TABLE 2

Potential disease-modifying therapies with active clinical research

Adapted from Dawson and Dawson (2019) and McFarthing et al. (2020).

Mechanism	Name of Therapeutic	Sponsor	Phase	End Date: Expected or Actual	Recruitment Status	Clinicaltrials.gov ID Number	Resultsa
LRRK2 inhibitors	Denali-151	Denali Therapeutics	1b	Dec 2020	Active, not recruiting	NCT04056689	Ongoing
	Denali-201	Denali Therapeutics	1b	Dec 2019	Completed	NCT03710707	Promising PR-1b
	FB-101/1ST-102	1ST Biotherapeutics	I	Jun 2020	Recruiting	NCT04165837	Ongoing
Glucocerebrosidase: chemical chaperone to translocate mutant enzyme from the ER into lysosomes	Ambroxol	University College, London	II	May 2018	Completed	NCT02941822	Promising (Mullin et al., 2020)
	Ambroxol	Lawson Health Research Institute	II	Dec 2021	Recruiting	NCT02914366	Ongoing
	LTI-291	Allergen/Lysosomal Therapeutics	I	Oct 2018, Jun 2018	Completed	NL7061, NL6574	Promising PR-2c
GBA gene therapy: copy of GBA1 gene delivered by AAV9	PR001A	Prevail Therapeutics	II	Jun 20207	Recruiting	NCT04127578	Ongoing
Glucocerebrosidase: block accumulation of the glucocerebrosidase substrate, glucosylceramide	Venglustat (GZ/SAR402671)	Genzyme, a Sanofi company	II	Feb 2024	Active, not recruiting	NCT02906020	Not effective
α-Synuclein monoclonal antibodies to lower α-synuclein concentrations and block cell-to-cell transmission	Cinpanemab/BIIB054	Biogen	II	Jun 2021	Active, not recruiting	NCT03318523	Not effective
	Cinpanemab/BIIB054	Biogen	I	Jul 2021	Active, not recruiting	NCT03716570	Not effective
	Prasinezumab	Hoffman-La Roche; Prothena Biosciences Limited	II	Apr 2026	Active, not recruiting	NCT03100149	Ongoing
	MEDI1341	AstraZeneca	I	May 2022	Recruiting	NCT04449484	Ongoing
	MEDI1341	AstraZeneca	I	Apr 2021	Recruiting	NCT03272165	Ongoing
	Lundbeck-Lu-AF-82422	H. Lundbeck A/S	I	Dec 2020	Recruiting	NCT03611569	Ongoing
	UB-312	United Neuroscience, Ltd., Centre for Human Drug Research, Netherlands, Worldwide Clinical Trials	I	Jun 2022	Active, not recruiting	NCT04075318	Ongoing
	PD01a	Affiris AG	I	May 2014	Completed	NCT01568099	Promising (Volc et al., 2020)
α-Synuclein inhibitors of pathologic α-synuclein aggregation	ENT-01	Enterin	IIb	Dec 2021	Recruiting	NCT04483479	Ongoing
	PBT434	Alterity Therapeutic	I		Completed	U1111-1211-0052	Promising abstract (Stamler et al., 2019)
	UCB 0599 (formerly NPT200-11)	UCB Pharma	II	Oct 2023	Not yet recruiting	NCT04658186	Ongoing
	Anle138b	MODAG GmbH	I	June 2021	Not yet recruiting	NCT04685265	Ongoing
c-Abl kinase inhibition	SPARC-K0706	Sun Pharma	I	May 2019	Completed	NCT02970019	Promising abstract (Goldfine et al., 2019)
	SPARC-K0706	Sun Pharma	II	Mar 2023	Recruiting	NCT03655236	Ongoing
	Novartis: nilotinib	Georgetown	II	Jul 2020	Active, not recruiting	NCT02954978	Promising (Pagan et al., 2020)
	Novartis: nilotinib	Northwestern University	II	Sept 2019	Completed	NCT03205488	Not effective (Simuni et al., 2021)
	1ST Biotherapeutics, Inc.: FB-101	1ST Biotherapeutics, Inc.	I	Jun 2020	Recruiting	NCT04165837	Ongoing
GLP1 receptor agonist, decreases inflammation	Amylin Pharmaceutical/AstraZeneca: exenatide	University College, London	III	Sept 2023	Recruiting	NCT04232969/ ISRCTN14552789	Ongoing
	Exenatide	Center for Neurology, Stockholm	II	Oct 2022	Recruiting	NCT04305002	Ongoing
	SR-Exenatide	Peptron, Inc.	II	Dec 2021	Recruiting	NCT04269642	Ongoing
	Exenatide	University of Florida	I	May 2021	Active, not Recruiting	NCT03456687	Ongoing
	Novo Nordisk: liraglutide	Cedars-Sinai Medical Center	II	Dec 2021	Active, not recruiting	NCT02953665	Ongoing
	Sanofi: lixisenatide	University Hospital, Toulouse	II	Dec 2021	Active, Not recruiting	NCT03439943	Ongoing
	Neuraly: NLY01/1ST Biotherapeutics 103	Neuraly, Inc.	II	Aug 2022	Recruiting	NCT04154072	Ongoing
	Semaglutide		II	Dec 2024	Not yet recruiting	NCT03659682	Ongoing
Antioxidants	Deferiprone	Imperial College London	II	Dec 2014	Completed	NCT01539837	Promising (Martin-Bastida et al., 2017)
	Deferiprone	ApoPharma	II	Sept 2019	Completed	NCT02728843	Unknown
	Deferiprone	University Hospital, Lille	III	Oct 2011	Completed	NCT00943748	Promising (Grolez et al., 2015)
