HYPE?
Media portrayal:
HOPE?
Scientific interpretation:

Diabetes drug (MSDC-0160) slows Parkinson’s progression in lab models

Original article: Mitochondrial pyruvate carrier regulates autophagy, inflammation and neurodegeneration in experimental models of Parkinson’s disease, Science Translational Medicine:  Dec 7, 2016

The takeaway

MSDC-0160, a drug originally developed to treat type 2 diabetes, has been shown to impede Parkinson’s disease progression in laboratory models of the disease. The study authors and drug developer are working through regulatory issues and seeking funding for human clinical trials.

Why is it important?

Current Parkinson’s treatments help manage symptoms but do not slow or stop disease progression. If MSDC-0160 is as successful in human clinical trials as it was in the lab, it could potentially give patients more years with reduced symptoms.

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IMPACT

  • Novelty 100%
  • Proximity 60%
  • Deliverability 100%

Impact opinion

The Cure Parkinson’s Trust (CPT) and Van Andel Research Institute (VARI) are currently working with MSDC to address regulatory issues and obtain funding to organize a clinical trial, which Brundin hopes can begin sometime in 2017.

Other things to know

  • MSDC-0160 is an investigational drug, meaning it is not currently approved for use to treat Parkinson’s
  • A clinical trial is in development but is not yet open.

The details

MSDC-0160 sensitizes cells to insulin allowing them to properly metabolize glucose, a process which is impaired in type 2 diabetes. MSDC-0160 appears to improve mitochondrial function by targeting the mitochondrial protein MPC (mitochondrial pyruvate carrier), which is a key controller of cellular metabolism. This keeps the cell and its trash removal systems working properly, protecting against the build up of abnormal proteins and eventual death of dopamine cells usually seen in Parkinson’s.

Next steps

The Cure Parkinson’s Trust (CPT) is also funding Dr Brundin in two addition ongoing preclinical research projects involving MSDC-0160:

  1. MSDC-0160 vs Pioglitozone (a similar drug previously tested in Parkinson’s) looking at target interaction
  2. MSDC-0160 plus Exenatide (another diabetes treatment which has shown potential disease modifying effects in Parkinson’s)

The goal of this ongoing work is to determine the level of interaction of MSDC-0160 with its target protein MPC and to understand if the combination of MSDC-0160 and Exenatide can change the course of the disease more potently than either drug alone. Positive results from this research would provide key supporting evidence to move MSDC-0160 into a clinical trial.

Related work

Another type 2 diabetes target (the GLP-1 receptor) has also been shown to be of relevance in Parkinson’s. Activation of GLP-1 receptors in the pancreas stimulates insulin release however GLP-1 receptors are also found throughout the brain and activation of such receptors has been shown to improve dopamine neuron function, reduce inflammation, switch on cell survival signals and help improve energy production in models of Parkinson’s.

A recent trial of Exenatide for Parkinson’s has shown promise in slowing the progression of Parkinson’s and two further trials using similar drugs, liraglutide and lixsenatide are being currently underway. More information about these trials can be found on the CPT website.

If you are interested in taking part in a clinical trial near you, take a look at Fox Trial Finder.

Original article: Ghosh A, Tyson T, George S, Hildebrandt EN, Steiner JA, Madja Z, Schultz E, Machiela E, McDonald WG, Escobar Galvis ME, Kordower JH, Van Raamsdonk JM, Colca JR, Brundin P. Dec 7, 2016. Mitochondrial pyruvate carrier regulates autophagy, inflammation and neurodegeneration in experimental models of Parkinson’s disease. Sci Transl Med 8(368):368ra174.
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