Immunotherapy For Parkinson's:
Prophelactic vacine against toxic mis-folded alpha-synuclein.
This mechanism targets toxic (mis-folded, oligamer forms) alpha-synuclein on the move, outside the neuron cell walls by energizing the immune system and the generation of antibodies.
There are two forms of immunotherapy being tested for Parkinson's:
- Active immunization: inject a non-active fragment of the pathogen to trigger the immune system to generate resistance.
The immune effect tends to be longer lasting.
- Passive immunization: artificially generated antibodies.
The immune effect tends to be immediate.
Immunotherapies in trials:
- PD01A/PD03A: AFFITOPE PD01A: phase 2 trials 2014, 2020
Austrian vaccine against alpha-synuclein using Specific Active Immunotherapy (SAIT) to target rogue proteins.
Inject inactive alpha-synuclein to instigate the body to generate antibodies (as opposed to Biogen and Prothena approach to inject antibodies).
Seek to show a decline in alpha-synuclein levels in the blood.
Phase 1 trials (5 trial records 2014):
NCT01568099,
NCT01885494,
NCT02618941,
NCT02758730, and
NCT02216188.
phase 1 results
Corporation: AFFiRiS AG Vienna Biocenter in Vienna, Austria and Sympath Research Project
- PRX002/RG7935/RO7046015 (Prasinezumab): antibody therapy targeting alpha-synuclein.
Prasinezumab is designed to block the cell-to-cell transmission of the aggregated, pathogenic forms of alpha-synuclein.
Positive results were shown in halting Parkinson's progression and reduced motor function decline 35% after one year of treatment but they weren't good enough to meet the study's objective and is undergoing further development.
Information: Roche patient information
Trials conducted by Roche. Works well in transgenic mice: Reducing C-Terminal-Truncated Alpha-Synuclein by Immunotherapy Attenuates Neurodegeneration and Propagation in Parkinson's Disease-Like Models (2014: NIH and Prothena)
Reduced alpha-synuclein in the blood. Humanized IgG1 monoclonal antibody that targets aggregated C-terminally truncated form of alpha-synuclein that is considered neurotoxic, as well as alpha-synuclein propagation from cell to cell.
phase 2 trials (also known as the PASADENA study) NCT03100149 (2017-current)
phase 1b trials: NCT02157714 (2016)
Corporation: Prothena Dublin/San Francisco and Hoffmann-La Roche Switzerland
- Glycerol Phenylbutyrate: repurpose FDA approved drug to see if it can increase the removal of alpha-synuclein from the brain into the bloodstream.
phase 1 trials NCT02046434 2020
Institution: University of Colorado, Denver
- BIIB054 (Cinpanemab): info
human-derived monoclonal antibody passive vaccination targeting alpha-synuclein. Development discontinued Feb 2021
phase 2 trials NCT03318523 2018 SPARK study
phase 1 trials NCT02459886 2015
Corporation: Biogen (Note: Biogen acquired Neurimmune and former drug NI-202)
- LU AF82422: info
monoclonal IgG1 antibody targeting the C-terminal of alpha-synuclein.
phase 1 trials NCT03611569 2018
Corporation: H. Lundbeck A/S and Genmab A/S
- MEDI1341/TAK-341: info
high-affinity monoclonal antibody to monomeric and aggregated alpha-synuclein. The antibody intercepted cell-to-cell spreading of human alpha-synuclein fibrils in cell culture and in a mouse model of alpha-synuclein pathology propagation in brain.
phase 1 trials NCT04449484 2020
Corporation: AstraZeneca and Takeda Pharmaceutical Company
- PRX003: alpha-synuclein immunotherapy
phase 1 results
Research: Sympath Research Project
- UB-312: enhanced synthetic peptide-based alpha-synuclein immunotherapy
phase 1 trials NCT04075318 2020
Corporation: United Neuroscience
- ABBV-0805: info
humanized monoclonal antibody targeting alpha-synuclein. Antibodies (PD1601, PD1602) bind oligomeric/protofibrillar alpha-synuclein with nanomolar affinity and high selectivity over monomeric protein.
