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

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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
Externally published	Yes

Bibliographical 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.

Keywords

Cognition
Microtubule
Neurite
Schizophrenia

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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

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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 = "אנגלית",

volume = "136",

pages = "25--31",

journal = "Schizophrenia Research",

issn = "0920-9964",

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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

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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

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ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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