Our Science

We leverage human genetics

At Alector we find solutions that will work for patients. We follow the science and don’t subscribe to dogma.

Decoding neurodegeneration

Neurodegenerative diseases are incurable and debilitating conditions that result in progressive death of nerve cells.

Symptoms of neurodegeneration

Trouble retrieving memories
Inability to recognize common things
Difficulty thinking and understanding
Mental confusion
Loss of motor function and coordination

We are deploying immuno-neurology as a therapeutic strategy for the treatment of neurodegeneration.

Significant scientific evidence that has emerged in the last decade has shown us that the immune system is involved in the development of neurodegenerative diseases.

Research rooted in genetics.

A deep understanding of human genetics and recent evidence generated in genome wide association studies led to our immuno-neurology therapeutic hypothesis.

Human genetic evidence supports the importance of the interaction between the brain and the innate immune system. For example, twenty-two of the top 25 risk genes for Alzheimer’s disease regulate immune function in the brain.

At Alector, our programs come from translating genetic insights into target and drug discovery.

Learn about our research

We leverage biomarkers to increase our efficiency and accelerate our clinical development.

We identify and employ molecular biomarkers, assays and imaging techniques tailored to our product candidates to confirm target engagement and quantify their therapeutic impact.

These efforts allow us to potentially obtain clinical data earlier than would be typically expected using traditional clinical measures and may increase our programs’ chances of success.

Fluid biomarkers

 

Fluid biomarkers can include proteins, lipids or nucleotides (RNA or DNA) in any of the body fluids and can be used as safety markers, assessing target engagement, and quantifying therapeutic efficacy. In our studies, we measure fluid biomarkers in blood and in cerebrospinal fluid (CSF).

Fluid biomarker example:
Neurofilament light chain

Neurofilament light chain (NfL) is a component protein of the neuron cytoskeleton that provides structural support for neurons and plays a number of important roles in intracellular transport of proteins within the axons. When nerve cells are damaged, NfL is released into the CSF and into the blood. Thus, NfL protein can serve as an indicator of neuronal loss and disease progression in neurological disorders, such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD).

Imaging biomarkers

 

Imaging biomarkers can be used to measure the structure and function of the brain as well as protein aggregates in the brain known to be involved in disease. In our studies we leverage a variety of imaging tools to assess brain integrity.

Imaging biomarker example:
Volumetric MRI

Volumetric MRI (vMRI) is a non-invasive brain imaging technique used to measure the volume and structural integrity of specific regions of the brain. People with neurodegenerative diseases such as AD or FTD have an increased annual rate of brain volume loss compared to age-matched individuals with healthy brains. vMRI can be used to measure the rate of brain volume loss and assess if the atrophy rate decreases in response to treatment with a product candidate.

Alector’s Approach

Leverage human genetics and insights into neurology

Create a broad portfolio of targets and programs

Rapidly move programs from discovery into clinical trials

Our Pipeline

Program

Mechanism

Stages

Research

Pre-clinical

Phase 1

Phase 2

Phase 3

Commercial Rights

AL001

Our product candidate, AL001, is a humanized recombinant monoclonal antibody that is intended to be delivered by intravenous, peripheral infusion to the bloodstream to increase the levels of PGRN in the brains of FTD-GRN patients. AL001 functions by shutting down the SORT1 degradation mechanism for PGRN and increasing the circulating half-life of the functional PGRN in the brain. AL001 received orphan drug designation from the FDA for the treatment of FTD in 2018.

Our AL001 development program is focused on modulating levels of PGRN, a key regulator of microglia function in the brain with strong genetic links to FTD and other neurodegenerative disorders. Healthy individuals carry two copies of PGRN that function together to produce healthy levels of PGRN throughout the body. Mutations in both copies of the PGRN gene lead to a neurodegenerative disease called neuronal ceroid lipofuscinosis, which is typified by childhood dementia, vision loss, and epilepsy. Mutations in a single copy of PGRN lead to a drop of between 50% and 70% in the level of PGRN and consequently lead to the development of FTD with greater than 90% probability. Moreover, large scale human genetic studies have shown that mutations in the gene for PGRN, which leads to a more modest decrease in the level of PGRN, increases the risk for Alzheimer’s disease and Parkinson’s disease, making PGRN a significant risk gene for these disorders as well.

Human and mouse genetic studies have identified SORT1 as a major negative regulator of PGRN levels in plasma and the brain. SORT1 is a sorting receptor on the cell surface and on the endoplasmic reticulum-Golgi apparatus within the cell. SORT1 binds to extracellular PGRN in the plasma and brain and transports it into the cells for degradation by the lysosome resulting in decreasing levels of extracellular PGRN.

AL001 has been tested in humans and has successfully demonstrated it is able to increase PGRN levels back to normal range in both symptomatic and pre-symptomatic FTD-GRN patients. AL001 was shown to be generally safe and well tolerated in healthy volunteers and FTD-GRN patients. The program is currently in Phase 2.

Mechanism

Progranulin

Indication

Frontotemporal Dementia with a granulin mutation (FTD-GRN)
Frontotemporal Dementia with a C9orf72 mutation (FTD-C9orf72)

Stage of Development

Phase 2
Progranulin
Frontotemporal Dementia with a granulin mutation
Frontotemporal Dementia with a C9orf72 mutation
Progranulin
Neurology
TREM 2
Alzheimer's Disease
SIGLEC 3
Alzheimer's Disease
MS4A4A
Alzheimer's Disease
Immuno-Neurology / Immuno-Oncology
ADP012
ADP016
ADP017
ADP023
ADP026
ADP122
ADP008
ADP009
ADP022

Research

Pre-clinical

Phase 1

Phase 2

Phase 3

AL001

Progranulin
Frontotemporal Dementia with a granulin mutation
Phase 2
Frontotemporal Dementia with a C9orf72 mutation
Phase 2

AL101

Progranulin Neurology
Neurology
Phase 1

AL002

TREM 2 Alzheimer's Disease
Alzheimer's Disease
Phase 1

AL003

SIGLEC 3 Alzheimer's Disease
Alzheimer's Disease
Phase 1

AL014

MS4A4A Alzheimer's Disease
Alzheimer's Disease
Pre-clinical

9 Candidates

Immuno-Neurology / Immuno-Oncology
ADP012
Research
ADP016
Research
ADP017
Research
ADP023
Research
ADP026
Research
ADP122
Research
ADP008
Research
ADP009
Research
ADP022
Research

About us

We envision a world where each individual retains his or her full brain function and cognitive faculties throughout life.

Learn our Approach

We envision a world where each individual retains his or her full brain function and cognitive faculties throughout life.