Pre-clinical mouse studies show reduced levels of alpha-synuclein oligomers and protofibrils in the central nervous system, less severe motor abnormalities and a doubling of the life-span after antibody treatment.
phase 1 trials NCT04127695 2019
Corporation: AbbVie (licensed from BioArctic AB)
Targeting alpha-synuclein:
There are fundamentally different approaches being taken in this domain:
- Target DNA/mRNA so the body reduces the amount of the alpha-synuclein protein generated by cells thus starving any attempts of aggregation
- Influence the clean-up of alpha-synuclein by neurons using autophagy or bind directly to alpha-synuclein to break-up Lewey bodies, fibrils and oligomers
- Small molecule drugs to prevent the formation of alpha-synuclein oligomers, fibrils and Lewey bodies
These drugs are targeting the mal-folded protein which damage or kill neurons and is considered to be the fundamental cause of the disease.
- Anle 138b: more info,
more info on phase 1 trial
Reduce intra-cellular oligomers and targeted specifically to processing toxic misfolded alpha-synuclein aggregations into smaller non-toxic variants of the protein to halt prion-like propagation, University of Cambridge
phase 1 trials NCT04208152 (2020) and NCT04685265 2021 (UK trials)
Corporation: MODAG GmbH (Germany)
- ATV: aSyn high affinity antibody
Corporation: Denali Therapeutics
- MEDI1341: info
phase 1 trials 2017
Corporation: AstraZeneca (Partnered with Takeda)
- NPT200–11:
Three prong approach for this small molecule drug:
- Inhibit aggregation of mis-folded proteins
- Inhibit brain inflammatory processes
- Rectify defects in the cellular mechanisms for clearing aggregates of mis-folded proteins
phase 1b trials NCT02606682 2016
Corporation: Neuropore
- Nilotinib: re-purpose of a blood cancer leukemia drug FDA approved in 2010 as a therapy for Lewy body clean-up by enhancing autophagic clearance of alpha-synuclein.
News release
phase 1 trials NCT02281474
phase 2 trials NCT02954978
Corporation: Novartis
- Radotinib/IY5511: re-purpose of a blood cancer leukemia drug FDA approved.
A c-Abl inhibitor which exhibits improved pharmacokinetic properties and BBB penetration compared to nilotinib and other c-Abl inhibitors, was tested in a preclinical alpha-synuclein preformed fibrils (PFF) model of sporadic PD.
Prevents dopamine neuron loss and behavioral deficits following alpha-synuclein PFFs-induced toxicity.
phase 2 trials NCT04691661 (2021)
Corporation: Il-Yang Pharm Co Ltd
- Nortriptyline: re-purpose of an FDA approved anti-depressant as a therapy to combat the aggregation of alpha-synuclein.
Nortriptyline does not clear toxic alpha-synuclein aggregates but interferes with the aggregation process and renders alpha-synuclein effectively more soluble and hence easier to clear within the cell.
Part of a larger study of antidepressants in the treatment of Parkinson's disease (ADepT-PD).
It is also hoped that it will help with depression and motor function.
News description
phase 3 trials NCT03652870 (2018)
Institution: University College, London
- PBT (Phenylbutyrate-triglyceride):
Glycerol Phenylbutyrate: flushes alpha-synuclein to blood stream.
trials NCT02046434
University of Colorado, Denver Curt R Freed, MD
- K0706 / SCC-138: an oral compound that acts as a suppressor of an enzyme called Abl tyrosine kinase which has been associated with oxidative stress and alpha-synuclein-induced neurodegeneration.
PROSEEK study.
phase 2 trials NCT03655236 2018
phase 1 trials NCT02970019
Corporation: Sun Pharma Advanced Research Company Limited (SPARC)
- ANVS-401:
alpha-synuclein aggregation inhibitor.
Also see pipeline
Corporation: Annovis Bios
- NPT088: Antibodies. NPT088 is their first GAIM candidate targeted for Alzheimer’s but also hopefully useful for Parkinson's. Completed phase 1B.
