AI-designed Parkinson’s therapy prepares to move to clinical trials
Insilico says it will file IND application with FDA by year-end
An oral anti-inflammatory therapy for Parkinson’s disease developed using artificial intelligence (AI) may be nearing clinical trials.
Insilico Medicine said it plans to seek clearance later this year from the U.S. Food and Drug Administration (FDA) to advance the therapy, ISM8969, into human trials. The company said its investigational new drug (IND) application will be based on results from completed preclinical studies that showed that ISM8969 restored some motor skills in a mouse model of Parkinson’s.
“We are thrilled to reach the milestone of IND-enabling [study] completion, as it marks the beginning of clinical validation for ISM8969,” Alex Zhavoronkov, PhD, founder, CEO, and chief business officer at Insilico, said in a company press release. “The anti-inflammation strategy against Parkinson’s disease has never before passed the whole process of clinical validation, so the progress of ISM8969 is indeed encouraging.”
Parkinson’s is caused by the progressive death of nerve cells, or neurons, that communicate using the signaling molecule dopamine. This can lead to tremor, slowed movement, and other motor symptoms, as well as nonmotor symptoms.
Although there are several available Parkinson’s treatments, these tend to focus on easing symptoms rather than targeting the biological processes at play in the disease. “Current treatments often cause adverse effects that limit long-term use and do not address the underlying progression of the disease,” said Feng Ren, PhD, co-CEO and chief scientific officer of Insilico.
AI could be ‘game changer’
“These positive data further strengthen our belief in the potential of ISM8969, as well as the reliability of AI-driven drug discovery method, in the new field of [central nervous system] diseases,” Ren said. The central nervous system comprises the brain and spinal cord.
Neuronal damage and death can trigger neuroinflammation, which can in turn cause more tissue damage. One strategy for influencing Parkinson’s progression involves changing the body’s inflammatory response.
The NLRP3 inflammasome, a multiprotein complex that is key in sensing infections and damage and that works together to trigger inflammation, has been reported to drive inflammatory neurotoxicity in Parkinson’s and other neurodegenerative diseases.
ISM8969, developed with Insilico’s proprietary AI platform Pharma.AI, is a brain-penetrant molecule designed to block NLRP3. By preventing activation of this inflammatory response in the brain, ISM8969 is expected to help reduce further neurodegeneration.
Pharma.AI is a generative tool, meaning it can integrate training data to produce new results, such as the molecular design of a therapeutic candidate. “We hope that AI could be the game-changer in the strive for novel and effective solutions,” Ren said.
Comprehensive preclinical studies showed that ISM8969 has potent activity and favorable safety and pharmacological profiles.
Mouse studies showed that animals with Parkinson’s-like disease had significantly poorer motor skills than healthy mice, but ISM8969 improved their performance. This occurred in a dose-dependent manner, meaning that higher doses led to greater motor improvement, with treated mice nearly reaching performance levels of healthy animals at certain dosages.
“Targeting age-related diseases including PD is a powerful approach to extending healthy longevity, and we hope Insilico can lead the way in breaking new ground and driving meaningful progress,” Zhavoronkov said.
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