Protein That Increases Dopamine Release Could Become Parkinson’s Therapy, Study Reports

Protein That Increases Dopamine Release Could Become Parkinson’s Therapy, Study Reports

Administering a naturally occurring protein directly to the brains of rats increased the amount of the neurotransmitter dopamine going to the animals’ nerve cells, suggesting it could be a way to treat Parkinson’s, a study reports.

The findings further demonstrate the MANF protein’s potential to treat Parkinson’s and other neurodegenerative disorders, according to the company developing such a therapy, MANF Therapeutics. MANF Therapeutics, a subsidary of Amarantus Bioscience, is conducting preclinical-trial studies on the potential treatment that it hopes will lead to trials.

One of the hallmarks of Parkinson’s is the death of dopamine-producing brain cells. Dopamine facilitates  communication between nerve cells.

Another Parkinson’s hallmark is the clumping of abnormal forms of α-synuclein protein in nerve cells — which scientists call Lewy bodies.

Preventing these two events could be a way to treat the disease, researchers believe.

MANF proteins belong to a protein group called neurotrophic factors. They help maintain nerve cells’ health and function and promote their recovery from injury.

Because of these characteristics, researchers have been looking at the proteins as potential therapies for central nervous system conditions such as Parkinson’s. The full scientific name for MANF proteins is mesencephalic astrocyte-derived neurotrophic factor proteins.

The main idea behind using neurotrophic factor proteins as Parkinson’s treatments is they may be able to rescue the dopamine-generating nerve cells that have deteriorated in the disease.

But MANF Therapeutics said MANF proteins may not only be able to rescue dopamine-generating nerve cells but also increase dopamine release — a significant improvement over other approaches. Scientists have been doing preclinical-trial studies of MANF proteins as a possible treatment for glaucoma as well as Parkinson’s.

In a recent study, researchers compared the effects of administering different neurotrophic factor proteins, including MANF, to a specific region of the brains of healthy rats.

The research, “Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Elevates Stimulus-Evoked Release of Dopamine in Freely-Moving Rats,” appeared in the journal Molecular Neurobiology.

A week after the treatment, the brain cells of the rats that received MANF proteins were releasing a lot more dopamine in response to stimulus than animals treated with other neurotrophic factor proteins or a placebo.

“Although the cellular mechanisms remain to be clarified, knowing the biological effects of exogenously administrated NTFs [neurotrophic factor proteins] in [an]intact brain is an important step towards developing novel neurotrophic treatments for degenerative brain diseases,” the researchers wrote.

“These data are significant because they propose a unique mechanism of action for MANF in Parkinson’s disease that provides a rationale for potentially improved treatment efficacy with MANF versus other neurotrophic factors in development,” MANF Therapeutics said in a press release.

6 comments

  1. Steven says:

    Could this be used in combination with fgf-1 and stem/dopamine cell replacement? I am not a doctor just someone w PD that is curious about potential great things!

  2. M.A. Collins says:

    Assuming peripheral rather than ICV administration as in the rats, does MANF penetrate the BBB to act on its receptors in nigral cells (and are MANF receptors sufficently expressed there)? Probably does not get across the barrier readily…might be better to develop a small MANF receptor agonist that does! Medicinal chemistry, yea!

    • WG says:

      MAC, take a look at how herantis pharma and renishaw are accomplishing getting a near identical protein to the brain. convection enhanced deivry of CDNF

    • Alice Melão says:

      The study presented here is a preclinical study conducted in mice. The therapeutic strategy has not been approved to be teste in humans.

  3. WG says:

    Dave, Herantis Pharma, out of Finland, is conducting a first of its kind study using tech borrowed from Renishaw Plc to administer CDNF which is nearly identical to MANF. They are still recruiting if you live over there. If their method of administration prove safe, and shows effect, there will be a larger study to come, and you can bet Amarantus Bioscience/MANF Therapeutics will launch a study using MANF. Results from Herantis trial (in terms of adverse effects) should start to become known to the research community this year. I would expect a similar study of MANF to start recruiting in late 2019, likely with a site in the U.S.

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