GAIM: General Amyloid Interaction Motif is a technological approach to break apart mis-folded protein aggregates.
Corporation: Proclara Biosciences
- UCB0599: Alpha-synuclein Oligomerization (a step in alpha-synuclein aggregation) Inhibitor.
phase 1b trials
Corporation: Neuropore teamed with UCB pharma and University of California San Diego
- ENT-01:
Squalamine based. Targets removal of alpha-synuclein in the gut and constipation.
phase 2 trials NCT03781791 2021 "KARMET" study
phase 2 trials NCT04483479 2021 "Roll-over" study
Corporation: Enterin
Neurotrophic Factors:
The goal of these drugs is to inhibit the progression and development of Parkinson's by restoring neurons and by inducing growth of new neurons by using neurotrophic factors.
Early work in this area inserted tubes in the brain to deliver GDNF neurotrophic factors directly to the putamen with positive results including a 39% improvement in off-medication motor function and a 64% reduction in dyskinesias (ref: Gill).
The effects were shown to be long lasting (3 yrs+) in a follow-up study (ref: Patel).
Current efforts include drug development with techniques to pass through the blood-brain-barrier including small molecule development and gene therapy.
GDNF is not the only neurotrophic factor as there is also neurturin, persephin, and artemin, all with positive/neuroprotective effects.
Each also has a respective receptor which when bound will activate another surface protein called Ret proto-oncogene (RET) to result in cell growth and survival.
Also see the association of exercise and Brain Derived Neurotrophic Factors (BDNF) to neuron health.
- GDNF based drugs: this class of drugs are based on Glial cell-derived neurotrophic factor (GDNF), a protein encoded in the GDNF gene which promotes the growth, survival and differentiation of both developing and mature dopaminergic neurons.
In mature neurons they promote neuronal survival, induce synaptic plasticity, and modulate the formation of long-term memories and even capable of regrowing damaged neurons in test tubes and animal models.
References:
GDNF Related trials:
- HGF based drugs: therapeutics specifically designed to enhance the activity of Hepatocyte Growth Factor (HGF) and its receptor, MET, which are expressed in normal central nervous system function, in order to impact neurodegeneration and regenerate brain tissue.
HGF Related trials:
- ATH-1017: a small molecule therapeutic to enhance the activity of HGF. Alzheimer's drug for the broader dementia population, including Parkinson’s disease dementia.
Phase 1 trial: NCT04488419
Corporation: Athira
- BT13: a smaller molecule, is able to cross the blood-brain barrier (unlike GDNF which is a large molecule and can not), and therefore could be more easily administered as a treatment.
BT13 binds the same signaling receptor as GDNF (RET receptor).
Primary research performed at the University of Helsinki. Patents held.
References:
- CDNF: Herantis: Cerebral Dopamine Neurotrophic Factor (CDNF): phase 2 gene therapy
Phase 2 trial: NCT03295786
Phase 2 trial extension: NCT03775538
Corporation: Herantis Pharma Finland
- NNI-362: (backup NNI-370) neurorestorative and shown to halt further dopaminergic connection loss in a pilot model of chronic, progressive Parkinson’s disease.
Demonstrated a trend toward regeneration of neuron connections in the caudate putamen and at the same time increased the number of new neuronal progenitors, suggesting neuron regeneration, not just neuroprotection.
Phase 1 trial: NCT04074837 Alzheimer's, Parkinson's trials not started.
Corporation: Neuronascent
Gene Therapy:
Gene Therapy attempts to treat Parkinson's by modifying DNA to correct genetic errors.
Gene therapy is also used as a delivery mechanism for drugs which can not pass the blood-brain-barrier.
This methodology uses a non-replicating virus which does not produce an immune response or illness (typically AAV: adeno-associated viruses) to carry the DNA instructions to manufacture a protein (the medication like a neutrophic factor) to a specific type of cell (dopamine neuron cells).
In this way the medication is manufactured at the delivery location as opposed to performing a complex brain surgery to deliver the medication to Parkinson's affected regions of the brain.
