A LETTER FROM ARNON

At Alector, we do not view diseases of aging as immutable facts.  We are on a mission to slow down their progression and prevent their occurrence.  We envision a world where each individual retains his or her full brain function and cognitive faculties throughout life — a world where dementia and neurodegeneration are illnesses of the past just as smallpox, diphtheria, rubella, and polio have become.

Since the early 20th century, the root cause of neurodegeneration has been considered to be misfolded proteins such as amyloid-beta plaques and TAU tangles in Alzheimer’s disease, alpha-synuclein in Parkinson’s disease and TDP-43 in FTD and amyotrophic lateral sclerosis.  Other pathologies that typify neurodegeneration, including the dysfunction and destruction of neuronal connections, the accelerated death of nerve cells, and the dysfunction of the brain support cells, were thought to be consequences of these misfolded proteins.

Since our founding five years ago, we have challenged this widely held belief.  We made the case that multiple pathologies that typify neurodegeneration become autonomous of each other at early disease stages, and for therapeutic purposes, these pathologies should be viewed as independent causes of the disorder.  With this understanding, we searched for an underlying biological process that these pathologies share.  Discoveries on the genetic underpinning of neurodegeneration and on the functions of the brain immune system led us to conclude that these parallel pathologies are primarily caused by a dysfunctional brain immune system.

The specific scientific advances that enabled our conclusion were: (1) the identification of harmful genetic mutations that increase the risk of developing Alzheimer’s disease; (2) the revelation that the majority of these mutations are in proteins that regulate the brain immune system; and (3) the findings that the immune cells in the brain are responsible for a myriad of functions, which include compacting and disposing of misfolded proteins, the formation, maintenance and function of neuronal connections, and the survival and function of the brain’s support cells and neurons.

Since most neurodegenerative diseases are diseases of aging, we postulated that the brain immune cells lose their competence with time and are no longer able to support normal brain function or to repair avoidable brain pathologies.  In futile attempts to act, the senescing immune cells may further exacerbate the disease by secreting toxic immune mediators and by indiscriminate scavenging.

With this understanding, we devoted the last five years to the development of novel therapeutics that harness the brain’s immune system to treat neurodegeneration.  We have advanced one of our product candidates into clinical trials and plan to test the impact of a total of four of our product candidates in patients suffering from Alzheimer’s disease and FTD in 2019.

I have invested much of my 35 years in the biotech industry into building teams that develop innovative therapeutics in neuroscience.  During my 16 years with Genentech, I built a team that discovered multiple neuronal survival factors and receptors in order to prevent degenerative nerve cell death.  As the Founder, President, and Chief Science Officer of Rinat Neuroscience, my team and I discovered clinical antibodies designed to target misfolded proteins.  As a Co-Founder and the former Chief Executive Officer of Annexon Biosciences, my team and I developed clinical antibodies that prevent destruction of neuronal connections.  I am a named inventor on over 350 issued patents and patent applications and am an author on over 100 peer reviewed publications.  My teams and I discovered the target for the approved cancer drug, Erivedge, and were responsible for the development of the pain drug candidate, tanezumab, and the approved migraine antibody drug, AJOVY.  Our work at Alector is based upon our understanding of the basic biology of degenerative brain disorders and how to translate this understanding into effective therapeutics.

The World Health Organization estimates that up to 1 billion people are affected by neurological disorders.  There are currently over 50 million people with neurodegeneration worldwide, with over 10 million new cases each year.  The Alzheimer’s Association projected that the cumulative total cost of Medicare and Medicaid for individuals living with Alzheimer’s disease will total $750 billion by 2050 in the United States alone, an increase of over 300% from projected 2018 spending levels.

Degenerative brain disorders are among the last medical frontiers that have yet to be conquered.  If we are successful in our mission to treat neurodegeneration, Alector will have a profound impact on humanity. 

Best Regards,
Arnon Rosenthal, Ph.D.
Co-Founder and Chief Executive Officer