These compounds have all been studied in experimental models of MSA in the laboratory. The MSA Coalition provided the seed funding to allow researchers to carry out this critically important work. Before a compound can be approved by the FDA, this early laboratory work is required in order to build up enough evidence to propose a solid rationale for their use as a therapy for MSA patients.
Formal clinical trials using these compounds will need to be further developed for MSA patients. The MSA Coalition has funded the below early stage laboratory work – also known as “translational research” – which has served to lay the groundwork that may yet hold promise for the future.
The MSA Coalition is tremendously grateful to our community who have donated or raised critically needed funds that were directed towards these studies!
**NEW** September 29, 2021: Florey Institute of Neuroscience and Mental Health publishes research funded by The Multiple System Atrophy Coalition
April 2020: Nilotinib Fails to Prevent Synucleinopathy and Cell Loss in a Mouse Model of Multiple System Atrophy.
December 2019: Nilotinib Study Results Show People with Parkinson’s Disease Should Pass on This Drug
November 2019: FTY720-Mitoxy reduces synucleinopathy and neuroinflammation, restores behavior and mitochondria function, and increases GDNF expression in Multiple System Atrophy mouse models. (Fingolimod)
November2019: Researchers begin trial of drug to slow progression of neurodegenerative condition Multiple System Atrophy (Exendin-4)
Click on each compound to learn more details about the role of the MSA Coalition in funding these laboratory studies and what we have learned so far.
EXENDIN-4(EXENATIDE) - Phase 2 Clinical Trial in Progress *
** Preclinical work funded by the MSA Coalition **
Laboratory work to test Exendin-4 in MSA experimental mouse models was previously carried out at Bordeaux University, France. This project was funded by the MSA Coalition in 2015-2016 and showed positive results, paving the way for MSA patient trials.
Exendin-4 (Exenatide) is an FDA approved drug for treating Diabetes.
A Phase 2 pilot study to test Exendin-4 in MSA patients is beginning soon at the University College London.
https://clinicaltrials.gov/ct2/show/NCT04431713
Related Articles:
November 2019: Researchers begin trial of drug to slow progression of neurodegenerative condition Multiple System Atrophy
May 2017: New hope for devastating neurodegenerative disease
May 2017: Insulin resistance and exendin-4 treatment for multiple system atrophy
March 2017: Report on MSA Coalition funded research Exendin-4
June 2016: Glucagon-like peptide 1 analogues for treating multiple system atrophy: A translational study
NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.
CLR-01
** Preclinical work funded by the MSA Coalition **
Known as “molecular tweezers”, CLR-01 is being tested in MSA experimental mouse models through a joint collaborative project between University of California Los Angeles and Innsbruck Medical University.
This project was funded by the MSA Coalition in 2015-2017.
Related Presentations:
January 2019: Promising results in a new proof-of-concept preclinical study of the drug candidate CLR01
Related Articles:
March 2017: Targeting Alpha-Synuclein Pathology with the Molecular Tweezer CLR01 in Multiple System Atrophy
NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.
FINGOLIMOD
** Preclinical work funded by the MSA Coalition **
An FDA approved drug for treating Multiple Sclerosis is being tested in MSA experimental mouse models at Texas Tech University Health Sciences Center.
This project was funded by the MSA Coalition in 2016.
Dr. Ruth Perez presented preliminary results of this work at the MSA Coalition’s annual conference in 2016.
(Video link coming soon)
Related Articles:
NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.
LENALIDOMIDE
** Preclinical work funded by the MSA Coalition **
The anti-inflammatory drug Lenalidomide is being tested in MSA experimental mouse models at the University of California San Diego.
This project was funded by the MSA Coalition in 2015-2016.
Dr. Eliezer Masliah presented preliminary results of this work at the MSA Coalition’s annual conference in 2015.
(Video link coming soon)
Related Articles:
January 2017: Combination of alpha-synuclein immunotherapy with anti-inflammatory treatment in a transgenic mouse model of multiple system atrophy.
NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.
KALLIKREIN-6
** Preclinical work funded by the MSA Coalition **
Kallikrein-6 is being tested in MSA experimental mouse models at the University of California San Diego.
This project was funded by the MSA Coalition in 2013-2014.
Dr. Eliezer Masliah presented preliminary results of this work at the MSA Coalition’s annual conference in 2015.
(Video link coming soon)
Related Articles:
September 2015: A brain-targeted, modified neurosin (kallikrein-6) reduces α-synuclein accumulation in a mouse model of multiple system atrophy.
NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.
NILOTINIB
** Preclinical work funded by the MSA Coalition **
An FDA approved chemotherapy drug, Nilotinib was recently explored in a Phase 2A trial in Parkinson’s disease patients.
See results here: https://clinicaltrials.gov/ct2/show/results/NCT03205488
In 2016-2017, the MSA Coalition funded a pre-clinical study to assess this drug in MSA experimental animal models.