- CERE-120 (AAV-NTN): a gene therapy product designed to deliver the glial cell line-derived neurotrophic factor (GDNF) neurturin, for Parkinson's disease using the AAV2 virus and surgical injections targeting the putaminal region of the brain.
Pase 2 trial completed (fail).
Published paper: Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial (2010) Study results: fail
Phase 2 trial: NCT00400634
Corporation: Ceregene Inc
- AAV2-neurturin (NTN): gene delivery of the trophic factor neurturin via an adeno-associated type-2 vector (AAV2) virus.
Autopsies after 4 years revealed neuron branching and persistent neurturin neurotrophic factor production.
Study completed. Company is now in phase 2 trials of their new gene therapy drug candidate, CERE-120 (see above).
Phase 1 trial: NCT04167540
Corporation: Ceregene Inc
- AAV2-GDNF: glial cell line-derived neurotrophic factor (GDNF) gene therapy using the AAV gene therapy platform to slow or reversing Parkinson's disease progression.
Phase 1 trial: NCT04167540
Corporation: Brain Neurotherapy Bio, Inc and UCSF
- AAV2-GDNF: glial cell line-derived neurotrophic factor (GDNF) gene therapy using the AAV gene therapy platform to slow or reversing Parkinson's disease progression.
Phase 1 trial: NCT01621581
Institution: National Institute of Neurological Disorders and Stroke (NINDS) USA
- OXB-102: a virus that modifies neurons so that they produce dopamine.
Phase 2 trial: NCT01856439
Corporation: Oxford Biomedica
- ST-502: gene regulation therapy approach delivered with AAVs which is alpha-synuclein-targeted
development announcement: Yahoo finance announcement
Corporation: Sangamo and Biogen
Targeting Inflammation Response:
Drugs in this category are targeted at various inflammation pathways.
Inflammation is usually a by-product of immune system activation and is meant to have a duration long enough to process a pathogen or heal tissue.
When the inflammation becomes chronic it usually has harmful side-effects including cell death, specifically dopaminergic neurons in the substantia nigra in the case of Parkinson's disease.
GLP-1:
Several GLP-1R agonists are approved for treating Type 2 diabetes, in which they ease insulin resistance and normalize glucose metabolism.
In the brain, GLP-1R agonists improve glucose metabolism too, while also stimulating neurogenesis and neuron survival, and quelling inflammation.
Weight loss may be problematic for some.
For more see:
Drugs targeting Glucagon Like Peptide-1 (GLP-1): hormone which signals the body to produce insulin and blocks glucose release.
- NLY01: FDA approved for use in treating type 2 diabetes and shown to slow Parkinson's progression in transgenic mice. Neuroprotective and inhibits secretion of neuroinflammatory cytokines by microglial cells by targeting the GLP-1 signalling pathway.
NLY01 was shown to have a neuroprotective property by mediating the behavior of microglia (immune system macrophage cells in the brain which act as immune sentinels orchestrating an inflammatory response) and their effect on astrocytes (cells that bridge nutrients from capillaries to neurons).
Activation of microglia can cause them to release inflammatory agents which in turn cause astrocytes to shift to a dysfunctional reactive state which in turn leads to neuron cell death.
NLY01 prevents the microglia from being reactive and making the astrocytes dysfunctional.
thus NLY01 saves neurons.
Half-life of 88 hours in primates which is an improvement over its predecessor Exenatide which had a half life of 2.5 hours.
Weekly injection.
Also see:
Phase 2 trials: NCT04154072 Dosage: 2.5 mg or 5 mg weekly injection for 36 weeks
Trial study enrollment PRISM study - tweaked second round (no usage of levodopa medications allowed)
Corporation: Neuraly, Inc
- Exenatide (Byetta, Bydureon):
FDA approved (2005) for use in treating type 2 diabetes and obesity.
Not yet approved for Parkinson's but available as an "off-label" prescription.
Not insulin but a GLP-1 agonist which increases the amount of insulin the pancreas releases.
Targets the GLP-1 signalling pathway.
