Science
Toward Remyelinating Therapeutics
The Adams Lab builds on Drew's unique interdisciplinary training, which spans organic chemistry, chemical biology, entrepreneurship, and industry-led drug discovery. The lab’s specialized expertise and drug discovery instrumentation have led to impactful discoveries at Case Western Reserve University in multiple disease areas.
An early focus of the lab entailed elucidating cellular mechanisms by which small molecules promote the formation of oligodendrocytes, the specialized cell that produces myelin in the brain. Loss of oligodendrocytes underlies many neurological diseases, including multiple sclerosis and pediatric leukodystrophies. Specialized brain stem cells ('oligodendrocyte progenitor cells') are known to have a limited capacity to replace lost oligodendrocytes, but this innate repair process can be overwhelmed in the context of disease. Future 'remyelinating therapeutics' that kickstart the formation of new oligodendrocytes represent a regenerative medicine approach that may accelerate the regeneration of functional myelin and have therapeutic impact in these debilitating diseases.
The Adams Lab, in close collaboration with Prof. Paul Tesar (Case Western Reserve University), provided a new understanding of how drug candidates impact brain stem cells to enhance myelin repair. Our landmark paper, published July 2018 in Nature, detailed how dozens of molecules identified by multiple labs shared the ability to inhibit specific cellular enzymes that help make cholesterol. As a result, the sterol substrates of these enzymes accumulate and signal to promote the formation of new myelin. This new insight, which powerfully unified results obtained by labs across the globe, pointed toward new drug targets, new potent drug leads, and new sterol biomarkers to guide the future development of remyelinating therapeutics.
Since 2018, Drew has pursued both the mechanistic and therapeutic implications of this discovery. Subsequent papers from the Adams Lab highlighted additional cholesterol pathway enzymes whose inhibition promotes oligodendrocyte formation, ultimately leading to the conclusion that nearly all molecules in the field functioned by targeted cholesterol biosynthesis (Sax, ACS Chem. Biol., 2022, and reviewed in Caprariello, Nature Chemical Biology, 2022).
Additionally, Drew became a Co-Founder of Convelo Therapeutics, a Cleveland-based startup launched in 2017. In 2018, while maintaining his lab at CWRU, Drew formally joined Convelo as VP of Discovery and helped navigate Convelo’s subsequent research partnership with Genentech/Roche, announced in 2019. In 2020 Drew was promoted to Project Team Co-Lead, enabling him to lead both Convelo’s 15-scientist team and its communications with Genentech. Drew’s ongoing experience with Convelo has provided an extraordinary education in entrepreneurship and world-class drug discovery that now informs projects emerging from his lab at CWRU.
Current work in the Adams Lab seeks to further understand how sterol signaling mechanisms regulate oligodendrocyte formation but also seeks to establish novel therapeutic targets in disease states beyond multiple sclerosis, including other autoimmune diseases and cancer.
An early focus of the lab entailed elucidating cellular mechanisms by which small molecules promote the formation of oligodendrocytes, the specialized cell that produces myelin in the brain. Loss of oligodendrocytes underlies many neurological diseases, including multiple sclerosis and pediatric leukodystrophies. Specialized brain stem cells ('oligodendrocyte progenitor cells') are known to have a limited capacity to replace lost oligodendrocytes, but this innate repair process can be overwhelmed in the context of disease. Future 'remyelinating therapeutics' that kickstart the formation of new oligodendrocytes represent a regenerative medicine approach that may accelerate the regeneration of functional myelin and have therapeutic impact in these debilitating diseases.
The Adams Lab, in close collaboration with Prof. Paul Tesar (Case Western Reserve University), provided a new understanding of how drug candidates impact brain stem cells to enhance myelin repair. Our landmark paper, published July 2018 in Nature, detailed how dozens of molecules identified by multiple labs shared the ability to inhibit specific cellular enzymes that help make cholesterol. As a result, the sterol substrates of these enzymes accumulate and signal to promote the formation of new myelin. This new insight, which powerfully unified results obtained by labs across the globe, pointed toward new drug targets, new potent drug leads, and new sterol biomarkers to guide the future development of remyelinating therapeutics.
Since 2018, Drew has pursued both the mechanistic and therapeutic implications of this discovery. Subsequent papers from the Adams Lab highlighted additional cholesterol pathway enzymes whose inhibition promotes oligodendrocyte formation, ultimately leading to the conclusion that nearly all molecules in the field functioned by targeted cholesterol biosynthesis (Sax, ACS Chem. Biol., 2022, and reviewed in Caprariello, Nature Chemical Biology, 2022).
Additionally, Drew became a Co-Founder of Convelo Therapeutics, a Cleveland-based startup launched in 2017. In 2018, while maintaining his lab at CWRU, Drew formally joined Convelo as VP of Discovery and helped navigate Convelo’s subsequent research partnership with Genentech/Roche, announced in 2019. In 2020 Drew was promoted to Project Team Co-Lead, enabling him to lead both Convelo’s 15-scientist team and its communications with Genentech. Drew’s ongoing experience with Convelo has provided an extraordinary education in entrepreneurship and world-class drug discovery that now informs projects emerging from his lab at CWRU.
Current work in the Adams Lab seeks to further understand how sterol signaling mechanisms regulate oligodendrocyte formation but also seeks to establish novel therapeutic targets in disease states beyond multiple sclerosis, including other autoimmune diseases and cancer.