Abstract Details

Title Hereditary Spastic Paraplegia Modeled in Drosophila Melanogaster

Topic Movement Disorders

Presentation(s) P05 - (-)

Poster/Presentation
Number 050

Objective

Background BACKGROUND: Hereditary Spastic Paraplegia (HSP) is a group of rare inherited neurodegenerative disorders, clinically characterized by progressive weakness and spasticity of the lower limbs. HSP is caused by the disruption of axonal transport near the distal parts of neurons. Two of the most common causes of HSP are due to mutations in the genes Spastin (Spast) and Atlastin (Atl-1).

Design/Methods DESIGN/METHODS: Flies hypomorphic for spast and atl-1 were generated by RNA interference (RNAi). Using the UAS GAL-4 system, selective spatial expression can be tested. The locomotion of both UAS-Spast and UAS-Atl-1 RNAi lines, driven by the ELAV GAL-4, along with appropriate controls, was tested using a climbing assay. 1-day old flies were placed in a graduated cylinder and, after starting from the bottom, the proportion of flies, which climbed above the 17.5cm mark, was recorded over a period of two minutes. Statistical analysis was performed with a t-test.

Results RESULTS: Using 1 day old flies showed that less than 20% of the flies expressing either Spast and Atl-1 RNAi were able to cross the 17.5 cm mark after 2 minutes of recording compared to over 80% for the appropriate genetic control flies. This statistically significant difference was reproduced in 10 experiments. Moreover, the rate of climbing was decreased in the spast and Atl-1 RNAi expressing flies.

Conclusions CONCLUSIONS: Our results suggest that, as is the case in humans, the genes Spast and Atl-1 are responsible for proper locomotion in D. melanogaster and thus are two of the major genes responsible for HSP. Next, we will assess the evolution with time of the motor performance. In addition, we will test potential treatments to rescue the locomotion seen in these flies.

Authors/Disclosures
Francois V. Bolduc, MD, PhD (University of Alberta) PRESENTER	No disclosure on file
Joseph C. Masdeu, MD, PhD, FAAN (Houston Methodist Neurological Institute)	Dr. Masdeu has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Lilly . The institution of Dr. Masdeu has received research support from NIH. The institution of Dr. Masdeu has received research support from Houston Methodist Foundation. The institution of Dr. Masdeu has received research support from Alector. The institution of Dr. Masdeu has received research support from Aviado-Bio. Dr. Masdeu has received publishing royalties from a publication relating to health care. Dr. Masdeu has received publishing royalties from a publication relating to health care. Dr. Masdeu has received personal compensation in the range of $100,000-$499,999 for serving as a Director, Nantz Nal Alzheimer Center with HOUSTON METHODIST NEUROLOGICAL INSTITUTE.
Joseph C. Masdeu, MD, PhD, FAAN (Houston Methodist Neurological Institute)	Dr. Masdeu has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Lilly . The institution of Dr. Masdeu has received research support from NIH. The institution of Dr. Masdeu has received research support from Houston Methodist Foundation. The institution of Dr. Masdeu has received research support from Alector. The institution of Dr. Masdeu has received research support from Aviado-Bio. Dr. Masdeu has received publishing royalties from a publication relating to health care. Dr. Masdeu has received publishing royalties from a publication relating to health care. Dr. Masdeu has received personal compensation in the range of $100,000-$499,999 for serving as a Director, Nantz Nal Alzheimer Center with HOUSTON METHODIST NEUROLOGICAL INSTITUTE.
Stuart D. Cook, MD, FAAN (Rutgers)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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