Side effects include nausea, loss of appetite and weight loss. Weight loss can be extreme. FDA black box warning: increased incidence in thyroid C-cell tumors in rats (> 2 x clinical dose in male rats and 27 x clinical dose in female rats).
Also see:
Phase 2 trials: NCT04305002 Dosage: Injections, 2 mg once weekly for 18 months
Institution: Center for Neurology, Stockholm Sweden
- Lixisenatide: re-purposed FDA approved type 2 diabetes drug. Has neuroprotective properties in animal models of PD.
Phase 2 trials: NCT03439943
Corporation: University Hospital, Toulouse (France)
- PT320: an ultrasonic spray drying technology that produces sustained release of Exenatide, an FDA approved drug to treat patients with Type 2 Diabetes and obesity.
Injection once every two weeks.
Phase 2a trials: NCT04269642
Corporation: Peptron Inc (South Korea)
- Liraglutide (Victoza, Saxenda): FDA approved (2010) for use in treating type 2 diabetes and obesity.
For use by patients with a high body mass index (BMI) greater than 30 kg/m2 (overweight). Targets the GLP-1 signalling pathway with a longer half-life than exenatide (once daily injection).
Side effects include thyroid cancer and pancreatitis.
Information: study description: "There is reason to believe that liraglutide may prove superior to exenatide in treating PD."
Phase 2 trials: NCT02953665
Corporation: Novo Nordisk
- Lixisenatide (Adlyxin): re-purposed FDA approved drug. Increases neurogenesis and decreased microglial activation.
Daily injections.
Phase 2 trials: NCT03439943
Institution: University Hospital, Toulouse
- Semaglutide: a weekly injectable dosage form branded as Ozempic by Novo Nordisk and approved by the FDA in 2017. An oral form of semaglutide, to be called Rybelsus, was approved by the FDA towards the end of 2019 and by the EMA in January 2020.
Phase 2 trials: NCT03659682
Institution: Oslo University Hospital
Nurr1:
For more see
details on Nurr1 and inflammation.
- prostaglandin A1 and E1: increases Nurr1 effectiveness leads to an increase in dopamine levels, which then results in the treatment of Parkinson's disease.
Nurr1 also limits inflammatory responses in the central nervous system and specifically protects dopaminergic neurons.
The hormone like compound prostaglandin A1 and E1 bind to and activated the Nurr1 protein to protect dopamine neurons against neurotoxins.
This research lead to the finding that three existing drugs (Chloroquine, Amodiaquine and Glafenine) activate Nurr1.
This has not lead to human clinical trials but is the subject of a funded study by the MJF Foundation.
Also see PGE1 and PGA1 bind to Nurr1 and activate its transcriptional function
CCR3:
CCR3 is expressed on multiple leukocytes (shite blood cells) important to the allergic inflammatory response.
- AKST4290-211: is a CCR3 inhibitor with two approach vectors, a broad anti-inflammatory mechanism and an immune modulatory mechanism through the body's innate immune cells.
Convenient small molecule pill taken twice a day.
Also see Alkahest: AKST4290: targeting Eotaxin
Phase 2 trials: NCT04369430
Corporation: Alkahest
NLRP3:
- MCC950: inhibits NLRP3 inflammasome generation and ASC speck formation to block inflammation.
Crosses the blood brain barrier to lower precursors of the inflammatory cytokines: IL-1b, Caspase-1, and ASC levels dramatically resulting in a marked reduction in the number of alpha synclein aggregates.
References:
Research Institution: University of Queensland Institute for Molecular Biosciences
Corporation: Inflazome
- NLR antagonists: developed as a treatment for a range of diseases where NLR inhibitors (not just NLRP3) can be helpful for a range of diseases (not just Parkinson's)
Corporation: IFMthera LLC (Bristol-Meyers Squibb)
- NT-0167: developed as a treatment for a range of diseases where NLRP3 over-activation has been implicated (not just Parkinson's)
Corporation: NodThera
- Inzomelid: developed by startup to commercialize NLRP3 inflammasome blocker
Phase 1 trials: NCT04015076 (2020)
Corporation: Inflazome UK Ltd
For more on NLRP3 see:
Other Inflammation Pathways:
- NPT520-34: Neuroinflammation - receptor 2 antagonist small molecule drug that reduces the astrocytic and microglial of markers of neuroinflammation and neuropathology.
