# Novel Re-engineered L DOPA probiotic therapy for Parkinsons Disease

> **NIH NIH R61** · IOWA STATE UNIVERSITY · 2020 · $224,584

## Abstract

Abstract
 The complex and prolonged disease course exhibited by Parkinson’s disease (PD) first starts with non-
motor disturbances and then slowly progresses to mild-to-moderate motor deficits, ultimately inflicting severe
movement impairment and cognitive decline. Dopamine deficiency resulting from nigrostriatal dopaminergic
neuronal damage ultimately manifests as the cardinal extrapyramidal motor symptoms of rigidity, bradykinesia,
tremors, and postural instability. This proposal addresses one of the greatest challenges facing the current anti-
Parkinsonian therapy of dopamine replacement with the dopamine precursor L-DOPA. Currently, oral tablet
dosing of L-DOPA/carbidopa 3-4 times/day remains the most effective and well-tolerated treatment, one that
significantly improves the motor symptoms and quality of life of patients in the early stages of PD. However, due
to its non-continuous, pulsatile delivery of L-DOPA to the brain, long-term L-DOPA administration causes
deleterious side effects, including L-DOPA-induced dyskinesia (LID) among other motor complications, in the
majority of patients. To achieve sustained symptomatic relief without severe L-DOPA-associated motor
complications, including dyskinesia, we propose that systemic delivery of genetically engineered, chromosome-
integrated, and regulatable L-DOPA-producing probiotic bacteria will avoid fluctuations in plasma L-DOPA levels
and provide a more consistent delivery of L-DOPA to the brain where it can be converted to a continuous supply
of dopamine in the nigrostriatal pathway. Thus, we aim to systematically evaluate the treatment feasibility
and efficacy of this novel microbiome-based platform for the continuous delivery of L-DOPA in relieving
motor symptoms without inducing severe dyskinesia. The scientific premise of the work is supported by key
preliminary data demonstrating that: 1) the genetically reengineered, chromosome-integrated, and regulatable
L-DOPA-producing E. coli Nissle 1917 probiotic strain (EcNrhaL-DOPA) efficiently produce L-DOPA both in vitro and
in vivo than the older plasmid-based system, and 2) oral administration of EcNL-DOPA readily colonizes the mouse
gut, achieves a steady-state plasma L-DOPA level that corresponds to the clinically effective plasma level in PD
patients, and increases L-DOPA and dopamine levels in the brain. To further expand our novel preliminary
results, we will pursue the following specific aims: R61 phase (i) determine the dose-response effect of orally
administered EcNrhaL-DOPA on gut colonization as well as its pharmacokinetic and adaptation profiles in both
C57BL and MitoPark mice; R33 phase (ii) determine the therapeutic efficacy of EcNrhaL-DOPA in the MitoPark and
6-OHDA-lesioned mouse models of PD, and (iii) determine whether sustained delivery of microbial L-DOPA
prevents LID in two mouse models of LID. Our novel therapeutic pipeline strategy involving chronic delivery of
probiotic L-DOPA is expected to transform the dopaminergi...

## Key facts

- **NIH application ID:** 10043372
- **Project number:** 1R61NS112441-01A1
- **Recipient organization:** IOWA STATE UNIVERSITY
- **Principal Investigator:** Anumantha Gounder Kanthasamy
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $224,584
- **Award type:** 1
- **Project period:** 2020-09-01 → 2021-07-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10043372

## Citation

> US National Institutes of Health, RePORTER application 10043372, Novel Re-engineered L DOPA probiotic therapy for Parkinsons Disease (1R61NS112441-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10043372. Licensed CC0.

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