Safety study of BT-267 Parkinson’s therapy begins dosing volunteers
Brenig planning next clinical trials in patients with idiopathic disease
A clinical trial testing the safety and tolerability of Brenig Therapeutics‘ BT-267, a potential disease-modifying therapy for Parkinson’s due to an unknown cause — known as idiopathic — or disease associated with LRRK2 gene mutations, has begun dosing healthy volunteers.
Following this initial assessment — the first-in-human trial of the therapy candidate — Brenig plans to start studies in patients with idiopathic Parkinson’s, according to a company press release.
“Preclinical data underscores the potential of BT-267 as [a] best-in-class LRRK2 inhibitor, confirming a superior safety profile,” the company stated, adding that the experimental Parkinson’s therapy “benefits from cutting-edge computer-aided drug design.”
Parkinson’s therapy candidate designed to block LRRK2 enzyme
A hallmark feature of Parkinson’s disease is the dysfunction and death of dopaminergic nerve cells, neurons that produce a key brain chemical messenger called dopamine. This leads to a range of motor symptoms, including tremors, rigidity, and slowness of movements, as well as nonmotor symptoms such as cognitive impairment, depression, and sleeping issues.
In most patients, the cause of Parkinson’s is idiopathic, or can not be specifically identified. However, 5% to 10% of cases result from mutations in a single gene.
Among the most common genetic causes of Parkinson’s are mutations in the LRRK2 gene, which provides instructions to produce the leucine-rich repeat kinase 2, also known as LRRK2. An overactive LRRK2 enzyme is thought to contribute to Parkinson’s by impairing a cell’s ability to get rid of damaging material. LRRK2 is also implicated in regulating the function of mitochondria, which are cellular components responsible for producing energy.
BT-267 is a small molecule inhibitor of LRRK2 that’s designed to effectively and selectively target this enzyme while minimizing off-target effects. The compound was designed using artificial intelligence, in collaboration with Expert Systems, a drug discovery accelerator platform, to allow sustained and high exposure in the brain and limited exposure elsewhere, according to Brenig.
“Brenig’s advanced approach to predictive biomarkers may help position BT-267 candidate as a promising disease-modifying therapy for Parkinson’s, including idiopathic cases that lack known genetic drivers,” the release stated.
In preclinical assessments, the treatment showed a good safety profile, with little or no visible lung and kidney abnormalities in GLP toxicology studies at the highest tested doses. GLP, short for Good Laboratory Practices, ensures regulatory compliance, integrity, quality, and reliability of products in nonclinical studies.
In addition, testing showed the therapy was present at higher levels in the cerebrospinal fluid, or CSF — the fluid that bathes the brain and spinal cord — than in the liquid component of blood. Specifically, it had a high CSF to plasma unbound ratio, according to the company.
The development of BT-267 is supported by $65 million obtained in a Series A funding round led by New Enterprise Associates. A Series A financing round is often the first round of venture money raised by a company.
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