Phase 1 trials: NCT03954600 completed 2019
Corporation: Neuropore
- NPT1220-312: Neuroinflammation & Autophagy: (TLR2 Antagonists) Toll-like receptor 2 (TLR2) antagonist that reduces markers of inflammation and neurotoxic protein burden including Parkinson’s disease patient-derived iPS neurons.
Pre-clinical
Corporation: Neuropore
- Protein kinase-C (PKC5) inhibitor: info PKC plays a critical role in a number of functions from cell growth to death. Inappropriate activation contributes to the development and progression of cell death and neurodegenerative disorders.
PKC5 offers a neuroprotective effect.
Corporation: PK Biosciences Corp
- 1R43NS110129-01: novel anti-neuroinflammatory agents for treating neurodegenerative disorders
Corporation: PK Biosciences Corp
- Sargramostim (Leukine): FDA approved (1991) for use in bone marrow transplantation treatment for immunomodulation and to stimulate the growth of white blood cells in your body.
Phase 1 trials: NCT03790670
Corporation: Partner Therapeutics, Inc
- Fasudil:
potent Rho-kinase inhibitor and vasodilator approved by the FDA to treat cerebral vasospasm and stroke, re-purposed to treat Parkinson's.
Fasudil is highly active under conditions of inflammation and injury, and target inhibition by fasudil enhances axonal growth, regeneration, and promotes neurological recovery following spinal cord injury, making fasudil a promising therapeutic drug for neurological diseases.
Research: Fasudil attenuates aggregation of α-synuclein in models of Parkinson’s disease (2016)
Trials: anouncement 2017
Institution: Michael J Fox Foundation
Targeting LRRK2:
These drugs are targeting patients with the gene LRRK2, identified as having a genetic link to Parkinson's.
- DNL151:
Phase 1b results published
Phase 1b trials: NCT04056689
Corporation: Denali Therapeutics
- DNL201:
Phase 1b trials: NCT03710707
Corporation: Denali Therapeutics
- BIIB094: antisense oligonucleotide (ASO) designed to bind to LRRK2 mRNA and mediate its degradation, reducing LRRK2 protein levels. Antisense oligonucleotide that targets the RNA that makes LRRK2
Phase 1 trials: NCT03976349
Corporation: Biogen
Targeting GBA:
These drugs are targeting patients with the GBA gene mutation, identified as having a genetic link to Parkinson's.
- AiM-PD/Ambroxol:
phase 2 for Parkinson's. Existing re-purposed drugs NCT02941822
Ambroxol: breaks up phlegm, used in the treatment of respiratory diseases and indicated that it may reduce the build-up of alpha-synuclein in neurons for those with the single GBA gene mutation.
Ambroxol is believed to triggers exocytosis (cell waste removal rather than recycling) by lysosomes (ref).
Phase 2 trial: NCT02941822
Also see: The Ambroxol Trial - The facts
- S-181:
Attempts to reduce the build-up of alpha-synuclein in neurons for those with the GBA gene mutation.
Also see: A modulator of wild-type glucocerebrosidase improves pathogenic phenotypes in dopaminergic neuronal models of Parkinson's disease
- BIA28-6156/LTI-291:
Using pharmacological activation of the GCase enzyme to provide therapeutic benefits.
LTI-291 is designed to target the GCase enzyme to increase activity and improve glycosphingolipid metabolism in the lysosome.
Pre-clinical studies have shown that LTI-291 easily crosses the blood-brain-barrier and accesses the GCase enzyme within the brain and central nervous system.
Phase 1 trials.
Corporation: Bial bought Lysosomal Therapeutics
- GZ/SAR402671 (Venglustat): repurposed drug. Showed promise in treating Gaucher’s disease. Development halted Feb 2021.
