PMID- 30564619
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240405
IS  - 2328-9503 (Print)
IS  - 2328-9503 (Electronic)
IS  - 2328-9503 (Linking)
VI  - 5
IP  - 12
DP  - 2018 Dec
TI  - Pilot trial of inosine to elevate urate levels in amyotrophic lateral sclerosis.
PG  - 1522-1533
LID - 10.1002/acn3.671 [doi]
AB  - OBJECTIVE: To test the safety, tolerability, and urate-elevating capability of 
      the urate precursor inosine taken orally or by feeding tube in people with 
      amyotrophic lateral sclerosis (ALS). METHODS: This was a pilot, open-label trial 
      in 25 participants with ALS. Treatment duration was 12 weeks. The dose of inosine 
      was titrated at pre-specified time points to elevate serum urate levels to 7-8 
      mg/dL. Primary outcomes were safety (as assessed by the occurrence of adverse 
      events [AEs]) and tolerability (defined as the ability to complete the 12-week 
      study on study drug). Secondary outcomes included biomarkers of oxidative stress 
      and damage. As an exploratory analysis, observed outcomes were compared with a 
      virtual control arm built using prediction algorithms to estimate ALSFRS-R 
      scores. RESULTS: Twenty-four out of 25 participants (96%) completed 12 weeks of 
      study drug treatment. One participant was unable to comply with study visits and 
      was lost to follow-up. Serum urate rose to target levels in 6 weeks. No serious 
      AEs attributed to study drug and no AEs of special concern, such as urolithiasis 
      and gout, occurred. Selected biomarkers of oxidative stress and damage had 
      significant changes during the study period. Observed changes in ALSFRS-R did not 
      differ from baseline predictions. INTERPRETATION: Inosine appeared safe, well 
      tolerated, and effective in raising serum urate levels in people with ALS. These 
      findings, together with epidemiological observations and preclinical data 
      supporting a neuroprotective role of urate in ALS models, provide the rationale 
      for larger clinical trials testing inosine as a potential disease-modifying 
      therapy for ALS.
FAU - Nicholson, Katharine
AU  - Nicholson K
AD  - Neurological Clinical Research Institute (NCRI) Massachusetts General Hospital 
      (MGH) Boston Massachusetts.
FAU - Chan, James
AU  - Chan J
AD  - MGH Biostatistics Center Boston Massachusetts.
FAU - Macklin, Eric A
AU  - Macklin EA
AD  - MGH Biostatistics Center Boston Massachusetts.
FAU - Levine-Weinberg, Mark
AU  - Levine-Weinberg M
AD  - Neurological Clinical Research Institute (NCRI) Massachusetts General Hospital 
      (MGH) Boston Massachusetts.
FAU - Breen, Christopher
AU  - Breen C
AD  - Neurological Clinical Research Institute (NCRI) Massachusetts General Hospital 
      (MGH) Boston Massachusetts.
FAU - Bakshi, Rachit
AU  - Bakshi R
AD  - MassGeneral Institute for Neurodegenerative Disease Boston Massachusetts.
FAU - Grasso, Daniela L
AU  - Grasso DL
AD  - Neurological Clinical Research Institute (NCRI) Massachusetts General Hospital 
      (MGH) Boston Massachusetts.
FAU - Wills, Anne-Marie
AU  - Wills AM
AD  - Neurological Clinical Research Institute (NCRI) Massachusetts General Hospital 
      (MGH) Boston Massachusetts.
FAU - Jahandideh, Samad
AU  - Jahandideh S
AD  - Origent Data Sciences Boston Massachusetts.
FAU - Taylor, Albert A
AU  - Taylor AA
AD  - Origent Data Sciences Boston Massachusetts.
FAU - Beaulieu, Danielle
AU  - Beaulieu D
AD  - Origent Data Sciences Boston Massachusetts.
FAU - Ennist, David L
AU  - Ennist DL
AD  - Origent Data Sciences Boston Massachusetts.
FAU - Andronesi, Ovidiu
AU  - Andronesi O
AD  - MGH Department of Radiology A. A. Martinos Center for Biomedical Imaging Boston 
      Massachusetts.
FAU - Ratai, Eva-Maria
AU  - Ratai EM
AD  - MGH Department of Radiology A. A. Martinos Center for Biomedical Imaging Boston 
      Massachusetts.
FAU - Schwarzschild, Michael A
AU  - Schwarzschild MA
AD  - MassGeneral Institute for Neurodegenerative Disease Boston Massachusetts.
FAU - Cudkowicz, Merit
AU  - Cudkowicz M
AD  - Neurological Clinical Research Institute (NCRI) Massachusetts General Hospital 
      (MGH) Boston Massachusetts.
FAU - Paganoni, Sabrina
AU  - Paganoni S
AD  - Neurological Clinical Research Institute (NCRI) Massachusetts General Hospital 
      (MGH) Boston Massachusetts.
AD  - Spaulding Rehabilitation Hospital Boston Massachusetts.
LA  - eng
PT  - Journal Article
DEP - 20181022
PL  - United States
TA  - Ann Clin Transl Neurol
JT  - Annals of clinical and translational neurology
JID - 101623278
PMC - PMC6292193
EDAT- 2018/12/20 06:00
MHDA- 2018/12/20 06:01
PMCR- 2018/10/22
CRDT- 2018/12/20 06:00
PHST- 2018/05/14 00:00 [received]
PHST- 2018/08/13 00:00 [revised]
PHST- 2018/09/10 00:00 [accepted]
PHST- 2018/12/20 06:00 [entrez]
PHST- 2018/12/20 06:00 [pubmed]
PHST- 2018/12/20 06:01 [medline]
PHST- 2018/10/22 00:00 [pmc-release]
AID - ACN3671 [pii]
AID - 10.1002/acn3.671 [doi]
PST - epublish
SO  - Ann Clin Transl Neurol. 2018 Oct 22;5(12):1522-1533. doi: 10.1002/acn3.671. 
      eCollection 2018 Dec.