	Deferiprone	University Hospital, Lille	II	Apr 2021	Active, not recruiting	NCT02655315	Ongoing
	Hydrogen	Stone Brook University	II/III	July 2022	Recruiting	NCT03971617	Ongoing
Botanicals	DA-9805	Dong-A ST Co., Ltd.	II	Apr 2019	Completed	NCT03189563	Unknown
	WIN-1001X	Medi Help Line	II	Dec 2020	Recruiting	NCT04220762	Ongoing
	Lingzhi	Xuanwu Hospital, Beijing	III	Dec 2020	Recruiting	NCT03594656	Ongoing
Cell therapy	IPS-NSC cells	Allife Medical Science and Technology Co., Ltd	I	Feb 2021	Not yet recruiting	NCT03815071	Ongoing
Energy and mitochondria	UDCA	Sheffield Teaching Hospitals NHS Foundation Trust	II	Nov 2020	Active, not recruiting	NCT03840005	Ongoing
	EPI-589	PTC Therapeutics	II	Apr 2019	Completed	NCT02462603	Unknown
	CNM_Au8	Clene Nanomedicine	II	July 2021	Recruiting	NCT03815916	Ongoing
Microbiome/GIT	Rifaximin	University of California, San Francisco	I/II	Jun 2021	Recruiting	NCT03575195	Ongoing
	Rifaximin	Taipei Medical University Shuang Ho Hospital	I/II	Dec 2020	Recruiting	NCT03958708	Ongoing
	Fecal microbial transplant	Soroka University Medical Center	II/III	Jun 2020	Completed	NCT03876327	Unknown
	Fecal microbial transplant	University of Texas Health Science Center, Houston	I	Dec 2020	Recruiting	NCT03671785	Ongoing
	Resistant maltodextrin	Northwestern University	II	Jun 2021	Recruiting	NCT03667404	Ongoing
Neurotrophic factor	AAV2-GDNF	NINDS	I	Feb 2022	Active, not recruiting	NCT01621581	Ongoing
	AAV2-GDNF	Brain Neurotherapy, Inc.	I	Jun 2026	Recruiting	NCT04167540	Ongoing
	Cerebral dopamine neurotrophic factor	Herantis Pharma Plc.	I/II	Dec 2019	Completed	NCT03295786	Unknown
Targeting α-synuclein	Anle138b	MODAG GmbH	I	Jun 2021	Not yet recruiting	NCT04685265	Ongoing
	Mannitol	Hadassah Medical Organization	II	Dec 2020	Recruiting	NCT03823638	Ongoing
	Memantine	Wayne State University	III	Jul 2023	Recruiting	NCT03858270	Ongoing
LRRK2 ASO	BIIB094	Biogen; Ionis Pharmaceuticals	I	Dec 2022	Recruiting	NCT03976349	Ongoing
Inhibits ferroptosis	Cu(II)ATSM	Collaborative Medicinal Development Pty Limited	I	Feb 2020	Completed	NCT03204929	Promising abstract (Evans et al.)
	Young plasma infusions	Stanford University	I	Dec 2019	Completed	NCT02968433	Promising (Parker et al., 2020)
	Young plasma infusions	The Neurology Center	IV	Aug 2019	Completed	NCT04202757	Unknown
	Sargramostim	University of Nebraska	I	Dec 2022	Recruiting	NCT03790670	Ongoing
	Terazosin	Jordan Schultz, University of Iowa	I/II	Aug 2020	Enrolling by invitation	NCT03905811	Ongoing
	Terazosin	Cedars-Sinai Medical Center	II	Mar 2023	Recruiting	NCT04386317	Ongoing
	GRF6021	Alkahest, Inc.	II	Jul 2020	Completed	NCT03713957	Promising abstract (Rawner et al.)
Electron chain transporter	Idebenone	Second Affiliated Hospital, SOM, Zhejiang Univ	II/III	Jan 2023	Recruiting	NCT04152655	Ongoing
Mitochondrial support	Metabolic cofactor supplementation	Istanbul Medipol Univiversity Hospital	II	Sept 2020	Recruiting	NCT04044131	Ongoing
Mitochondrial support	Simvastatin	University Hospital Plymouth NHS Trust	II	Aug 2020	Active, not recruiting	NCT02787590	Ongoing

^aOngoing studies are those that are recruiting or active; promising studies are those that will be or should be moving to the next phase of testing based on either a press release, abstract, or published journal article.
^bPR-1: https://www.globenewswire.com/news-release/2020/08/06/2074205/0/en/Denali-Therapeutics-Announces-Decision-to-Advance-DNL151-into-Late-Stage-Clinical-Studies-in-Parkinson-s-Patients.html. Based on press releases and subsequent decisions by the company to move forward.
^cPR-2: https://parkinsonsnewstoday.com/2020/10/06/bial-acquires-parkinsons-treatment-lti-291-opens-us-research-center/. Press release saying Bial pharma has purchased drug and plans to move it forward. Recent press releases indicate this approach was determined to be not effective: https://www.michaeljfox.org/news/news-context-two-study-outcomes-disappoint-parkinsons-pipeline-remains-strong.
GIT, gastrointestinal tract; ASO, antisense oligonucleotide; NSC, neuronal stem cell; PR, press release; UDCA, Ursodeoxycholic acid.