Phase 2 trials: NCT02906020 (MOVES-PD study)
Corporation: Sanofi Genzyme
Targeting Mitochondria:
Mitochondria are the energy source and metabolism for cells and if impaired, it increases the risk of alpha-synuclein mis-folding and aggregation.
It has also been shown that alpha-synuclein mis-folding and aggregation impair mitochondria function.
These drugs hope to help mitochondria health, neuron cell energy and protein processing and thus decrease alpha-synuclein mis-folding and aggregation.
- Ursodiol/UDCA Ursodeoxycholic Acid (Actigall, Urso): re-purposed gallstone drug to address mitochondrial dysfunction in Parkinson's patients.
This drug aims to be neuroprotective. Also targeted for those with the PARK2/PARKIN and PARK8 gene mutations.
UDCA or Ursodeoxycholic Acid is a naturally occuring acid found in bile to help digest fats and dissolve gallstones.
UDCA has a restorative effect on mitochondria and found to protect dopamine cells grown in culture from apoptosis, or programmed cell death.
Research:
Phase 1 trial: NCT02967250
Institution: University of Minnesota: Clinical and Translational Science Institute
- EPI-589 (R-Troloxamide quinone): re-purposed drug to address mitochondrial dysfunction in Parkinson's patients.
Phase 2 trial: NCT02462603
Corporation: PTC Therapeutics
- 3R43NS108852-01S1 and 1R43NS108852-01: improve the efficiency of dysfunctional mitochondria in Parkinson's
Corporation: PK Biosciences Corp
- not registered: treatment to lower the levels of the mitochondrial protein Miro1 to help protect mitochondria.
Also see: Scientists find potential diagnostic tool, treatment for Parkinson’s disease
Corporation: AcureX Therapeutics
Therapy for Cognitive Decline with Parkinson's:
- ANAVEX2-73 (blarcamesine):
this drug is a protein and a Sigma-1 receptor agonist which serves as a molecular chaperone (assists with the folding of other proteins) and functional modulator involved in restoring homeostasis.
The Sigma-1 receptor is located in the endoplasmic reticulum (ER) mitochondria-associated membrane.
Sigma-1 acts as a chaperone to the IP3R protein and helps facilitate calcium flow from the ER under stress.
Increasing Sigma-1 lowers ER stress, promotes synaptic plasticity and increase neurotrophic factors.
When ER stress is high, misfolded proteins start to accumulate.
The drug ANAVEX2-73 is expected to be neuroprotective and restorative.
Study for Patients With Parkinson's Disease With Dementia.
Information: drug mechanics
phase 2 trials NCT04575259 2020 (Spain, Australia)
Corporation: Anavex Life Sciences Corp
- GRF6021: proprietary plasma-derived product, administered by intravenous (IV) infusion. Designed to replenish regenerative positive chronokines (circulating proteins that increase or decrease with age).
Phase 2 trials: NCT03713957 completed 2020
Corporation: Alkahest
- Ceftriaxone:
repurposed drug for the treatment of mild to moderate Parkinson's disease dementia (PDD).
Found to have functions in reducing glutamatergic hyperactivity and excitotoxicity and may exhibit neuro-protective functions as the mechanism in PDD treatment.
phase 2 trials NCT03413384
Institutions: Chung Shan Medical University Hospital, National Taiwan University Hospital,Taichung Veterans General Hospital, Kaohsiung Medical University Hospital and Tungs' Taichung MetroHarbor Hospital
- LY3154207:
potential treatment for Parkinson’s disease dementia (PDD) (Lewy Body Dementia) by enhancing dopamine receptor D1, a dopamine receptor involved in cognition.
phase 1 trials NCT02562768 2015
phase 2 trials NCT03305809 2017
Corporation: Eli Lilly and Company
- SAGE-718:
For Parkinson's patients with cognitive impairment.
phase 2 trials NCT04476017 2020
Corporation: Sage Therapeutics
Dopamine Therapy for Parkinson's Symptoms:
Drugs trying to improve on Levodopa and its variants by improving the side effects.
- CVN424: anticipated to induce positive therapeutic effects similar to current Levodopa treatments for Parkinson’s while avoiding side effects such as dyskinesia.
