| Mechanism class | Compound (Trial) | Sponsor | Phase | N | Population | Dose | Duration | Primary endpoint | Status | NCT | Ref |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Calcium channel blocker | Isradipine (STEADY-PD III) | NINDS/PSG/MJFF | III | 336 | >30 years, diagnosis <3 years, no DA rx | 5 mg twice daily vs placebo | 36 months | ΔUPDRS I-III at month 36 | Negative, no benefit on secondary outcomes | NCT02168842 | [17] |
| Urate elevation/antioxidant | Inosine (SURE-PD3) | NINDS/PSG/MJFF | III | 298 | >30 years, diagnosis <3 years, PD DaTscan, no DA rx (stable MAOB-I allowed), serum urate ≤5.7 mg/dL | Up to 3 g/day, titrated to serum urate level 7.1–8.0 mg/dL | 24 months | ΔMDS-UPDRS I-III at month 24 | Negative, early termination | NCT02642393 | [18] |
| Statin/anti-inflammation | Simvastatin (PD STAT) | University Hospital Plymouth NHS Trust | II | 235 | 40–90 years, H&Y ≤ 3, on DA rx with wearing off | 40 mg daily for 1 month, then 80 mg | 24 months with 2 month washout | ΔMDS-UPDRS III (OFF state) at month 24 | Negative | NCT02787590 | [19] |
| Iron chelation | Deferiprone (SKY) | ApoPharma | II | 140 | 18–80 years, diagnosis <3 years, stable dose of DA rx | 300, 600, 900, or 1200 mg twice daily vs placebo | 9 months | ΔMDS-UPDRS I-III at month 9 | Study completed 9/2019, results pending | NCT02728843 | |
| Deferiprone (FAIRPARKII) | ApoPharma | II | 372 | <80 years, disease duration <18 months, no DA rx | 15 mg/kg twice daily vs placebo | 36 weeks | ΔMDS-UPDRS I-III at week 36 | Active, not recruiting; estimated completion 4/2021 | NCT02655315 | ||
| Glucagon-like peptide 1 agonist | Exenatide | University College, London | II | 60 | 25–75 years, on DA rx with wearing off phenomena | 2 mg sc once weekly vs placebo | 48 weeks | ΔMDS-UPDRS III (OFF state) at week 60 | Positive; ΔMDS-UPDRS III + 1.0 (exenatide) vs −2.1 (placebo) (p = 0.0318) | NCT01971242 | [20] |
| Exenatide (Exenatide-PD3) ISRCTN14552789 (Vijiaratnam, 2021 #2793) ongoing | University College, London | III | 200 | 25–80 years, on DA rx for >4 weeks | 2 mg sc weekly vs placebo | 96 weeks | ΔMDS-UPDRS I-III (OFF state) at week 96 | Recruiting; estimated completion 9/2023 | NCT04232969 | ||
| Exenatide | Center for Neurology, Stockholm | II | 60 | 25–80 years, H&Y ≤ 2 (ON), on levodopa | 2 mg sc weekly vs placebo | 18 months | FDG-PET network analysis | Recruiting, estimated completion 10/2022 | NCT04305002 | ||
| SR-Exenatide (PT320) (sustained release) | Peptron, Inc. | II | 99 | 40–75 years, diagnosis <24 months, stable dose of levodopa | 2 mg sc weekly vs 2.5 mg sc every 2 weeks vs placebo | 48 weeks | ΔMDS-UPDRS III at week 48 | Recruiting, estimated completion 12/2021 | NCT04269642 | ||
| Liraglutide | Cedars-Sinai Medical Center | II | 57 | 25–85 years, diagnosis >2 years, DA-responsive | 1.8 mg sc daily vs placebo | 54 weeks | ΔMDS-UPDRS III at weeks 28 and 54 | Recruiting, estimated completion 12/2021 | NCT02953665 | ||
| c-Abl tyrosine kinase inhibitor | Nilotinib (NILO-PD) | Northwestern University/PSG/MJFF | II | 76 | 40–79 years, diagnosis >5 years, stable DA rx | 150 mg or 300 mg once daily vs placebo | 6 months | Safety and tolerability | Safe and well-tolerated; low CSF exposure with no change in dopamine metabolites | NCT03205488 | [21] |
| Nilotinib (PD Nilotinib) | Georgetown University | II | 75 | 40–90 years, H&Y 2.5–3, stable DA rx | 150 mg or 300 mg once daily vs placebo | 12 months | Safety and tolerability | Reasonably safe, increased CSF levels of DA metabolites | NCT02954978 | [22] | |
| K0706 (PROSEEK) | Sun Pharma | II | 504 | >50 years, symptoms <3 years, PD DaTscan, no DA rx | Low dose vs high dose once daily vs placebo | 40 weeks | ΔMDS-UPDRS II-III at week 40 | Recruiting, estimated completion 3/2023 | NCT03655236 | ||
| c-Abl kinase inhibitors in development for PD: IkT-148009 (Inhibikase): vodobatinib (Ph2, SPARC), Radotinib HCl (Ph2, Il-yang), and FB-101 (Ph1, 1ST Bio); | |||||||||||
| GBA | Ambroxol | University College, London | II | 23 | 40–80 years, H&Y 1–3, 1:1 with and without GBA1 mutations | Escalating dose to 1260 mg daily | 186 days | GCase, ambroxol levels in blood, CSF | Positive; decrease in GCase activity by 19% (p = 0.04), increased CSF ambroxol | NCT02941822 | [23] |
| Ambroxol | Lawson Health Research Institute | II | 75 | >50 years, mild to moderate dementia, H&Y 2–3.5 | 1050 mg daily vs placebo | 52 weeks | ΔADAS-cog, ADCS-CGIC at weeks 26 and 52 | Recruiting, estimated completion 12/2021 | NCT02914366 | ||
