Mission Therapeutics has dosed the first patient in its Phase Ib proof-of-mechanism study of MTX325 in patients with Parkinson’s disease (PD). 

MTX325 is a first-in-class, highly potent and selective, orally bioavailable and brain-penetrant inhibitor of the deubiquitinating enzyme (DUB) USP30.  

It has been designed to improve the clearance of dysfunctional mitochondria, support cell health and reduce inflammation – thus slowing or stopping processes thought to underpin the progression of PD.  

In preclinical studies, MTX325 demonstrated impact across multiple aspects of PD, including an increase in mitophagy, and beneficial effects on alpha-synuclein accumulation and nigrostriatal dopaminergic neurons.  

In a completed Phase Ia SAD/MAD study in healthy volunteers, MTX325 demonstrated high CNS penetration, while a PET study confirmed distribution into brain parenchyma. 

Dr Sarah Fritchley, Chief Development Officer of Mission Therapeutics, said: “Dosing the first Parkinson’s disease patient is a significant milestone in the development of MTX325, a potential disease-modifying treatment for this serious neurodegenerative disease, which affects almost one million people in the US and 1.2 million in Europe.” 

The MTX325-101 Phase Ib study is designed to establish clinical proof-of-mechanism and assess biological and pathophysiological responses using a wide range of biomarkers and imaging measures. Recruitment is ongoing, with 36 participants with mild to moderate idiopathic PD expected to enrol across the UK, Europe and Australia. A data readout is anticipated in late 2027. 

Dr Suhail Nurbhai, Chief Medical Officer of Mission Therapeutics, added: “By improving mitochondrial quality control, MTX325 has the potential to change the course of treatment for patients with Parkinson’s disease – moving beyond management of symptoms offered by current therapies. The start of the Phase Ib study is a major step forward on our journey to making this a reality.”