DNSP-11
Dopamine neuron stimulating peptide-11, an 11 amino acid peptide from the GDNF pro-region
Written by Aaron CuhaReviewed Sep 2026
Also known as: Dopamine neuron stimulating peptide-11, GDNF propeptide, proGDNF peptide
An 11 residue peptide cut from the precursor of GDNF, the growth factor that failed to help Parkinson disease in trials because it could not be delivered. In rats and a small number of macaques it raises dopamine turnover and protects dopamine neurons, including after intranasal dosing. No human has received it.
Overview
Glial cell line-derived neurotrophic factor (GDNF) keeps dopamine neurons alive in every animal model of Parkinson disease it has been tried in, and in people it has been a disappointment, largely because a 15 kilodalton protein does not reach the striatum from anywhere it can be safely put. DNSP-11 is one attempt around that problem: an 11 amino acid amidated peptide that a single American neuroscience group (Bradley, Gash and Gerhardt and colleagues) proposed is cleaved from the pro-region of the GDNF precursor, and which in their hands has GDNF-like effects on dopamine neurons despite not binding GDNF's receptor.
No human has received DNSP-11. A PubMed search finds no human study and ClinicalTrials.gov holds no registered trial under any of its names. What exists is a series of NIH funded rodent and cell papers from one laboratory, plus one macaque study. In the 2010 PLoS One paper, DNSP-11 supported survival and neurite outgrowth of fetal midbrain dopamine neurons in culture, protected a dopaminergic cell line from 6-hydroxydopamine, and after a single injection into the substantia nigra of normal rats raised resting dopamine and its metabolites for up to 28 days; in 6-hydroxydopamine lesioned rats it improved apomorphine induced rotation and raised nigral dopamine. A 2014 follow up found no change in evoked dopamine release by microdialysis four weeks after a single nigral dose, a regional increase by chronoamperometry at two weeks, no change in locomotor activity, and ERK1/2 phosphorylation in a dopaminergic cell line. Two methods papers then showed that repeated intranasal DNSP-11 reaches the rat brain within 30 minutes, raises dopamine turnover at 300 mcg, and partially protects lesioned rats, and that repeated intranasal dosing in awake rhesus macaques over 10 weeks changed striatal dopamine metabolites without observed adverse behaviour or weight loss.
DNSP-11 has no regulatory status anywhere, has never been submitted to a regulator, and the group's work has not been reproduced by an independent laboratory in the published literature we could find.
Mechanism of action
In people, nothing has been measured. In cells and rodents, DNSP-11 does not appear to act through the canonical GDNF receptor complex of GFRalpha1 and RET; the 2010 paper notes its effects on cell lines that GDNF does not protect, and the 2014 paper reports ERK1/2 phosphorylation in a dopaminergic cell line as a candidate signalling step. It blocks staurosporine and gramicidin induced death in nutrient deprived cells and prevents cytochrome c release from mitochondria, which the authors read as a mitochondrial protective action, and a 2011 stability study shows it is soluble, stable for a month and, unlike GDNF, does not bind heparin, which should let it diffuse in tissue. No receptor for DNSP-11 has been identified. The peptide is also taken up into neurons after nigral injection, by an unknown route.
Human evidence
None. No study has given DNSP-11 to a human, and no clinical trial has ever been registered.
What this does not tell you: There is no human data of any kind, so nothing can be said about safety, dose, delivery or effect in a person. The animal work comes from a single laboratory and its 2014 paper reports mixed findings; independent replication was not located. Intranasal delivery to the brain works differently in a 300 gram rat than in a human, and the macaque study was a methods paper with small groups. GDNF itself, which has far stronger animal data, did not produce benefit in controlled human trials of Parkinson disease, and DNSP-11 would need to solve the same delivery problem before anything else.
Reading the research record
DNSP-11 is a university discovery that has not left the university. Every paper on it comes from one group of collaborating authors (Bradley, Gash, Gerhardt and colleagues), funded by the National Institutes of Health, over a span from 2010 to 2019. That is not a criticism; it is where early neuroscience lives. But it means there is one group's word for every finding, and the group's own 2014 paper found less than its 2010 paper did on some measures. The existence of the pro-region peptide in the brain was inferred from processing site predictions; a 2019 antibody paper from the same group reports immunoreactivity in rat brain consistent with it.
