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Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited disorder characterized by skin fragility, blistering, and multiple skin wounds with no currently approved or consistently effective treatment. It is due to mutations in the gene encoding type VII collagen (C7). Using recombinant human C7 (rhC7) purified from human dermal fibroblasts (FB-rhC7), we showed previously that intravenously injected rhC7 distributed to engrafted RDEB skin, incorporated into its dermal–epidermal junction (DEJ), and reversed the RDEB disease phenotype. Human dermal fibroblasts, however, are not used for commercial production of therapeutic proteins. Therefore, we generated rhC7 from Chinese hamster ovary (CHO) cells. The CHO–derived recombinant type VII collagen (CHO-rhC7), similar to FB-rhC7, was secreted as a correctly folded, disulfide-bonded, helical trimer resistant to protease degradation. CHO-rhC7 bound to fibronectin and promoted human keratinocyte migration in vitro. A single dose of CHO-rhC7, administered intravenously into new-born C7-null RDEB mice, incorporated into the DEJ of multiple skin sites, tongue and esophagus, restored anchoring fibrils, improved dermal–epidermal adherence, and increased the animals’ life span. Furthermore, no circulating or tissue-bound anti-C7 antibodies were observed in the mice. These data demonstrate the efficacy of CHO-rhC7 in a preclinical murine model of RDEB.

Background: Metformin is commonly used in the treatment of diabetes mellitus due to its low cost, ease of administration and titration, and favorable side effect profile as it does not cause weight gain and rarely causes overt hypoglycemia. An important yet rare side effect of metformin use is metformin associated lactic acidosis (MALA) which can be seen in patients with significant renal impairment and is associated with high mortality. Clinical Case: We present a 54-year-old man with hypertension, type 2 diabetes mellitus, and recently diagnosed end-stage renal disease (ESRD) on hemodialysis who presented with shortness of breath and syncope and found to have an elevated lactate to 40.5 mmol/L (reference range: 0.5-2 mmol/L). Notably, the patient was admitted at an outside hospital two and a half weeks prior for a new diagnosis of ESRD and initiated on hemodialysis three times a week. At the time of discharge from his prior hospitalization, he was instructed to continue his diabetes medications: metformin 1g twice a day, glipizide 10 mg twice a day, and pioglitazone 30 mg daily. The patient was admitted to the intensive care unit and found to have MALA. Nephrology was consulted and the patient clinically improved with hemodialysis. Within six hours of presentation, the patient’s clinical course rapidly improved with complete resolution of lactic acidosis and hemodynamic instability within 48 hours. Conclusion: Although metformin is the most commonly used drug in diabetes mellitus, the side effect of metformin associated lactic acidosis is rarely seen in the inpatient setting. Patients with ESRD are at high risk for complications resulting from poor medication management. However, because metformin is primarily renally cleared, it should be discontinued in those with significant renal impairment. With increased awareness and understanding of MALA, providers can prevent MALA by appropriately stopping or dose reducing metformin in patients with chronic kidney disease. Educating patients on their medications—including their uses, side effects, and drug-drug and drug-food interactions—could help reduce the aforementioned medication-related problems. Clinicians should have a high suspicion of metformin associated lactic acidosis in any patient presenting with multi-organ failure due to its variable clinical presentation. If MALA is suspected, providers should consult nephrology so that patients can be started on hemodialysis.