Aperture to advance potential treatment for ALS and dementia
Company to move APRTX-001 toward preclinical studies
- Aperture is advancing APRTX-001 as a treatment for ALS and neurodegenerative diseases.
- APRTX-001 aims to reduce levels of CD33, a protein on microglia linked to neuroinflammation.
- The therapy is in preclinical studies to determine its safety and pharmacology.
Aperture Therapeutics has selected APRTX-001 as its lead candidate to treat amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases.
The therapy is designed to reduce the levels of CD33, a receptor protein on the surface of microglia — the resident immune cells of the central nervous system (CNS, or the brain and spinal cord) — that plays a crucial role in regulating microglial function and neuroinflammation.
The company is advancing through investigational new drug (IND)-enabling studies to determine APRTX-00’s safety and pharmacological properties in preclinical models. This type of study is needed to advance into clinical studies in humans.
“Although CD33 has long been recognized as an important regulator of neuroinflammation in neurodegenerative disease, prior attempts to drug this pathway with small molecules or antibodies have failed due to modality-associated challenges and poor translation in preclinical models, underscoring the need for a more precise RNA-targeting approach,” Martin Jacko, PhD, Aperture’s founder and CEO, said in a company press release. “By directly modulating CD33 at the RNA level, APRTX-001 overcomes these historical barriers with a precision approach grounded in human genetics.”
People with neurodegenerative conditions such as ALS, frontotemporal dementia, and Alzheimer’s disease have elevated levels of CD33. Certain naturally occurring genetic variants that impair CD33 production or function reduce neuroinflammation and make people less likely to develop neurodegenerative diseases.
Focus on CD33
APRTX-001 is an antisense oligonucleotide (ASO) designed to reduce the levels of CD33. An ASO contains a short strand of genetic material that binds to a gene’s messenger RNA, the template molecule needed for protein production, and target it for destruction.
The experimental treatment is expected to suppress CD33 production and replicate the protective role of certain CD33 variants. The company is currently developing it to treat ALS and frontotemporal dementia, with the potential for subsequent development for Alzheimer’s.
Aperture’s treatment development process is based on genetic variants known to protect against neurodegeneration. Artificial intelligence is then used to guide the development of therapy candidates, which are tested in animals engineered to produce the human version of target molecules.
The company developed a mouse model that produces human CD33 to test CD33-targeting molecules, enabling the selection of APRTX-001 as the most promising candidate for easy translation into clinical use.
The discovery and optimization of CD33-targeting molecules was supported by funding from the National Institute of Neurological Disorders and Stroke.
Aperture is also advancing therapy programs targeting other neuroinflammatory and neurodegenerative mechanisms and developing a technology to deliver neuroinflammation-targeting therapies specifically to microglia.
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