PMID- 19327618
OWN - NLM
STAT- MEDLINE
DCOM- 20090722
LR  - 20211020
IS  - 1532-8414 (Electronic)
IS  - 1071-9164 (Print)
IS  - 1071-9164 (Linking)
VI  - 15
IP  - 3
DP  - 2009 Apr
TI  - Calcium upregulation by percutaneous administration of gene therapy in cardiac 
      disease (CUPID Trial), a first-in-human phase 1/2 clinical trial.
PG  - 171-81
LID - 10.1016/j.cardfail.2009.01.013 [doi]
AB  - BACKGROUND: SERCA2a deficiency is commonly seen in advanced heart failure (HF). 
      This study is designed to investigate safety and biological effects of enzyme 
      replacement using gene transfer in patients with advanced HF. METHODS AND 
      RESULTS: A total of 9 patients with advanced HF (New York Heart Association 
      [NYHA] Class III/IV, ejection fraction [EF] < or = 30%, maximal oxygen uptake 
      [VO2 max] <16 mL.kg.min, with maximal pharmacological and device therapy) 
      received a single intracoronary infusion of AAV1/SERCA2a in the open-label 
      portion of this ongoing study. Doses administered ranged from 1.4 x 10(11) to 3 x 
      10(12) DNase resistant particles per patient. We present 6- to 12-month follow-up 
      data for these patients. AAV1/SERCA2a demonstrated an acceptable safety profile 
      in this advanced HF population. Of the 9 patients treated, several demonstrated 
      improvements from baseline to month 6 across a number of parameters important in 
      HF, including symptomatic (NYHA and Minnesota Living with Heart Failure 
      Questionnaire, 5 patients), functional (6-minute walk test and VO2 max, 4 
      patients), biomarker (NT-ProBNP, 2 patients), and LV function/remodeling (EF and 
      end-systolic volume, 5 patients). Of note, 2 patients who failed to improve had 
      preexisting anti-AAV1 neutralizing antibodies. CONCLUSIONS: Quantitative evidence 
      of biological activity across a number of parameters important for assessing HF 
      status could be detected in several patients without preexisting neutralizing 
      antibodies in this open-label study, although the number of patients in each 
      cohort is too small to conduct statistical analyses. These findings support the 
      initiation of the Phase 2 double-blind, placebo-controlled portion of this study.
FAU - Jaski, Brian E
AU  - Jaski BE
AD  - San Diego Cardiac Center, San Diego, California 92123, USA. bjaski@sdcardiac.com
FAU - Jessup, Mariell L
AU  - Jessup ML
FAU - Mancini, Donna M
AU  - Mancini DM
FAU - Cappola, Thomas P
AU  - Cappola TP
FAU - Pauly, Daniel F
AU  - Pauly DF
FAU - Greenberg, Barry
AU  - Greenberg B
FAU - Borow, Kenneth
AU  - Borow K
FAU - Dittrich, Howard
AU  - Dittrich H
FAU - Zsebo, Krisztina M
AU  - Zsebo KM
FAU - Hajjar, Roger J
AU  - Hajjar RJ
CN  - Calcium Up-Regulation by Percutaneous Administration of Gene Therapy In Cardiac 
      Disease (CUPID) Trial Investigators
LA  - eng
GR  - R01 HL078731/HL/NHLBI NIH HHS/United States
GR  - R01 HL088434/HL/NHLBI NIH HHS/United States
GR  - R01 HL080498/HL/NHLBI NIH HHS/United States
GR  - HL080498/HL/NHLBI NIH HHS/United States
GR  - R01 HL083156-03/HL/NHLBI NIH HHS/United States
GR  - HL083156/HL/NHLBI NIH HHS/United States
GR  - R01 HL083156/HL/NHLBI NIH HHS/United States
GR  - HL 78731/HL/NHLBI NIH HHS/United States
GR  - R01 HL078691/HL/NHLBI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Card Fail
JT  - Journal of cardiac failure
JID - 9442138
RN  - 0 (Peptide Fragments)
RN  - 0 (pro-brain natriuretic peptide (1-76))
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
SB  - IM
MH  - Exercise Test
MH  - Female
MH  - *Genetic Therapy
MH  - Heart Failure/genetics/*therapy
MH  - Humans
MH  - Infusions, Intra-Arterial
MH  - Male
MH  - Middle Aged
MH  - Natriuretic Peptide, Brain/blood
MH  - Oxygen Consumption
MH  - Peptide Fragments/blood
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/administration & 
      dosage/*genetics
MH  - Stroke Volume
MH  - Systole
MH  - Up-Regulation
MH  - Ventricular Remodeling
PMC - PMC2752875
MID - NIHMS127565
EDAT- 2009/03/31 09:00
MHDA- 2009/07/23 09:00
PMCR- 2010/04/01
CRDT- 2009/03/31 09:00
PHST- 2008/11/22 00:00 [received]
PHST- 2009/01/26 00:00 [revised]
PHST- 2009/01/26 00:00 [accepted]
PHST- 2009/03/31 09:00 [entrez]
PHST- 2009/03/31 09:00 [pubmed]
PHST- 2009/07/23 09:00 [medline]
PHST- 2010/04/01 00:00 [pmc-release]
AID - S1071-9164(09)00035-9 [pii]
AID - 10.1016/j.cardfail.2009.01.013 [doi]
PST - ppublish
SO  - J Card Fail. 2009 Apr;15(3):171-81. doi: 10.1016/j.cardfail.2009.01.013.