Abstract Details

Title Effect of 3,4-diaminopyridine phosphate in symptomatic SOD1-G93A mice

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 383

Objective

To study the effect of 3,4-diaminopyridine phosphate (3,4-DAPP) on body weight, grip strength, neurological score and survival in symptomatic SOD1-G93A mice.

Background According to dying back hypothesis of Amyotrophic lateral sclerosis (ALS), neuromuscular junction (NMJ) dismantling plays a crucial role in the onset of disease. Previous studies in SOD1-G93A mice have shown distal axonal and NMJ alterations prior to the onset of clinical symptoms. NMJ integrity depends on the presynaptic release of acetylcholine and clustering of acetylcholine receptors on the muscle plasma membrane to trigger muscle action potentials. 3,4-DAPP increases the release of acetylcholine in the neuromuscular synapse by prolonging the activation of voltage gated calcium channel at the nerve terminal and enhances neuronal excitability, improves neuromuscular and central synaptic transmission.

Design/Methods

SOD1-G93A mice were divided into three separate groups and their baseline bodyweight and grip strength was recorded. 3,4-DAPP was administered at 0, 8, and 16 mg/kg to individual groups for 5 days/week beginning at 90 days of age. Thereafter, body weight, grip strength by inverted wire screen, neurological score developed by ALS therapy development institute (ALSTDI) and survival was recorded every 7 days for total of 160 days.

Results

The variables between the groups when analyzed using a 2-way Analysis of Variance (ANOVA) showed that body weight had F value of 0.561 (p=0.910), grip strength had F value of 0.656 (p=0.835), neurological score had F value of 0.402 (p=0.778) and survival Chi square was 0.2819 (p=0.8685).

Conclusions

Our study showed that 3,4-DAPP had no influence on body weight, grip strength, neurological score and survival in symptomatic SOD1-G93A mice. To further investigate the utility of 3,4 DAPP in ALS; larger animal studies, longer treatment times and/or earlier in life treatment may be required.

Authors/Disclosures
Swathi Beladakere Ramaswamy, MD PRESENTER	Dr. Beladakere Ramaswamy has nothing to disclose.
	No disclosure on file
Stanley J. Iyadurai, MD, PhD, FAAN (Johns Hopkins All Children's Hospital/Catalyst)	Dr. Iyadurai has received personal compensation for serving as an employee of Catalyst Pharmaceuticals. Dr. Iyadurai has received stock or an ownership interest from Catalyst Pharmaceuticals.
Raghav Govindarajan, MD, FAAN (HSHS St. Elizabeth Medical Group)	Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MT pharma. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catalyst. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Govindarajan has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MT pharma . Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Catalyst. Dr. Govindarajan has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Argenx. Dr. Govindarajan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biohaven. Dr. Govindarajan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for UCB. Dr. Govindarajan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Takeda. Dr. Govindarajan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Abbvie. The institution of Dr. Govindarajan has received research support from Band of Hope . The institution of Dr. Govindarajan has received research support from Alexion. Dr. Govindarajan has received publishing royalties from a publication relating to health care.
Richard J. Barohn, MD, FAAN (University of Missouri)	Dr. Barohn has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for NuFactor. The institution of Dr. Barohn has received research support from FDA OPD R01. Dr. Barohn has received intellectual property interests from a discovery or technology relating to health care.

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