Results of this study were presented at the Movement Disorder Society Congress in 2018 and showed that Nilotinib failed to demonstrate positive effects in the experimental MSA mouse models. See the abstract here: Nilotinib for treating MSA: A preclinical proof of concept study
Related Articles:
April 2020: Nilotinib Fails to Prevent Synucleinopathy and Cell Loss in a Mouse Model of Multiple System Atrophy.
December 2019: Nilotinib Study Results Show People with Parkinson’s Disease Should Pass on This Drug
October 2018: Nilotinib for treating MSA: A preclinical proof of concept study
October 2018: A Phase 2A Study of Nilotinib in Patients with Advanced and Early Parkinson’s disease: Study Design
July 2016: Nilotinib Update: Where We Stand with a Cancer Drug for Parkinson’s
NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.
MPH (Ritalin)
** Preclinical work funded by the MSA Coalition **
This project was funded by the MSA Coalition in 2020. MSA Coalition Grant #2020-05-003 – $50,000
Project Title:
Testing MPH as a novel neuroprotective therapy in pre-clinical models of Multiple System Atrophy
Investigators:
Alessio DiFonzo (University of Milan, Italy) & Arianna Belluci (University of Brescia, Italy)
Project Summary:
The proposed study aims to verify whether methylphenidate (MPH) “Ritalin”, a drug used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, has a neuroprotective effect on patient-derived in vitro models of MSA. A-synuclein (asyn) is the pathogenic protein of MSA which aggregates and accumulates in glia and neurons, especially in oligodendrocytes and that constitutes the pathologic hallmark of MSA. We have recently found that Synapsin III (Syn III), a protein composing Lewy body insoluble fibrils of a-syn in the brain of Parkinson’s disease (PD) patients, can be also found within these glial cytoplasmic inclusions (GCI) in the postmortem brains of MSA patients (preliminary results). Our studies in the last few years have disclosed that Syn III controls a-syn aggregation as well as the related neurotoxcitiy and that MPH efficiently restores motor functions in a PD animal model by modulating the pathological a-syn/Syn III interplay in experimental models of PD. Our working hypothesis is that, since Syn III also composes GCI, MPH may also target these pathological aggregates in the brain of MSA patients and it can lead to the prevention or reduction of a-syn aggregation, resulting in neuroprotection. To test this hypothesis, we will generate and differentiate in vitro models of MSA and we will test if MPH rescue their phenotype.
Related Presentations:
Related Articles:
NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.
PLX5622
** Preclinical work funded by the MSA Coalition **
This project was funded by the MSA Coalition in 2020: MSA Coalition Grant #2020-05-005 – $50,000
Project Title:
Myeloid cell depletion as therapeutic target in multiple system atrophy
Investigators:
Juergen Winkler (University Hospital Erlangen, Germany) & Johannes Schlachetzki (University of California, San Diego, USA)
Project Summary:
Multiple system atrophy is a rare neurodegenerative disease with a rapid and devastating disease progression. At present, no therapy is available which stops or even slows disease progression of MSA patients. The immune response within the brain, so-called neuroinflammation, is an important feature of neurodegenerative diseases. In MSA patients, a severe immune response of microglia, the brain resident immune cells, has been described. Depletion of microglia showed beneficial effects in animal models of other neurodegenerative diseases such as Alzheimer’s disease or amyotrophic lateral sclerosis. In order to target the neuroinflammatory response in MSA, the main objective of this project is to reduce the number of microglia in a mouse model of MSA. Therapeutic effects will be investigated on a cellular and behavioral level. To reduce microglial numbers, we will use a compound (PLX5622) that has already been tested in a phase Ib clinical trial for treatment of rheumatoid arthritis. PLX5622 inhibits the colony-stimulating factor 1 receptor (CSF1R), which is expressed on microglia and plays a role in survival and maintenance of these cells. In case our preclinical study achieves a successful outcome, we aim to translate our results into a clinical trial in order to investigate its efficacy in MSA patients
Related Presentations:
Related Articles:
NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.
SYNUCLEAN-D
** NEW ** Preclinical work funded by the MSA Coalition **
Grant: “Optimization of a small molecule to inhibit a-synuclein aggregation in MSA”:
Awardees: Salvador Ventura, PhD & Wassilios Meissner, MD PhD
MSA Coalition Grant #2021-09-001 – $50,000
SynuClean-D, a small compound that inhibits alpha-synuclein aggregation, disrupts mature amyloid fibrils, prevents fibril propagation, and abolishes the degeneration of dopaminergic neurons in an animal model of Parkinson’s disease.
Related articles:
October 2018: New Compound Can Prevent Formation of Toxic Alpha-Synuclein Aggregates, Animal Study Finds
October 2018: Small molecule inhibits α-synuclein aggregation, disrupts amyloid fibrils, and prevents degeneration of dopaminergic neurons
September 2018: Molecule capable of halting and reverting neurodegeneration caused by Parkinson’s disease identified
Related Articles:
NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.
More MSA Treatment Pipeline Categories
CLINICAL TRIALS & STUDIES
EXPERIMENTAL LAB WORK
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