Contributions
Abstract: P1786
Type: Poster Sessions
Abstract Category: N/A
JDS-MB-001 is a novel form of D-biotin with significantly enhanced solubility, absorption and activity. High dose pharmaceutical grade biotin (300 mg/day) is being researched as a potential treatment for multiple sclerosis, as it is thought to promote remyelination and normal immune cell function by restoring the activity of biotin-dependent carboxylases (BDCs) involved in fatty acid synthesis and energy production. This study was carried out to evaluate and compare the absorption and activity of JDS-MB-001 to pharmaceutical grade D-biotin in a lysolecithin (LPC)-induced hippocampal demyelination animal model.
Male Wistar rats were randomized to receive: 1.5 µl of sterile saline (Control); 1.5 µl of LPC 1% (LPC); LPC and 0.9 mg/day (30 mg human equivalent dose (HED)) of D-biotin (B1); LPC and 9 mg/day (300 mg HED) of D-biotin (B2); LPC and 0.9 mg/day (30 mg HED) of JDS-MB-001 (MB1); or LPC and 9 mg/day (300 mg HED) of JDS-MB-001 (MB2). LPC and sterile saline were injected into hippocampal CA1 region. Biotin was given via oral gavage for four weeks, and then rats were sacrificed to collect blood and brain tissue samples.
The LPC group had higher levels of brain inflammatory factors and lower levels of BDCs and biotin compared to control (p< 0.05). Brain biotin levels were higher in the JDS-MB-001 groups compared to corresponding doses of D-biotin (p< 0.05). Serum and brain biotin levels were greatest in the MB2 group versus all groups (p< 0.05). Brain levels of inflammatory factors tumor necrosis factor alpha, CXC chemokine ligand 16 and interleukin 6 were lowest in the MB2 group versus all treatment groups (p< 0.05), while levels did not differ between the B2 and MB1 groups. Brain acetyl-CoA carboxylase 2 levels were highest in the MB2 group versus all treatment groups (p< 0.05), with levels no different than control. Brain methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase levels were brought back to control levels in only the MB1 and MB2 groups.
In conclusion, JDS-MB-001 was shown to be significantly more bioavailable and efficacious in reducing inflammatory markers and increasing BDCs than pharmaceutical grade D-biotin. For various endpoints, the 300 mg HED of JDS-MB-001 had the greatest activity, and the 30 mg HED of JDS-MB-001 had activity greater than or equal to the 300 mg HED of D-biotin. The results of this study support the potential benefits of JDS-MB-001 in the treatment of demyelinating diseases.
Disclosure: This study was conducted at Firat University, Elazig, Turkey, and funded by JDS Therapeutics, LLC. JK is an employee and researcher at JDS Therapeutics, LLC. SPO is an employee and researcher at JDS Therapeutics, LLC. SS is an employee and researcher at JDS Therapeutics, LLC. KS has received research and travel grants from JDS Therapeutics, LLC. CO is a researcher in KS's laboratory and reports no additional disclosures. MT is a researcher in KS's laboratory and reports no additional disclosures. IHO is a researcher in KS´s laboratory and reports no additional disclosures. SC is a researcher in KS's laboratory and reports no additional disclosures.
Abstract: P1786
Type: Poster Sessions
Abstract Category: N/A
JDS-MB-001 is a novel form of D-biotin with significantly enhanced solubility, absorption and activity. High dose pharmaceutical grade biotin (300 mg/day) is being researched as a potential treatment for multiple sclerosis, as it is thought to promote remyelination and normal immune cell function by restoring the activity of biotin-dependent carboxylases (BDCs) involved in fatty acid synthesis and energy production. This study was carried out to evaluate and compare the absorption and activity of JDS-MB-001 to pharmaceutical grade D-biotin in a lysolecithin (LPC)-induced hippocampal demyelination animal model.
Male Wistar rats were randomized to receive: 1.5 µl of sterile saline (Control); 1.5 µl of LPC 1% (LPC); LPC and 0.9 mg/day (30 mg human equivalent dose (HED)) of D-biotin (B1); LPC and 9 mg/day (300 mg HED) of D-biotin (B2); LPC and 0.9 mg/day (30 mg HED) of JDS-MB-001 (MB1); or LPC and 9 mg/day (300 mg HED) of JDS-MB-001 (MB2). LPC and sterile saline were injected into hippocampal CA1 region. Biotin was given via oral gavage for four weeks, and then rats were sacrificed to collect blood and brain tissue samples.
The LPC group had higher levels of brain inflammatory factors and lower levels of BDCs and biotin compared to control (p< 0.05). Brain biotin levels were higher in the JDS-MB-001 groups compared to corresponding doses of D-biotin (p< 0.05). Serum and brain biotin levels were greatest in the MB2 group versus all groups (p< 0.05). Brain levels of inflammatory factors tumor necrosis factor alpha, CXC chemokine ligand 16 and interleukin 6 were lowest in the MB2 group versus all treatment groups (p< 0.05), while levels did not differ between the B2 and MB1 groups. Brain acetyl-CoA carboxylase 2 levels were highest in the MB2 group versus all treatment groups (p< 0.05), with levels no different than control. Brain methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase levels were brought back to control levels in only the MB1 and MB2 groups.
In conclusion, JDS-MB-001 was shown to be significantly more bioavailable and efficacious in reducing inflammatory markers and increasing BDCs than pharmaceutical grade D-biotin. For various endpoints, the 300 mg HED of JDS-MB-001 had the greatest activity, and the 30 mg HED of JDS-MB-001 had activity greater than or equal to the 300 mg HED of D-biotin. The results of this study support the potential benefits of JDS-MB-001 in the treatment of demyelinating diseases.
Disclosure: This study was conducted at Firat University, Elazig, Turkey, and funded by JDS Therapeutics, LLC. JK is an employee and researcher at JDS Therapeutics, LLC. SPO is an employee and researcher at JDS Therapeutics, LLC. SS is an employee and researcher at JDS Therapeutics, LLC. KS has received research and travel grants from JDS Therapeutics, LLC. CO is a researcher in KS's laboratory and reports no additional disclosures. MT is a researcher in KS's laboratory and reports no additional disclosures. IHO is a researcher in KS´s laboratory and reports no additional disclosures. SC is a researcher in KS's laboratory and reports no additional disclosures.