The intranasal work is the interesting part, because delivery is exactly what the DNSP-11 papers themselves identify as GDNF's clinical problem: a large protein that does not distribute to where it is needed. An 11 residue peptide that reaches rat striatum from the nose within half an hour is a real advance in an animal, and whether it happens in a primate skull is what the 2018 macaque study began to ask. Nobody has taken it further, no company has licensed it into a clinical programme that we could find, and no trial exists. Anything sold as DNSP-11 is a peptide with two rodent efficacy papers and a macaque methods study behind it and nothing else.
The evidence, charted
Fig. 1 · evidence composition
0of 5 citations (0%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 5 distinct years, 2010 to 2018, counted from the citation list on this page. The newest citation on file is from 2018, more than five years ago; the published record may have gone quiet.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Not approved
CA
Not approved
Approved in 1 of 4, prescription route in 0, not approved in 3. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Key studies & citations
- Animal2010
Dopamine neuron stimulating actions of a GDNF propeptide
In culture, DNSP-11 supported survival and neurite outgrowth of fetal midbrain dopamine neurons and protected MN9D cells from 6-hydroxydopamine. In rats, a single nigral injection raised resting dopamine and metabolites for up to 28 days, and in 6-hydroxydopamine lesioned rats improved apomorphine induced rotation and raised nigral dopamine. Effects appeared independent of the GFRalpha1 receptor. NIH funded.
PLoS One - Animal2014
Dynamic changes in dopamine neuron function after DNSP-11 treatment: effects in vivo and increased ERK 1/2 phosphorylation in vitro
Single nigral dose in rats: no change in potassium or amphetamine evoked dopamine release by microdialysis at 4 weeks; increased potassium evoked release in striatal subregions by chronoamperometry at 2 weeks; no change in locomotor activity. ERK1/2 phosphorylation in MN9D cells. A mixed result from the same laboratory. NIH funded.
Peptides - Animal2015
Methodology and effects of repeated intranasal delivery of DNSP-11 in a rat model of Parkinson's disease
Repeated intranasal dosing for 3 weeks raised dopamine turnover in striatum and substantia nigra of normal rats at 300 mcg; in 6-hydroxydopamine lesioned rats it reduced amphetamine induced rotation at 2 weeks and spared tyrosine hydroxylase positive neurons in one nigral subregion. Radiolabelled peptide reached striatum and nigra within 30 minutes of a nasal dose. NIH funded.
Journal of Neuroscience Methods - Animal2018
Methodology and effects of repeated intranasal delivery of DNSP-11 in awake Rhesus macaques
Repeated intranasal dosing with dose escalation over 10 weeks in awake rhesus macaques, including MPTP treated animals. Bilateral changes in striatal dopamine metabolites without observed adverse behavioural effects or weight loss. A methods and proof of concept study; group sizes are small. NIH funded.
Journal of Neuroscience Methods - In vitro2011
Evaluation of the physical and in vitro protective activity of three synthetic peptides derived from the pro- and mature GDNF sequence
DNSP-11, DNSP-5 and DNSP-17 are soluble, stable for a month under a range of conditions, and DNSP-11 does not bind heparin, unlike GDNF, which should aid diffusion in tissue. DNSP-11 protected HEK-293 cells dose dependently from staurosporine and 3-nitropropionate toxicity. NIH funded.
Neuropeptides
Frequently asked questions
Has DNSP-11 been tested in humans?
No. There is no published human study and no clinical trial has ever been registered. Every finding comes from rats, cell lines and one small study in rhesus macaques.
What does it do in animals?
In rats, a single injection into the substantia nigra raised dopamine and its metabolites for weeks and improved motor behaviour in a lesion model, and repeated intranasal dosing raised dopamine turnover and partially protected neurons. A follow up found no change in evoked dopamine release by one method and a regional increase by another, with no change in locomotor activity. In macaques, 10 weeks of intranasal dosing changed striatal dopamine metabolites without observed adverse effects.
Is it the same as GDNF?
No. GDNF is a 15 kilodalton protein; DNSP-11 is an 11 amino acid peptide proposed to be cut from GDNF's precursor. It does not appear to act through GDNF's receptor and no receptor for it has been identified. GDNF itself has failed to show benefit in controlled human trials of Parkinson disease, mainly because of delivery.
Does intranasal DNSP-11 reach the brain?
In rats, radiolabelled peptide was found in the striatum and substantia nigra within 30 minutes of a nasal dose. Whether that happens across the much longer distances of a human head has not been tested; the macaque study measured dopamine metabolites, not peptide distribution.