PMID- 32092460
OWN - NLM
STAT- MEDLINE
DCOM- 20210104
LR  - 20210104
IS  - 1525-5069 (Electronic)
IS  - 1525-5050 (Linking)
VI  - 105
DP  - 2020 Apr
TI  - ACTON PROLONGATUM(R) suppresses spasms head to head with Acthar(R) Gel in the model 
      of infantile spasms.
PG  - 106950
LID - S1525-5050(19)31388-5 [pii]
LID - 10.1016/j.yebeh.2020.106950 [doi]
AB  - Epileptic spasms during infancy (infantile spasms, IS) are a rare epilepsy 
      syndrome with dire prognosis. Current treatments, effective in about 55% of 
      cases, include hormonal therapy (adrenocorticotropic hormone [ACTH] = 
      adrenocorticotropin or corticosteroids) or vigabatrin (also in combination with 
      hormones). In addition to their limited efficacy, these treatments may also carry 
      serious adverse effects. Thus, the search for new effective drugs to treat this 
      rare disease is desirable. In this study, we determined the efficacy of ACTON 
      PROLONGATUM(R) (AP; Ferring Pharmaceuticals) in comparison with Acthar(R) Gel 
      (Mallinckrodt) and full 39 amino-acid rat ACTH molecule (Genscript) in the rodent 
      model of IS consisting of prenatal priming with betamethasone and repeated 
      postnatal trigger of spasms with N-methyl-d-aspartate. Treatment with these ACTH 
      varieties was given on postnatal days (P)12, P13, and P14 in a prospective test 
      (treatment onset on P12 AFTER induction of spasms). Two independent arms were 
      investigated: subcutaneous (SC) and intramuscular (IM) deliveries that were 
      evaluated separately. In the SC arm, there was a significant suppression of the 
      number of spasms after both Acthar(R) Gel and AP on P13 and P15 compared with 
      gelatin control. In the IM arm, a significant suppression of the number of spasms 
      was achieved only after AP on both P13 and P15 indicating that after IM delivery, 
      Acthar(R) Gel was not as effective as AP. In this study, we confirmed the efficacy 
      of two ACTH formulations (gelatin-based Acthar(R) Gel and carboxymethyl 
      cellulose-based AP) in the model of IS. ACTON PROLONGATUM(R) may become a valuable 
      therapy for IS. In our animal model, AP was at least as efficient as the standard 
      of care, Acthar(R) Gel.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Chern, Chian-Ru
AU  - Chern CR
AD  - Department of Cell Biology & Anatomy, New York Medical College, School of 
      Medicine, Valhalla, NY 10595, USA.
FAU - Chern, Chian-Jiang
AU  - Chern CJ
AD  - Department of Cell Biology & Anatomy, New York Medical College, School of 
      Medicine, Valhalla, NY 10595, USA.
FAU - Veliskova, Jana
AU  - Veliskova J
AD  - Department of Cell Biology & Anatomy, New York Medical College, School of 
      Medicine, Valhalla, NY 10595, USA; Department of Obstetrics & Gynecology, New 
      York Medical College, School of Medicine, Valhalla, NY 10595, USA; Department of 
      Neurology, New York Medical College, School of Medicine, Valhalla, NY 10595, USA.
FAU - Velisek, Libor
AU  - Velisek L
AD  - Department of Cell Biology & Anatomy, New York Medical College, School of 
      Medicine, Valhalla, NY 10595, USA; Department of Neurology, New York Medical 
      College, School of Medicine, Valhalla, NY 10595, USA; Department of Pediatrics, 
      New York Medical College, School of Medicine, Valhalla, NY 10595, USA. Electronic 
      address: Libor_Velisek@nymc.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200221
PL  - United States
TA  - Epilepsy Behav
JT  - Epilepsy & behavior : E&B
JID - 100892858
RN  - 0 (Anticonvulsants)
RN  - 0 (Gels)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - GR120KRT6K (Vigabatrin)
SB  - IM
MH  - Adrenocorticotropic Hormone/genetics/*therapeutic use
MH  - Amino Acid Sequence
MH  - Animals
MH  - Animals, Newborn
MH  - Anticonvulsants/*therapeutic use
MH  - *Disease Models, Animal
MH  - Female
MH  - Gels
MH  - Humans
MH  - Infant, Newborn
MH  - Pregnancy
MH  - Prospective Studies
MH  - Rats
MH  - Spasms, Infantile/*drug therapy/physiopathology
MH  - Vigabatrin/therapeutic use
OTO - NOTNLM
OT  - ACTH
OT  - ACTON PROLONGATUM(R)
OT  - Acthar(R) Gel
OT  - Infantile spasms
OT  - Rodent model
COIS- Declaration of competing interest None, except for the funding sources.
EDAT- 2020/02/25 06:00
MHDA- 2021/01/05 06:00
CRDT- 2020/02/25 06:00
PHST- 2019/12/19 00:00 [received]
PHST- 2020/01/17 00:00 [revised]
PHST- 2020/01/26 00:00 [accepted]
PHST- 2020/02/25 06:00 [pubmed]
PHST- 2021/01/05 06:00 [medline]
PHST- 2020/02/25 06:00 [entrez]
AID - S1525-5050(19)31388-5 [pii]
AID - 10.1016/j.yebeh.2020.106950 [doi]
PST - ppublish
SO  - Epilepsy Behav. 2020 Apr;105:106950. doi: 10.1016/j.yebeh.2020.106950. Epub 2020 
      Feb 21.