Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia

Daniel C. Javitt; Robert W. Buchanan; Richard S.E. Keefe; Robert Kern; Robert P. McMahon; Michael F. Green; Jeffrey Lieberman; Donald C. Goff; John G. Csernansky; Joseph P. McEvoy; Fred Jarskog; Larry J. Seidman; James M. Gold; David Kimhy; Karen S. Nolan; Deanna S. Barch; M. Patricia Ball; James Robinson; Stephen R. Marder

doi:10.1016/j.schres.2011.11.001

Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia

Daniel C. Javitt
, Robert W. Buchanan
, Richard S.E. Keefe
, Robert Kern
, Robert P. McMahon
, Michael F. Green
, Jeffrey Lieberman
, Donald C. Goff
, John G. Csernansky
, Joseph P. McEvoy
, Fred Jarskog
, Larry J. Seidman
, James M. Gold
, David Kimhy
, Karen S. Nolan
, Deanna S. Barch
, M. Patricia Ball
, James Robinson
, Stephen R. Marder

Research output: Contribution to journal › Article › peer-review

107 Scopus citations

Abstract

Background: Cognitive dysfunction is a key predictor of functional disability in schizophrenia. Davunetide (AL-108, NAP) is an intranasally administered peptide currently being developed for treatment of Alzheimer's disease and related disorders. This study investigates effects of davunetide on cognition in schizophrenia. Method: Sixty-three subjects with schizophrenia received davunetide at one of two different doses (5, 30. mg) or placebo for 12. weeks in a multicenter, double-blind, parallel-group randomized clinical trial. The MATRICS Consensus Cognitive Battery (MCCB) assessed cognitive effects. The UCSD Performance-based Skills Assessment (UPSA) and the Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity. Subjects continued their current antipsychotic treatment during the trial. Results: There were no significant differences in MCCB change between davunetide and placebo over the three treatment arms (p. =. .45). Estimated effect-size (d) values were .34 and .21 favoring the 5 and 30. mg doses vs. placebo, respectively. For UPSA, there was a significant main effect of treatment across study arms (p. =. .048). Between-group effect size (d) values were.74 and .48, favoring the 5 and 30. mg doses, respectively. No significant effects were observed on the SCoRS or on symptom ratings. No significant side effects or adverse events were observed. Conclusion: Davunetide was well tolerated. Effects of davunetide on MCCB-rated cognition were not significant relative to placebo. In contrast, a significant beneficial effect was detected for the UPSA. Based upon effect-size considerations, sample sizes of at least 45-50 subjects/group would be required to obtain significant effects on both MCCB and UPSA, providing guidance for continued clinical development in schizophrenia.

Original language	English
Pages (from-to)	25-31
Number of pages	7
Journal	Schizophrenia research
Volume	136
Issue number	1-3
DOIs	https://doi.org/10.1016/j.schres.2011.11.001
State	Published - Apr 2012

Keywords

Cognition
Microtubule
Neurite
Schizophrenia

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10.1016/j.schres.2011.11.001

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Javitt, D. C., Buchanan, R. W., Keefe, R. S. E., Kern, R., McMahon, R. P., Green, M. F., Lieberman, J., Goff, D. C., Csernansky, J. G., McEvoy, J. P., Jarskog, F., Seidman, L. J., Gold, J. M., Kimhy, D., Nolan, K. S., Barch, D. S., Ball, M. P., Robinson, J., & Marder, S. R. (2012). Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia. Schizophrenia research, 136(1-3), 25-31. https://doi.org/10.1016/j.schres.2011.11.001

@article{9821fbfbda6d414da029ba5865f8c01e,

title = "Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia",

abstract = "Background: Cognitive dysfunction is a key predictor of functional disability in schizophrenia. Davunetide (AL-108, NAP) is an intranasally administered peptide currently being developed for treatment of Alzheimer's disease and related disorders. This study investigates effects of davunetide on cognition in schizophrenia. Method: Sixty-three subjects with schizophrenia received davunetide at one of two different doses (5, 30. mg) or placebo for 12. weeks in a multicenter, double-blind, parallel-group randomized clinical trial. The MATRICS Consensus Cognitive Battery (MCCB) assessed cognitive effects. The UCSD Performance-based Skills Assessment (UPSA) and the Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity. Subjects continued their current antipsychotic treatment during the trial. Results: There were no significant differences in MCCB change between davunetide and placebo over the three treatment arms (p. =. .45). Estimated effect-size (d) values were .34 and .21 favoring the 5 and 30. mg doses vs. placebo, respectively. For UPSA, there was a significant main effect of treatment across study arms (p. =. .048). Between-group effect size (d) values were.74 and .48, favoring the 5 and 30. mg doses, respectively. No significant effects were observed on the SCoRS or on symptom ratings. No significant side effects or adverse events were observed. Conclusion: Davunetide was well tolerated. Effects of davunetide on MCCB-rated cognition were not significant relative to placebo. In contrast, a significant beneficial effect was detected for the UPSA. Based upon effect-size considerations, sample sizes of at least 45-50 subjects/group would be required to obtain significant effects on both MCCB and UPSA, providing guidance for continued clinical development in schizophrenia.",

keywords = "Cognition, Microtubule, Neurite, Schizophrenia",

author = "Javitt, \{Daniel C.\} and Buchanan, \{Robert W.\} and Keefe, \{Richard S.E.\} and Robert Kern and McMahon, \{Robert P.\} and Green, \{Michael F.\} and Jeffrey Lieberman and Goff, \{Donald C.\} and Csernansky, \{John G.\} and McEvoy, \{Joseph P.\} and Fred Jarskog and Seidman, \{Larry J.\} and Gold, \{James M.\} and David Kimhy and Nolan, \{Karen S.\} and Barch, \{Deanna S.\} and Ball, \{M. Patricia\} and James Robinson and Marder, \{Stephen R.\}",

