PANCREATITIS ASSOCIATED PROTEINS (PAP) FOR TREATMENT OF PANCREATITIS
Background: Pancreatitis is an inflammatory condition which resolves in the majority of patients. However, ~20% of patients experience severe morbidity of infection and necrosis which often require aggressive medical and surgical treatment. PAP proteins which are part of the regeneration (Reg) family of proteins have been shown to be upregulated in acute pancreatitis whereas many other proteins (digestive enzymes etc) are downregulated.
Pancreatitis market:
Ø Pancreatitis affects ~9/100,000 of the population.
Ø Incidence of ~35,000 patients per year in USA
Ø incidence increasing over the past 10-15 years
Ø Common problem of alcohol abuse, also in smokers
Ø Considerable costs for healthcare system and loss of work
Ø ~conservative costs of $60,000 per patient
Ø Therapies surgery, medicine and enzyme supplementation (57% market)
Preclinical data: We have previously shown that PAP appears to be important for pancreatitis resolution in that gene/protein knockdown of PAP (AS, RNAi, AB neutralization) correlates with worsening of pancreatitis severity (amylase, edema, inflammatory infiltrate, necrosis, etc). Recently, we (and others) have shown a direct immunmodulatory effect of PAP on the immune system which may be PAP isoform dependant
IP: PAP proteins for use in pancreatic diseases - Patent application filed.
References:
1. Lin YY, Viterbo D, Mueller CM, Stanek A, Smith-Norowitz TA, Drew H, Wadgaonkar R, Zenilman ME, Bluth MH. siRNA gene knockdown of pancreatitis-associated proteins (PAP) in rat acute pancreatitis. Pancreas 2008;36:402-410.
2. Viterbo D, Bluth MH, Lin YY, Mueller CM, Wadgaonkar R, Zenilman ME. Pancreatitis associated protein (PAP) 2 modulates inflammatory responses in macrophages. J Immunol 2008;181:1948-1958
3. Viterbo D, Bluth MH, Mueller CM, Zenilman ME. Mutational characterization of pancreatitis associated protein (PAP) 2 domains involved in mediating cytokine secretion in macrophages and the NF-κB pathway. J Immunol 2008;181:1959-1968.
4. Viterbo D, Callender GE, DiMaio T, Mueller CM, Smith-Norowitz TA, Zenilman ME, Bluth MH. Administration of anti-Reg and anti-PAPII antibodies worsens pancreatitis. Journal of the Pancreas 2009;10:15-23
Background: Pancreatitis is an inflammatory condition which resolves in the majority of patients. However, ~20% of patients experience severe morbidity of infection and necrosis which often require aggressive medical and surgical treatment. PAP proteins which are part of the regeneration (Reg) family of proteins have been shown to be upregulated in acute pancreatitis whereas many other proteins (digestive enzymes etc) are downregulated.
Pancreatitis market:
Ø Pancreatitis affects ~9/100,000 of the population.
Ø Incidence of ~35,000 patients per year in USA
Ø incidence increasing over the past 10-15 years
Ø Common problem of alcohol abuse, also in smokers
Ø Considerable costs for healthcare system and loss of work
Ø ~conservative costs of $60,000 per patient
Ø Therapies surgery, medicine and enzyme supplementation (57% market)
Preclinical data: We have previously shown that PAP appears to be important for pancreatitis resolution in that gene/protein knockdown of PAP (AS, RNAi, AB neutralization) correlates with worsening of pancreatitis severity (amylase, edema, inflammatory infiltrate, necrosis, etc). Recently, we (and others) have shown a direct immunmodulatory effect of PAP on the immune system which may be PAP isoform dependant
IP: PAP proteins for use in pancreatic diseases - Patent application filed.
References:
1. Lin YY, Viterbo D, Mueller CM, Stanek A, Smith-Norowitz TA, Drew H, Wadgaonkar R, Zenilman ME, Bluth MH. siRNA gene knockdown of pancreatitis-associated proteins (PAP) in rat acute pancreatitis. Pancreas 2008;36:402-410.
2. Viterbo D, Bluth MH, Lin YY, Mueller CM, Wadgaonkar R, Zenilman ME. Pancreatitis associated protein (PAP) 2 modulates inflammatory responses in macrophages. J Immunol 2008;181:1948-1958
3. Viterbo D, Bluth MH, Mueller CM, Zenilman ME. Mutational characterization of pancreatitis associated protein (PAP) 2 domains involved in mediating cytokine secretion in macrophages and the NF-κB pathway. J Immunol 2008;181:1959-1968.
4. Viterbo D, Callender GE, DiMaio T, Mueller CM, Smith-Norowitz TA, Zenilman ME, Bluth MH. Administration of anti-Reg and anti-PAPII antibodies worsens pancreatitis. Journal of the Pancreas 2009;10:15-23
