Efficacy of prosultiamine treatment in patients with human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis: results from an open-label clinical trial.
BACKGROUND
Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic myelopathy characterized by motor dysfunction of the lower extremities and urinary disturbance. Immunomodulatory treatments are the main strategy for HAM/TSP, but several issues are associated with long-term treatment. We conducted a clinical trial with prosultiamine (which has apoptotic activity against HTLV-I-infected cells) as a novel therapy in HAM/TSP patients.


METHODS
We enrolled 24 HAM/TSP patients in this open-label clinical trial. Prosultiamine (300 mg, orally) was administered once daily for 12 weeks. We monitored changes in the motor function of the lower extremities and urinary function as well as copy numbers of the HTLV-I provirus in peripheral blood mononuclear cells (PBMCs).


RESULTS
Improvement in the motor function of the lower extremities based on a reduction in spasticity (for example, decrease in time required for walking and descending a flight of stairs) was observed. In an urodynamic study (UDS), bladder capacity and detrusor pressure and then maximum flow rate increased significantly. Detrusor overactivity and detrusor-sphincter dyssynergia improved in 68.8% and 45.5% of patients observed at pretreatment, respectively. Improvement in UDS corresponded with improvements in the score of nocturia-quality of life questionnaire. HTLV-I proviral copy numbers in PBMCs decreased significantly (approximately 15.4%) compared with pretreatment levels.


CONCLUSIONS
These data suggest that prosultiamine can safely improve motor dysfunction of the lower extremities and urinary disturbance as well as reduce HTLV-I provirus levels in peripheral blood. It therefore has potential as a new therapeutic tool for HAM/TSP patients.


BACKGROUND
University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) number, UMIN000005969. Please see related commentary: http://www.biomedcentral.com/1741-7015/11/183.
Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. tatsu@nagasaki-u.ac.jp.
Tatsufumi
T
Nakamura
Tomohiro
T
Matsuo
Taku
T
Fukuda
Shinji
S
Yamato
Kentaro
K
Yamaguchi
Ikuo
I
Kinoshita
Toshio
T
Matsuzaki
Yoshihiro
Y
Nishiura
Kunihiko
K
Nagasato
Tomoko
T
Narita-Masuda
Hideki
H
Nakamura
Katsuya
K
Satoh
Hitoshi
H
Sasaki
Hideki
H
Sakai
Atsushi
A
Kawakami
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D015490:HTLV-I Infections / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007866:Leg / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D011533:Proviruses / Q000302:isolation & purification; D013831:Thiamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D014554:Urination / Q000502:physiology; D019562:Viral Load; D055815:Young Adult
C013294:prosultiamine; D013831:Thiamine