| GZ/SAR402671 (MOVES-PD) | Sanofi/Genzyme | II | 270 | 18–80 years, H&Y ≤ 2, PD-associated GBA1 mutation, stable DA rx | Part 1: increasing dose once daily; part 2: determined in part 1 | Part 1: up to 48–66 weeks; part 2: 52-week rx, followed by 104 weeks | Part 1: safety and tolerability; part 2: ΔMDS-UPDRS II-III at week 8 and 52 | Active, not recruiting; estimated completion 2/2024 | NCT02906020 | ||
Pittsburgh University
Greenamyre Lab
- Questions
Tim Greenamyre, MD, PhD
Love Family Professor & Vice-Chair of Neurology
Chief, Movement Disorders Division
Director, Pittsburgh Institute for Neurodegenerative Diseases
E-MAIL
INTERESTS
Currently, treatments for neurodegenerative diseases are inadequate; they typically address symptoms rather than the underlying degenerative process. As a result, we have no way to alter the inexorable progression of these devastating illnesses. My Lab is interested in defining mechanisms of neurodegeneration in order to identify new targets for development of neuroprotective (‘disease-modifying’) therapeutic strategies. Most of our current work is on Parkinson’s disease (PD), and we are particularly interested in mitochondrial abnormalities and their roles in causing oxidative damage, protein aggregation and neurodegeneration.
About 90% of PD cases do not have a clear genetic cause and are therefore called ‘sporadic’ or ‘idiopathic’ cases. However, a large number of genetic mutations have been identified which can result in relatively rare inherited forms of the disease – and there are still other mutations which may not cause the disease, but greatly increase the risk of developing PD. Identification of such mutations has provided crucial clues about potential mechanisms that we are currently pursuing. We are particularly interested in the biological interactions between environmental exposures and genetic factors that increase disease risk.
Among other approaches, we are examining the potential benefits of ‘gene therapy’ approaches. Autosomal dominant mutations are generally thought to produce a detrimental ‘gain-of-function’ for the affected protein, so the general approach is to reduce expression of those harmful proteins. On the other hand, autosomal recessive mutations are associated with a loss of function, so in this instance, we attempt to increase expression of the wildtype (normal) protein.
We are also working to develop ‘biomarkers’ of PD, using blood samples, that will help us determine whether neuroprotective, disease-modifying therapies are doing what they are designed to do.
- Susceptible PD population?
- Mitochondrial DNA damage: molecular marker of vulnerable nigral neurons in Parkinson’s disease,
- SN-specific 인데 어떻게 blood에서 상관?
- Change over time?
- 다른 mito dysfunction과의 관계? Ie is this the best mt marker?
- Is it age-dependent in normal people?
| Interested area | Not interested area |
|---|---|
| Genetic-environmental (toxin) interaction | Genetics itself (PRS) |
| Blood cell based PD early diagnosis using mt DNA damage |
Burton Lab
Edward A. Burton, MD, DPhil, FRCP
Berman Lab
Sarah B. Berman, MD, PhD
Dr. Berman’s research focuses on the role of mitochondria in neurodegenerative diseases, particularly Parkinson’s disease, and her laboratory is evaluating the role of mitochondrial dynamics in neurodegenerative diseases. Mitochondria, the energy-producing organelles in cells, are very dynamic in neurons, undergoing frequent division (fission) and fusion, and being transported in a regulated fashion. These processes are critical for synapse function and formation, programmed cell death mechanisms, and protection of mitochondrial DNA. Changes in mitochondrial dynamics are increasingly being linked to neurodegenerative diseases. However, these mitochondrial processes have been very difficult to study directly, particularly in the brain. Using novel methodology, Dr. Berman’s laboratory directly studies the role
Uncertain Spans
- 표 좌측 일부 셀 (“c-Abl kinase inhibitors in development for PD” 행)이 단일 통합 행인지 일반 행에 끼어든 메모형 줄인지 사진만으로는 단정 어렵다. 본 전사에서는 colspan=12로 통합 처리했다.
- 페이지 하단 Berman Lab 단락 마지막 문장은 사진 하단에서 “studies the role”에서 잘려 있어 다음 줄부터는 다음 사진으로 이어진다.
- “Greenamyre Lab Questions” 아래 첫 줄 “Mitochondrial DNA damage: molecular marker of vulnerable nigral neurons in Parkinson’s disease,” 다음 두 글자 정도가 사진 우측 어두운 영역으로 잘렸을 가능성이 있어 마침표/물음표 여부를 확정하지 않았다.