Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Preclinical Development: Overview01:28

Preclinical Development: Overview

5.7K
Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...
5.7K
Clinical Trials: Overview01:11

Clinical Trials: Overview

4.5K
Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
4.5K
Drug Discovery: Overview01:26

Drug Discovery: Overview

10.9K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
10.9K
Drug Administration and Therapy Phases: Overview01:26

Drug Administration and Therapy Phases: Overview

1.1K
Drugs, the chemical agents used in diagnosing, treating, or preventing diseases, undergo a four-phase process of development: pharmaceutic, pharmacokinetics, pharmacodynamics, and therapeutic.
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
1.1K
In Vitro Drug Release Testing: Overview, Development and Validation01:10

In Vitro Drug Release Testing: Overview, Development and Validation

269
In vitro dissolution and drug release tests assess how quickly and how much of a drug is released from its dosage form into an aqueous medium under standardized laboratory conditions. These tests are essential tools in pharmaceutical development and quality assurance, offering insight into the drug's performance before clinical use.During formulation development, dissolution testing identifies incomplete or inconsistent drug release issues. It also supports decisions on selecting the optimal...
269
Drug Regulation01:25

Drug Regulation

2.7K
Drug regulation encompasses the management of drug usage by evaluating its safety and efficacy through assessments conducted by regulatory authorities. Regrettably, the history of drug regulation is marred by several catastrophic events. One such incident is the Elixir Sulfanilamide tragedy, in which the toxic compound diethyl glycol was included in a sweet-tasting medication, leading to numerous fatalities. This event prompted the enactment of the Food, Drug, and Cosmetic Act in 1938. Under...
2.7K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

AAVrh.10hFXN Gene Therapy for the Cardiomyopathy of Friedreich Ataxia: A Nonrandomized Clinical Trial.

JAMA cardiology·2026
Same author

Evaluating the Duke Iterative Cognitive Examination Against the Montreal Cognitive Assessment: Validity and Clinical Utility.

Neurology. Clinical practice·2026
Same author

Olfactory cleft biopsy analysis of Alzheimer's disease pathobiology across disease stages.

Nature communications·2026
Same author

Cerebrospinal fluid amyloid-β 42/40 ratio is associated with ganglion cell-inner plexiform layer thinning in individuals with and without amyloid pathology.

Journal of Alzheimer's disease : JAD·2026
Same author

Higher spatial resolution diffusion-weighted imaging improves characterization of white matter disconnection in Alzheimer's disease.

Imaging neuroscience (Cambridge, Mass.)·2026
Same author

Prime Editing of Alzheimer's Disease High-Risk APOE4 Allele by Brain-Directed Adeno-Associated Virus Vectors.

Human gene therapy·2025
Same journal

Unveiling the procoagulant state in Alzheimer's disease: A novel PET imaging strategy.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Estimated labor market outcomes of people progressing from preclinical to early-stage Alzheimer's disease in the United States.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Amyloid exacerbates tau and alpha-synuclein pathologies, behavioral impairments, and neuroinflammation in a mixed dementia model.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Multimorbidity burden and patterns associated with DeepBrainNet-derived brain-age gap in dementia-free older adults: A community-based study.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Reply to "Shifting the emphasis of brain health literacy from individuals to systems to reduce inequalities".

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Shifting the emphasis of brain health literacy from individuals to systems to reduce inequalities.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
See all related articles

Related Experiment Video

Updated: Jan 7, 2026

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
05:10

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System

Published on: December 11, 2016

10.1K

Drug Development.

Kim G Johnson1, Michael Kaplitt2, Stephen Kaminsky2

  • 1Duke University School of Medicine, Durham, NC, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

LX1001 gene therapy shows promise for APOE4 homozygotes with Alzheimer's disease. The treatment was safe and well-tolerated, reducing key Alzheimer's biomarkers.

More Related Videos

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
08:04

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing

Published on: May 11, 2021

3.3K
Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells
05:45

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells

Published on: October 10, 2025

446

Related Experiment Videos

Last Updated: Jan 7, 2026

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
05:10

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System

Published on: December 11, 2016

10.1K
In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
08:04

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing

Published on: May 11, 2021

3.3K
Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells
05:45

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells

Published on: October 10, 2025

446

Area of Science:

  • Neuroscience
  • Genetics
  • Pharmacology

Background:

  • APOE4 homozygotes experience accelerated cognitive decline in Alzheimer's disease (AD).
  • APOE2 is a protective variant associated with reduced AD risk and slower decline.
  • LX1001 is an investigational gene therapy using AAVrh.10hAPOE2 to deliver the APOE2 gene.

Purpose of the Study:

  • To evaluate the safety and tolerability of LX1001 in APOE4 homozygotes with AD.
  • To assess the gene therapy's ability to convert the APOE4/4 genotype to APOE2/4 in the central nervous system.

Main Methods:

  • Phase 1/2, dose escalation study (NCT03634007) in four ascending single-dose cohorts.
  • LX1001 administered into cerebrospinal fluid (CSF) at the craniocervical junction.
  • Participants: APOE4 homozygotes (≥50 years) with mild cognitive impairment to moderate dementia, positive amyloid PET, and consistent AD CSF biomarkers.

Main Results:

  • Fifteen participants were dosed; 50% mild cognitive impairment, 14% mild dementia, 36% moderate dementia.
  • LX1001 was generally safe and well-tolerated; no amyloid-related imaging abnormalities observed.
  • Dose-dependent APOE2 expression in CSF; stabilization in CSF Aβ42/40 and amyloid PET; reduction in CSF t-tau, p-tau, and Tau PET.

Conclusions:

  • LX1001 is the first gene therapy investigated for APOE4 homozygotes with AD.
  • Data suggest LX1001 is safe and well-tolerated.
  • LX1001 demonstrated reduction in CSF tau biomarkers and Tau PET, correlated with cognitive decline.