Experimental therapies bind to Parkinson’s-associated proteins
Attralus is developing treatments that would bind to proteins across multiple neurodegenerative diseases
AT-04 and AT-07, experimental therapies Attralus is developing to treat Parkinson’s disease and other neurodegenerative disorders, are able to potently bind to several proteins that form toxic clumps in these conditions.
That’s according to new data shared at the AD/PD 2023-International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders, in the presentation “Development of brain shuttle enabled AT-04, a novel peptibody that binds neuropathologic fibrillar aggregates.”
“While most therapies in development target individual [disease-associated proteins], such as [amyloid-beta], tau, or [alpha-synuclein], AT-04 and AT-07 target all [these proteins] in each patient and have the potential to transform the lives of patients living with neurodegenerative disorders,” Gregory Bell, MD, chief medical officer of Attralus, said in a company press release.
Multiple neurodegenerative diseases such as Parkinson’s are marked by toxic clumps of proteins that form in and around brain cells, which are thought to drive the diseases.
Toxic aggregates of the alpha-synuclein protein are associated with Parkinson’s, whereas amyloid-beta and tau protein clumps have been implicated in the development and progression of Alzheimer’s disease, although, there is some overlap of these aggregates across diseases.
While there are notable differences in the structure and function of these proteins, they all tend to form specific type of insoluble, fibrous clumps called amyloid deposits or amyloid fibrils. Attralus is developing therapies to bind to all types of them.
AT-04 contains an amyloid-binding peptide, or protein fragment, attached to a piece of a human antibody. The idea is the peptide will stick to toxic amyloid in the brain and then the antibody fragment will cue the immune system to remove it.
AT-07, which is being developed with Ossianix, contains AT-04 alongside Ossianix’s proprietary TXP1 brain shuttle, a molecule designed to let the therapy more effectively get into the brain. This brain shuttle is based on a single domain variable immunoglobulin new antigen receptor (VNAR) antibody.
Newly presented data showed AT-04 binding to toxic clumps of alpha-synuclein, amyloid-beta, and tau at extremely low (subnanomolar) concentrations. It also showed the ability to bind to amyloid-beta aggregates in a mouse model of Alzheimer’s. And AT-04 and AT-07 were both able to bind to toxic amyloid-beta clumps in brain tissue from Alzheimer’s patients. AT-07 led to 10 times higher levels of the active medication in the brain in mouse experiments.
“We are encouraged to see additional data demonstrating the potent binding of [amyloid-beta], tau, and [alpha-synuclein] fibrils, amyloids common to neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Lewy body diseases,” Bell said. “We are excited to further explore the potential of AT-04 in neurodegenerative disorders alone and in combination with the variable immunoglobulin new antigen receptors (VNAR) antibody-based Brain Shuttle in collaboration with Ossianix (AT-07).”