Presentation Title

Pharmacological treatments of a fruit fly model of muscular dystrophy

Faculty Mentor

Lori L Wallrath PhD, Margaret R Ketterer

Start Date

23-11-2019 8:00 AM

End Date

23-11-2019 8:45 AM

Location

113

Session

poster 1

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

Emery-Dreifuss muscular dystrophy (EDMD) is a rare type of muscular dystrophy caused by mutations in the human LMNA gene. The LMNA gene encodes lamins, filamentous proteins that line the inside of the nuclear envelope. To understand the molecular basis of the disease, fruit fly models were made. These models have mutations in the fruit fly Lamin C gene that correspond to disease-causing mutations in the human LMNA gene. The fruit flies develop muscular dystrophy and have reduced motility and viability. Prior studies showed that the fruit fly muscles expressing mutant Lamin C had destabilized microtubules and altered redox status. The goal of my project was to determine if paclitaxel, a drug that stabilizes microtubules, and pamoic acid, a compound that inhibits malic enzyme that is predicted to promote redox homeostasis, suppress the muscle defects. Neither drug treatment increased larval motility relative to wildtype; however, pamoic acid was trending towards significance. Paclitaxel treatment was detrimental to adult viability for flies expressing wild-type Lamin C. Pamoic acid, which reduces NADPH production, suppressed the lethality caused by mutant Lamin C. Therefore, pamoic acid is a potential therapeutic agent for EDMD. The knowledge of effective pharmacological treatments could potentially provide new avenues for therapy.

This document is currently not available here.

Share

COinS
 
Nov 23rd, 8:00 AM Nov 23rd, 8:45 AM

Pharmacological treatments of a fruit fly model of muscular dystrophy

113

Emery-Dreifuss muscular dystrophy (EDMD) is a rare type of muscular dystrophy caused by mutations in the human LMNA gene. The LMNA gene encodes lamins, filamentous proteins that line the inside of the nuclear envelope. To understand the molecular basis of the disease, fruit fly models were made. These models have mutations in the fruit fly Lamin C gene that correspond to disease-causing mutations in the human LMNA gene. The fruit flies develop muscular dystrophy and have reduced motility and viability. Prior studies showed that the fruit fly muscles expressing mutant Lamin C had destabilized microtubules and altered redox status. The goal of my project was to determine if paclitaxel, a drug that stabilizes microtubules, and pamoic acid, a compound that inhibits malic enzyme that is predicted to promote redox homeostasis, suppress the muscle defects. Neither drug treatment increased larval motility relative to wildtype; however, pamoic acid was trending towards significance. Paclitaxel treatment was detrimental to adult viability for flies expressing wild-type Lamin C. Pamoic acid, which reduces NADPH production, suppressed the lethality caused by mutant Lamin C. Therefore, pamoic acid is a potential therapeutic agent for EDMD. The knowledge of effective pharmacological treatments could potentially provide new avenues for therapy.