“Role of Neurofilaments and Mitochondria in the Pathogenic Cascade of ARSACS : Relevant Biomarkers for Therapeutic Development” – Dr. Heather Durham

In Research in 2016 by ARSACS

The research project has the following  specific objectives : Aim 1. Determine the effect of sacsin domains Aim 1.1:  Determine the effect of sacsin domains on IF architecture and IF bundling in ARSACS models.  Aim 1.2: Determine which domains in combination are essential to rescue the ARSACS phenotype. Aim 2. Develop a peptide drug using neuroprotective sacsin domains.  Aim 2.1: Optimize …

Investigating the Link Between Impaired Mitochondrial and Calcium Dysregulation in SACS/Purkinje Neurons – Dr. Francesca Maltecca

In Research in 2016 by ARSACS

The research project has three specific objectives: to test the distribution of mitochondria in distal dendritic branches of Sacs primary PCs; to evaluate dysregulation of Ca2+ homeostasis in Sacs mice and finally to test the efficacy of targeted therapy in Sacs mice. Duration: Second year of a two year project Grant: $100,000 Contact: Dr. Francesca Maltecca, Phd, Neurogenomics Unit(4A2) San Raffaele …

“Elucidating Sacsin Function Through Genetic Interaction Maps”- Dr.Mohan Babu

In Research in 2016 by ARSACS

Aim 1- Mapping GI network of ARSACS-associated SACS target using CRISPR 1.1. Quantitative readout for scoring GIs 1.2. GI validation and benchmarking Aim 2 – Characterizing ARSACS-linked SACS pathways for function discovery Duration: one year Grant: $100,000 Contact: Dr.Mohan Babu, Asst. Professor CIHR New Investigator,Department of Biochemistry University of Regina Saskatchewan SK S4S 0A2 Tel:(306)-585-4192; Email: mohan.babu@uregina.ca Interesting, right? Share …

Rescuing mitochondrial division in ARSACS by CIDR”- Dr. Stefan Strack

In Research in 2016 by ARSACS

Aim 1. Generate and characterize mice with chemically inducible mitochondrial division in Purkinje neurons (L7-CIDR mice). Aim 2. Evaluate rescue of Purkinje cell degeneration and motor deficits in SACS-/- mice by inducible mitochondrial division. Duration: two years Grant: $100,000 per year Contact: Dr.Stefan Strack, Professor of Pharmacology University of Iowa Carver College of Medicine 2-452 BSB, 51 Newton Rd. Iowa …

“Cerebellar Cells Derived From Induced Pluripotent Stem Cells in 3D Culture Generated From ARSACS Patients As Faithful Disease Model”- Dr.Slaven Erceg

In Research in 2016 by ARSACS

Objective 1. To generate in vitro disease model by creating ARSACS disease- specific cerebellar cells via iPSC from patients and healthy individuals as controls which will serve as a tool to depict disease-specific molecular markers. Objective 2. The comparative functional analysis between control and patient derived cerebellar cells (Purkinje and granule cells) will include molecular, cellular studies focused on detection …

“Characterizing and Ameliorating Axonal Transport Defects in ARSACS Mice”- Dr. Thomas Schwartz

In Research in 2016 by ARSACS

The objective is to identify compounds that will improve axonal transport in neurons carrying the mutation. The compounds we will survey are ones with a known mechanism of action and thus will identify cellular signaling pathways with the potential to overcome the transport deficits. These pathways are likely to include drug‐able targets that could ultimately serve as a point of …

“Sacsin Chaperone Activity” – Dr.Jason Young

In Research in 2016 by ARSACS

The research project is to examine the ARSACS mutations in the J-HEPN fragment of sacsin, to engineer Hsc70 to potentially identify sacsin-directed substratesand to address whether sacsin promotes degradation of neurofilament heavy subunit (NFH) Duration: one year Grant: $40,431 Contact: Dr. Jason Young, Associate Professor Department of Biochemistry Francesco Bellini Life Sciences Building, 3649 promenade Sir-William-Osler, Office: Room 467; Lab: …

“High-throughput strategy to identify large domains of Sacsin” – Dr Kalle Gehring

In Research in 2016 by ARSACS

The greatest bottleneck in structural studies of Sacsin is the preparation and screening of fragments of thousands of Sacsin constructs with different boundaries, different mutations, and sequences from different species. To overcome this, we have developed a high-throughput strategy that relies on chemical DNA synthesis to prepare medium-sized libraries (mixtures) of Sacsin protein fragments. These are analyzed by gel filtration …

“Analyzing the influence of ARSACS mutations on the function of human neurons derived from induced pluripotent stem cells.” – Dr. Peter McPherson and Dr. Edward Fon

In Research in 2016 by ARSACS

The researchers will use genome editing of hiPSCs to test the hypothesis that point mutations in the SACS gene lead to alterations in mitochondrial function and neurofilament organization in neurons derived from ARSACS patients. Specific aim 1: Generate genome-edited neurons from fibroblasts of ARSACS patients. Specific aim 2: Examine the influence of sacsin mutations on the cell biological properties of …

“Design and Synthesis of Second Generation Voltage-gated Potassium Channel Modifiers for Correcting Neuronal Dysfunction as a Treatment Strategy for ARSACS” – Talon pharmaceuticals

In Research in 2016 by ARSACS

The overall objective of the project is to devel+op TPS-100 as a first treatment of ARSACS and to identify a second generation drug based on efficacy and knowledge of receptor pharmacology of TPS-100. Our goal is to synthesize a directed library of compounds with varying Kv channel pharmacology with the goal of enhancing activity at Kv1.2, 1.3, 1.4 relative to …