P; Herriot, R. (1998). "Detection of nitric oxide and nitric oxide synthases in psoriasis." Archives of Dermatological Research 290: 3-8.