note = "Funding Information: Funding for this study was provided by NIMH contract HHSN 27820044 1003C; PI: Steve Marder, M.D. The NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report, and in the decision to submit the paper for supervision. ",

year = "2012",

month = apr,

doi = "10.1016/j.schres.2011.11.001",

language = "English",

volume = "136",

pages = "25--31",

journal = "Schizophrenia research",

issn = "0920-9964",

number = "1-3",

}

Javitt, DC, Buchanan, RW, Keefe, RSE, Kern, R, McMahon, RP, Green, MF, Lieberman, J, Goff, DC, Csernansky, JG, McEvoy, JP, Jarskog, F, Seidman, LJ, Gold, JM, Kimhy, D, Nolan, KS, Barch, DS, Ball, MP, Robinson, J & Marder, SR 2012, 'Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia', Schizophrenia research, vol. 136, no. 1-3, pp. 25-31. https://doi.org/10.1016/j.schres.2011.11.001

TY - JOUR

T1 - Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia

AU - Javitt, Daniel C.

AU - Buchanan, Robert W.

AU - Keefe, Richard S.E.

AU - Kern, Robert

AU - McMahon, Robert P.

AU - Green, Michael F.

AU - Lieberman, Jeffrey

AU - Goff, Donald C.

AU - Csernansky, John G.

AU - McEvoy, Joseph P.

AU - Jarskog, Fred

AU - Seidman, Larry J.

AU - Gold, James M.

AU - Kimhy, David

AU - Nolan, Karen S.

AU - Barch, Deanna S.

AU - Ball, M. Patricia

AU - Robinson, James

AU - Marder, Stephen R.

N1 - Funding Information: Funding for this study was provided by NIMH contract HHSN 27820044 1003C; PI: Steve Marder, M.D. The NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report, and in the decision to submit the paper for supervision.

PY - 2012/4

Y1 - 2012/4

N2 - Background: Cognitive dysfunction is a key predictor of functional disability in schizophrenia. Davunetide (AL-108, NAP) is an intranasally administered peptide currently being developed for treatment of Alzheimer's disease and related disorders. This study investigates effects of davunetide on cognition in schizophrenia. Method: Sixty-three subjects with schizophrenia received davunetide at one of two different doses (5, 30. mg) or placebo for 12. weeks in a multicenter, double-blind, parallel-group randomized clinical trial. The MATRICS Consensus Cognitive Battery (MCCB) assessed cognitive effects. The UCSD Performance-based Skills Assessment (UPSA) and the Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity. Subjects continued their current antipsychotic treatment during the trial. Results: There were no significant differences in MCCB change between davunetide and placebo over the three treatment arms (p. =. .45). Estimated effect-size (d) values were .34 and .21 favoring the 5 and 30. mg doses vs. placebo, respectively. For UPSA, there was a significant main effect of treatment across study arms (p. =. .048). Between-group effect size (d) values were.74 and .48, favoring the 5 and 30. mg doses, respectively. No significant effects were observed on the SCoRS or on symptom ratings. No significant side effects or adverse events were observed. Conclusion: Davunetide was well tolerated. Effects of davunetide on MCCB-rated cognition were not significant relative to placebo. In contrast, a significant beneficial effect was detected for the UPSA. Based upon effect-size considerations, sample sizes of at least 45-50 subjects/group would be required to obtain significant effects on both MCCB and UPSA, providing guidance for continued clinical development in schizophrenia.

AB - Background: Cognitive dysfunction is a key predictor of functional disability in schizophrenia. Davunetide (AL-108, NAP) is an intranasally administered peptide currently being developed for treatment of Alzheimer's disease and related disorders. This study investigates effects of davunetide on cognition in schizophrenia. Method: Sixty-three subjects with schizophrenia received davunetide at one of two different doses (5, 30. mg) or placebo for 12. weeks in a multicenter, double-blind, parallel-group randomized clinical trial. The MATRICS Consensus Cognitive Battery (MCCB) assessed cognitive effects. The UCSD Performance-based Skills Assessment (UPSA) and the Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity. Subjects continued their current antipsychotic treatment during the trial. Results: There were no significant differences in MCCB change between davunetide and placebo over the three treatment arms (p. =. .45). Estimated effect-size (d) values were .34 and .21 favoring the 5 and 30. mg doses vs. placebo, respectively. For UPSA, there was a significant main effect of treatment across study arms (p. =. .048). Between-group effect size (d) values were.74 and .48, favoring the 5 and 30. mg doses, respectively. No significant effects were observed on the SCoRS or on symptom ratings. No significant side effects or adverse events were observed. Conclusion: Davunetide was well tolerated. Effects of davunetide on MCCB-rated cognition were not significant relative to placebo. In contrast, a significant beneficial effect was detected for the UPSA. Based upon effect-size considerations, sample sizes of at least 45-50 subjects/group would be required to obtain significant effects on both MCCB and UPSA, providing guidance for continued clinical development in schizophrenia.

KW - Cognition

KW - Microtubule

KW - Neurite

KW - Schizophrenia

UR - https://www.scopus.com/pages/publications/84857997678

U2 - 10.1016/j.schres.2011.11.001

DO - 10.1016/j.schres.2011.11.001

M3 - Article

C2 - 22169248

AN - SCOPUS:84857997678

SN - 0920-9964

VL - 136

SP - 25

EP - 31

JO - Schizophrenia research

JF - Schizophrenia research

IS - 1-3

ER -

Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia

Abstract

Keywords

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