Alkahest --- Sanket Rege (Researcher)

Chronokines

At Alkahest, we are decoding the plasma proteome to discover key proteins that increase or decrease with age, which we call chronokines.  We then interrogate the chronokines to find those which act as key checkpoint nodes of biological aging, whether driving beneficial pathways like homeostasis, tissue repair, neural functioning and stem cell regeneration, or those detrimental pathways that cause tissue damage, inflammation, and neurodegeneration.

From those with the most impact on biological function, we create transformative therapies that halt or reverse the harmful effects of aging in critical diseases and alleviate their devastating consequences afflicting patients around the world. Our simple, elegant approach capitalizes on the body’s natural regulatory and communication mechanism: the plasma proteome.

The potential influence of chronokines in diseases of aging has inspired our therapeutic approach, which has so far delivered three candidates into Phase II clinical trials.  In preclinical studies, Alkahest scientists demonstrated that our therapeutic targets activate molecular signaling pathways in older animals that include increased tissue regeneration, reduced age-related cognitive impairment, reduced neuroimmune activation, increased memory function.

Our current clinical trials are testing our therapeutic approaches for a range of age-related medical conditions, including Alzheimer’s disease, Parkinson’s disease, Age-Related Macular Degeneration, post-surgical recovery and others.

Tony Wyss-Coray

Tony Wyss-Coray, D. H. Chen Distinguished Professor of Neurology and Neurological Sciences at Stanford University, is the Co-Director of the Stanford Alzheimer’s Disease Research Center, and Senior Research Career Scientist at the Palo Alto VA. His lab studies brain aging and neurodegeneration with a focus on age-related cognitive decline and Alzheimer’s disease.

The Wyss-Coray research team discovered that circulatory blood factors can modulate brain structure and function and factors from young organisms can rejuvenate old brains. These findings were voted 2nd place Breakthrough of the Year in 2014 by Science Magazine and presented in talks at Global TED, the World Economic Forum, and Google Zeitgeist.

Wyss-Coray is the recipient of an NIH Director’s Pioneer Award, a Zenith Award from the Alzheimer’s Association, a NOMIS Foundation Award, an inventor on multiple patents, and was selected by TIME Magazine to “The Health Care 50” as one of the most influential people transforming healthcare in 2018.

AKST4290

AKST4290

AKST4290 is an orally administered CCR3 inhibitor that blocks the action of eotaxin, an immunomodulatory protein that increases as humans age and with specific age-related diseases. By targeting eotaxin and its downstream effects, AKST4290 may reduce the hallmark inflammation and neovascularization of AMD while also acting more broadly to reduce inflammation associated with many other age-related diseases.  The molecule is currently being tested in Parkinson’s Disease with additional indications being explored.   

Alkahest

Alkahest is a clinical stage biopharmaceutical company dedicated to discovering and developing treatments for neurodegenerative and age-related diseases with transformative therapies targeting the aging plasma proteome. The Alkahest pipeline includes multiple therapeutic candidates ranging from selected plasma fractions to protein-targeted interventions which aim to slow the detrimental biological processes of aging. Alkahest is developing novel plasma-based therapies in collaboration with Grifols, a global healthcare company and leading producer of plasma therapies.

Plasma-based strategies for brain aging

Woman running on the treadmill

Abstract

Age is the primary risk factor for the vast majority of disorders, including neurodegenerative diseases impacting brain function. Whether the consequences of aging at the biological level can be reversed, or age-related changes prevented, to change the trajectory of such disorders is thus of extreme interest and value.

Studies using young plasma, the acellular component of blood, have demonstrated that aging is malleable, with the ability to restore functions in old animals. Fascinatingly, this functional improvement is even observed in the brain, despite the blood-brain barrier, indicating that peripheral sources can effectively impact central sites leading to clinically relevant changes such as enhancement of cognitive function.

A plasma-based approach is also attractive as aging is inherently complex, with an array of mechanisms dysregulated in diverse cells and organs throughout the body leading to disturbed function. Plasma, containing a natural mixture of components, has the ability to act multimodally, modulating diverse mechanisms that can converge to change the trajectory of age-related diseases.

Here we review the evidence that plasma modulates aging processes in the brain and consider the therapeutic applications that derive from these observations. Plasma and plasma-derived therapeutics are an attractive translation of this concept, requiring critical consideration of benefits, risks, and ethics. Ultimately, knowledge derived from this science will drive a comprehensive molecular understanding to deliver optimized therapeutics. The potential of highly differentiated, multimodal therapeutics for treatment of age-related brain disorders provides an exciting new clinical approach to address the complex etiology of aging.

FULL TEXT: Neurotherapeutics