Selectively targets the dopamine D2 receptor-dependent, indirect pathway. Phase 2 trials
Corporation: Cerevance
- ND0612: Continuous Subcutaneous Infusion of Carbidopa and Levodopa
Phase 3 trial: NCT04006210
Corporation: Xenoscience
- Tavapadon: partial agonist used to balance signalling of neurons from the direct motor pathway (thalamus to the cortex D1/D5 receptors), and indirect motor pathways (D2/D3 receptors) to allow for proper motor control and avoid dyskinesias. Phase 3
Phase 3 trial: NCT04223193
Corporation: Cerevel
- P2B001: contains low doses of the dopamine agonists pramipexole, and the monoamine oxidase-B inhibitor rasagiline.
Phase 3 trial: NCT03329508
Corporation: Pharma Two B Ltd.
- JP-1730/Fipamezole: antagonist of an adrenergic receptor for the potential treatment for levodopa-induced dyskinesia
Trial: NCT01140841
Corporation: Bausch Health Americas, Inc.
Other Therapies:
- Isradipine:
approved by the FDA to treat high blood pressure. Isradipine may block the damage caused by the flow of certain chemicals through specialized channels that are present in the types of brain cells that are affected in PD patients.
phase 3 trials NCT02168842 2020
Institution: University of Rochester
- Deferiprone:
iron chelator approved by the FDA to treat iron overload, re-purposed to treat Parkinson's.
Addresses high iron and oxidative stress that have been implicated in the neurodegenerative process of Parkinson's.
phase 2 trials NCT01539837 2020
Institution: Imperial College London
- Nilotinib:
Tyrosine kinase inhibitor antineoplastic agent approved by the FDA to treat leukemia, re-purposed to treat Parkinson's. Found to increase alpha-synuclein clearance and improve motor function.
phase 2 trials NCT03205488 2020
Institution: Northwestern University
- Simvastatin:
Neuroprotective Treatment for Parkinson's Disease. FDA approved treatment for cholesterol and triglyceride levels, re-purposed to treat Parkinson's.
phase 2 trials NCT02787590 2020
Institution: University Hospital Plymouth NHS Trust
- Rucaparib: PARP inhibition
a protein called PARP-1 is a key mediator of cell death via Parthanatos, supporting the potential therapeutic benefits of PARP inhibitors for halting Parkinson’s progression.
Rucaparib is FDA approved as a treatment for ovarian cancer, re-purposed to treat Parkinson's.
Press release: Road to cell death more clearly identified for Parkinson's disease 2018
Institution: Johns Hopkins University School of Medicine
- Nilotinib:
FDA approved to treat leukemia, re-purposed to treat Parkinson's.
phase 2 trials NCT03205488 2020
Institution: Northwestern University
- Pridopidine:
this drug is a protein and a Sigma-1 receptor agonist being evaluated as a treatment for Levodopa-induced dyskinesias in Parkinson’s.
phase 2 trials NCT03922711 2020
Corporation: Prilenia
- ITI-214:
PDE-1 inhibitor
phase 2 trials NCT03257046 completed 2018
Corporation: Intra-Cellular Therapies Inc
- Terazosin:
Stimulates glycolysis via PGK-1
phase 2 trials NCT03905811 2018
Institution: University of Iowa
- KM819:
FAF-q inhibitor
phase 1 trials NCT03022799 completed 2018
Corporation: Kainos Medicine Inc
- Leukine (Sargramostim):
Recombinant GM-CSF. Potential motor control and mobility improvements.
phase 1 trials NCT01882010 completed 2016
Institution: University of Nebraska
- TD-9855 (Ampreloxetine):
For Parkinson's patients with symptomatic Neurogenic Orthostatic Hypotension (nOH) showing primary autonomic failures.
Treatment for those displaying symptoms of low blood pressure where one feals dizy of faint from standing up from a seated or prone position.
SEQUOIA study.
phase 3 trials NCT03750552 2020
Corporation: Theravance Biopharma
Clinical Trials:
One can participate or research trials at the following websites: