Treatment and Management
Plasminogen Deficiency (PLGD) is a rare condition for which there is no formal standard of care or established protocol. Historically, this has been due to the lack of supply and commercial availability of a purified plasminogen (PLG) protein needed for the small number of patients with this condition.1, 2, 3, 4
Currently, there is no effective therapy commercially available for this condition. A variety of treatments have been tried in recent years with PLG replacement being the most promising.1, 2, 3, 4 Prometic Life Sciences is developing novel, purified protein replacement therapy for PLGD.
Past Attempts Have Had Limited Success
Although the characteristic lesions are now better recognized and PLG levels are accurately and easily measured, treatment remains inadequate.5
When lesions form in the eye (ligneous conjunctivitis), congenital PLGD has been managed case by case with varying levels of success.1, 2, 3, 4, 5, 6
Surgical Removal of the Fibrinous Growths
Surgery has been the primary approach to treating ligneous conjunctivitis, but relief is temporary, and the lesions usually return.3
High Doses of Intravenous Corticosteroids
Steroidal treatment given intravenously has also had limited success in treating the lesions.3
Topical Treatment on the Lesions
Therapy applied directly on the lesions did not completely or consistently treat them or prevent them from reforming.7, 8, 9, 10
Many topical treatments have been tried over the years. Among those explored were hyaluronidase (an enzyme), heparin (a blood thinner or anticoagulant) used in combination with corticosteroids or alpha-chymotrypsin, and immunosuppressants (drugs that suppress the immune system), such as cyclosporine and azathioprine.7, 8, 9, 10
The Success of PLG Concentrates
Progress Reported in Studies Using Replacement Therapy
PLG concentrates given locally (specific to one area) and systemically (circulating throughout the body) have been shown to effectively prevent lesions from reforming.1, 2, 3, 4
- Locally administered fresh frozen plasma (which contains PLG) and other PLG-containing eye drops have shown some effectiveness in treating eye lesions associated with ligneous conjunctivitis.¹ Continued topical administration of PLG-containing eye drops can treat the lesion and prevent regrowth.
- Systemic administration of PLG concentrates has also been shown to partially resolve the lesions.6,11
PLG Replacement Therapy Offers New Hope
Lysine and glutamic acid are alpha-amino acids involved in the making of proteins in the body. These make up the two main purified forms of concentrate in two notable PLG replacement studies.6, 12
Lysine-conjugated Plasminogen (Lys-PLG)
Lys-PLG, one of the two main forms of replacement PLG, was continuously infused and then injected daily in a 6-month-old infant with ligneous conjunctivitis. The lesions completely resolved within 4 weeks, and respiratory tract and wound healing functions returned to normal.6 Lys-PLG is no longer available for commercial sale.
Glutamic-conjugated PLG (Glu-PLG)
Glu-PLG, the other main form of replacement PLG, was given to a child on a ventilator with lesions in the lungs. Remarkable reductions were observed after only 6 weeks.12
Clinical Trials Are Underway and Ongoing
While there is no replacement product approved for the treatment of PLGD, a clinical trial with Glu-PLG are in process.5, 12
Prometic Life Sciences is developing a medicine that contains purified PLG (Glue-PLG) extracted from human blood and is currently conducting a clinical trial in the United States and Europe.¹³ When given by injection to patients who lack working PLG of their own, it is expected to replace the missing protein in their blood and correct the symptoms of the condition.14
This new, plasma-derived protein replacement therapy is currently in a clinical trial (Phase2/3) to demonstrate safety and tolerability and explore clinical effectiveness in patients with congenital PLGD.
Plasminogen IV is under evaluation by the FDA, with anticipated approval in 2018. An accelerated review only happens in serious conditions where there is a meaningful advantage over other available therapies.13
Study centers in Europe have initiated patients on therapy with investigation ongoing in 2017. This novel therapeutic formulation of PLG is intended for the treatment of congenital PLGD.14
More information about these clinical trials is available at ClinicalTrials.gov.
1. Heidemann DG, Williams GA, Hartzer M, Ohanian A, Citron ME. Treatment of ligneous conjunctivitis with topical plasmin and topical plasminogen. Cornea. 2003;22:760–762.
2. Watts P, Suresh P, Mezer E, et al. Effective treatment of ligneous conjunctivitis with topical plasminogen. Am J Ophthalmol. 2002;133:451–455.
3. Pergantou H, Likaki D, Fotopoulou M, Katsarou O, Xafaki P, Platokouki H. Management of ligneous conjunctivitis in a child with plasminogen deficiency. Eur J Pediatr. 2011;170:1333-1336.
4. Tabarra KF. Prevention of ligneous conjunctivitis by topical and subconjunctival fresh frozen plasma. Am J Ophthalmol. 2004;138(2):299-300.
5. Mehta R, Shapiro AD. Plasminogen activator inhibitor type I deficiency. Haemophilia. 2008;14:1255-1260.
6. Schott D, Dempfle C-E, Beck P, et al. Therapy with a purified plasminogen concentrate in an infant with ligneous conjunctivitis and homozygous plasminogen deficiency. N Engl J Med. 1998;339(23):1679-1686.
7. Schuster V, Hugle B, Tefs K. Plasminogen deficiency. J Thromb Haemost. 2007;5(12):2315-2322.
8. De Cock R, Ficker LA, Dart JG, Garner A, Wright P. Topical heparin in the treatment of ligneous conjunctivitis. Ophthalmology. 1995;102(11):1654-1659.
9. Silva GB, Bariani C, Mendonca EF, Batista AC. Clinical manifestations due to severe plasminogen deficiency: a case report. J Dent Child. 2006;73(3):179-182.
10. Rubin EM, Krauss RM, Spangler EA, Verstuyft JG, Clift SM. Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI. Nature. 1991;353(6341):265-267.
11. Kraft J, Lieb W, Zeitler P, Schuster V. Ligneous conjunctivitis in a girl with severe type I plasminogen deficiency PMID abstract 11045349]. Graefes Arch Clin Exp Ophthalmol. 2000;238:797–800.
12. Schneppenheim R, Moran J, Hassenpflug W, Schrum J, Schneppenheim S, Müller-Stöver S. Pending publication in peer-reviewed journal.
13. Data on file. Prometic Life Sciences Inc.
14. European Medicines Agency (EMA). EU/3/15/1511 Orphan designation granted by the European Commission to Prometic BioTherapeutics Ltd, United Kingdom, for human plasminogen for the treatment of plasminogen deficiency. Published
August, 18, 2015. Published here. Accessed May 13, 2016.
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