# Neural Mechanisms Driving Comorbid Parkinson's and Melanoma

> **NIH NIH F31** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $48,974

## Abstract

Project Summary/Abstract
A series of epidemiological studies have shown that people with Parkinson’s disease (PD) have a significantly
higher risk of developing melanoma and vice-versa. However, research on this comorbidity is sparse. One
possible point of convergence lies in the sympathetic nervous system (SNS). Studies have shown that activating
sympathetic axons residing in breast adenocarcinomas increases cancer growth and metastasis. Extending this,
our preliminary data suggest that mice implanted with melanoma allografts and carrying a knock-in form of the
LRRK2-G2019S mutation, the most common genetic contributor to PD, have enriched populations of
sympathetic axons in their tumor microenvironment. Therefore, I hypothesize that a PD environment
produces an altered melanoma response by regulating the activity and innervation of sympathetic axons
in the tumor microenvironment. To investigate this, I am first characterizing melanoma progression and its
neural microenvironment in WT and LRRK2-G2019S-knock in (GSKI) mice. The data show that the extent and
pattern of melanoma growth is altered significantly in GSKI mice and that immunolabeled tumors show altered
patterns of innervation, macrophage infiltration and angiogenesis. These and additional data will be used to
establish the conditions and timing for testing whether LRRK2-G2019S-mediated alterations in melanoma growth
lie downstream of local sympathetic axonal activity and to ascertain whether positive results can be reversed by
inhibition of LRRK2 kinase activity, which is significantly elevated with the G2019S mutation. Studying the
downstream effects of sympathetic axonal activity and innervation in a tumor microenvironment will create a
fuller understanding of the neural mechanisms connecting PD and melanoma.

## Key facts

- **NIH application ID:** 10880446
- **Project number:** 5F31CA268947-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Pamela Del Valle
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2022-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880446

## Citation

> US National Institutes of Health, RePORTER application 10880446, Neural Mechanisms Driving Comorbid Parkinson's and Melanoma (5F31CA268947-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10880446. Licensed CC0.

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