Table 3.

Description of repurposed FDA-approved drugs for Parkinson's disease of Huntington's disease.

			Clinical trials
Name	Target	Preclinical models (references)	CT identifier	Phase	First posted	Primary purpose	Population	Study design	Primary outcomes	Results
Ambroxol	Chaperone that stabilize the glucocerebrosidase (GCase) protein	PD mice and nonhuman primate models (Hutton et al., 2017)	NCT05287503	Phase 2	2022	Treatment	PD patients	60 participants	Change from baseline in Montreal Cognitive Assessment score. This 30-point test investigates global cognitive functions and it has been recommended for the assessment of Parkinson's dementia. The lower the score the worse the cognitive functions [Time frame: baseline and week 52]. Change from baseline in conversion rate from normal cognitive function (PD-N) to mild cognitive impairment (PD-MCI) and from PD-N or PD-MCI to Parkinson-Dementia (PD-D). Rate of conversion from normal cognitive status to MCI or from MCI to overt dementia over the 52-week treatment period [Time frame: baseline and week 52].	No study results posted
Isradipine	Calcium channel blocker	PD mice models (Hutton et al., 2017)	NCT00909545; NCT00753636; NCT02168842	Phase 2; Phase 2; Phase 3	2009; 2008; 2014	Treatment	PD patients	99 participants; 31 participants; 336 participants	Tolerability of the three dosages (5, 10, and 20 mg) of Isradipine CR. Tolerability will be judged by the proportion of subjects enrolled in a dosage group able to complete the 12 month study or to the time of initiation of dopaminergic therapy on their original assigned dosage. Tolerability of each active arm will be compared to placebo group [Time frame: Baseline to 12 months or the time to require dopaminergic therapy]; Tolerability of isradipine based on the number of participants that complete the study [Time frame: 1 year]; adjusted mean change in total unified Parkinson's disease rating scale (UPDRS) score. Efficacy of isradipine to slow progression of Parkinson's disease disability to be determined by the change in the total (Part I-III) UPDRS score in the active treatment arm vs. placebo between the baseline and 36 month visit. The change of UPDRS ranges from −30 to 80, larger value shows more disability from PD [Time frame: baseline to 36 months of treatment]. Adjusted mean change in adjusted UPDRS Score. Efficacy of isradipine to slow progression of Parkinson's disease disability to be determined by the change in the adjusted UPDRS Score in the active treatment arm vs. placebo between the baseline and 36 month visit. The change of adjusted UPDRS ranges from−100 to 150, larger value shows more disability from PD [Time frame: baseline to 36 months of treatment]	Safety, tolerability and efficacy as already been tested, but its properties as a disease modifying treatment for PD remain to be analyzed
Deferiprone	Iron chelator	PD rats models (Voulgaropoulou et al., 2019; Koponen et al., 2022)	NCT02655315	Phase 2	2016	Treatment	PD patients	372 participants	Global effect (symptomatic and disease modifying effects) on motor and non motor handicap. The change in the total movement disorders society-unified Parkinson disease rating scale score between baseline and 36 weeks (i.e. the end of the placebo-controlled phase for analysis of both disease-modifying and symptomatic effects) [Time frame: at 36 weeks]	No study results posted
Clenbuterol	B2AR agonist	PD mice models (Chen et al., 2019)
Salbutamol	B2AR agonist	PD rats models (Athauda and Foltynie, 2018)
Fenofibrate	Activation of peroxisome proliferator-activated receptor-β (PPAR-β)	HD mice models (Becker et al., 2008)	NCT03515213	Phase 2	2018	Treatment	HD patients	20 participants	Change in PGC-1alpha from baseline to month 6. Change in PGC-1alpha from baseline to month 6 [Time frame: baseline, 1, 2, 3, 4, 5, and 6 months]	No study results posted
KD3010	PPAR-δ agonist	HD mice models (Silveira et al., 2019)
Metformin	Activation of AMPK	HD mice models (Dexter et al., 2011; Martin-Bastida et al., 2017; Hider and Hoffbrand, 2018)	NCT04826692	Phase 3	2021	Treatment	HD patients	60 participants	Evaluate the effect of metformin on the scores obtained in different cognitive subtests that make up the unified Huntington's disease rating scale [Time frame: baseline—week 52]	No study results posted