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Adeno-Associated Viral Vector (Serotype 2)-Nerve Growth Factor for Patients With Alzheimer Disease: A Randomized Clinical Trial
Rafii MS, Tuszynski MH, Thomas RG, Barba D, Brewer JB, Rissman RA, Siffert J, Aisen PS et al.. JAMA neurology, 2018-07-01
Topic: Amyloid, tau and blood-test diagnosis
Importance Nerve growth factor (NGF) is an endogenous neurotrophic factor that prevents the death and augments the functional state of cholinergic neurons of the basal forebrain, a cell population that undergoes extensive degeneration in Alzheimer disease (AD). Objective To determine whether stereotactically guided intracerebral injections of adeno-associated viral vector (serotype 2)-nerve growth factor (AAV2-NGF) are well tolerated and exhibit preliminary evidence of impact on cognitive decline in mild to moderate AD-associated dementia. Design, setting, and participants In a multicenter phase 2 trial, 49 participants with mild to moderate AD were randomly assigned in a 1:1 ratio to receive stereotactically guided intracerebral injections of AAV2-NGF or sham surgery. Participants were enrolled between November 2009 and December 2012. Analyses began in February 2015. The study was conducted at 10 US academic medical centers. Eligibility required a diagnosis of mild to moderate dementia due to AD and individuals aged 55 to 80 years. A total of 39 participants did not pass screening; the most common reason was Mini-Mental State Examination scores below cutoff. Analyses were intention-to-treat. Interventions Stereotactically guided intracerebral injections of AAV2-NGF into the nucleus basalis of Meynert of each hemisphere or sham surgery. Main outcomes and measures Change from baseline on the Alzheimer's Disease Assessment Scale-cognitive subscale at month 24. Results Among 49 participants, 21 (43%) were women, 42 (86%) self-identified as white, and the mean (SD) age was 68 (6.4) years. AAV2-NGF was safe and well-tolerated through 24 months. No significant difference was noted between the treatment group and placebo on the primary outcome measure, the Alzheimer's Disease Assessment Scale-cognitive subscale (mean [SD] score, 14.52 [4.66] vs 9.11 [4.65], P = .17). Conclusions and relevance This multicenter randomized clinical trial demonstrated the feasibility of sham-surgery-controlled stereotactic gene delivery studies in patients with AD. AAV2-NGF delivery was well-tolerated but did not affect clinical outcomes or selected AD biomarkers. Pathological confirmation of accurate gene targeting is needed. Trial registration clinicaltrials.gov Identifier NCT00876863.
Key findings
- Results Among 49 participants, 21 (43%) were women, 42 (86%) self-identified as white, and the mean (SD) age was 68 (6.4) years.
- No significant difference was noted between the treatment group and placebo on the primary outcome measure, the Alzheimer's Disease Assessment Scale-cognitive subscale (mean [SD] score, 14.52 [4.66] vs 9.11 [4.65], P = .17).
- Conclusions and relevance This multicenter randomized clinical trial demonstrated the feasibility of sham-surgery-controlled stereotactic gene delivery studies in patients with AD.
Why it matters
In this phase 2 trial, AAV2-NGF did not show a significant difference from sham surgery on the primary cognitive outcome measure. The trial demonstrated the feasibility of sham-surgery-controlled stereotactic gene delivery, but not clinical benefit.
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Study details
- Study designclinical trial
- Participants49
- Evidence strengthHigh
How this study scored 69/100
Published in a leading specialty journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 66 of the 96 points we could judge it on, which is 69 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 1 / 4 | 49 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 5 / 7 | Cited 216 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 21.6 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 4 / 6 | Cited 13.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 3 / 4 | Cited 76 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29582053) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 66 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 66 of the 96 points we could judge it on is 69 out of 100. |
| Total | 69 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamaneurol.2018.0233
- PubMed: 29582053
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Rafii, M. S., Tuszynski, M. H., Thomas, R. G., Barba, D., Brewer, J. B., Rissman, R. A., et al. (2018). Adeno-Associated Viral Vector (Serotype 2)-Nerve Growth Factor for Patients With Alzheimer Disease: A Randomized Clinical Trial. JAMA neurology. https://doi.org/10.1001/jamaneurol.2018.0233
Vancouver
Rafii MS, Tuszynski MH, Thomas RG, Barba D, Brewer JB, Rissman RA, et al. Adeno-Associated Viral Vector (Serotype 2)-Nerve Growth Factor for Patients With Alzheimer Disease: A Randomized Clinical Trial. JAMA neurology. 2018. doi:10.1001/jamaneurol.2018.0233. PMID: 29582053.
BibTeX
@article{rafii2018-29582053,
author = {Rafii, M. S. and Tuszynski, M. H. and Thomas, R. G. and Barba, D. and Brewer, J. B. and Rissman, R. A. and Siffert, J. and Aisen, P. S. and others},
title = {{Adeno-Associated Viral Vector (Serotype 2)-Nerve Growth Factor for Patients With Alzheimer Disease: A Randomized Clinical Trial}},
journal = {JAMA neurology},
year = {2018},
doi = {10.1001/jamaneurol.2018.0233},
pmid = {29582053},
url = {https://doi.org/10.1001/jamaneurol.2018.0233}
}
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