Jefferson University Hospitals

Research

Working Together Today to Improve Lives Tomorrow

Despite the work of researchers around the world, ALS is still a poorly understood disease. Because there are so many unknowns surrounding the disease, the most important research is conducted in labs, instead of human trials. We believe that once we understand the basic, biological cause of ALS, we will be able to begin developing effective therapies.

The research activities of our team are geared toward working together to discover novel information that can be used to create a more comprehensive understanding of the basic biological causes of ALS and to identify and validate novel therapeutic  targets. Such information can provide much needed support towards the development of  effective therapies that improve lives.

No disease is incurable, we just haven’t figured this one out yet.

- Michael Fulginiti, 1957 - 2016
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Current Initiatives

Tractable Models for C9orf72-linked ALS

An aberrant expanded DNA sequence in the C9orf72 gene is the most prevalent gene associated with  amyotrophic lateral sclerosis and frontotemporal dementia. 

This expanded DNA region leads to the production of neurotoxic RNA and protein through an unconventional translation of the repetitive RNA. We are developing cell-based, cell-free, and animal experimental models that afford quantitative as well as qualitative assays for understanding these neurotoxic mechanisms in efforts to identify preventative therapeutic strategies.

Challenges for a Successful Pharmacotherapy in ALS

Amyotrophic lateral sclerosis (ALS) is one of the most devastating and lethal progressive neuromuscular disorders, affecting motor neurons in the spinal cord and motor cortex.

Over 30,000 people are living with this disease in the United States and approximately 6,000 Americans will be diagnosed with ALS this year. Multidrug efflux ABC transporters limit the entry into the brain and spinal cord of a large number of drugs, contributing to the poor success rate of promising drug candidates, and regulate the extrusion of a variety of substances, including catabolites and potential toxic molecules that could be harmful to cells. Modulating the activity and expression pattern of these transporters could therefore improve drug delivery into the brain and spinal cord and affect the overall cellular homeostasis. We are currently investigating how these ABC transporters are regulated in ALS with the ultimate goal of improving pharmacotherapy for this disease.

Propagation of Neurotoxic Proteins in ALS

There is a growing body of evidence that pathogenic proteins may propagate from cell-to-cell in ALS and other neurodegenerative diseases.

We postulate that the propagation or transmission of toxic proteins or nucleic acids could be a modality by which toxic insults spread in disease-afflicted areas in ALS. We are currently testing the hypothesis that transmitted dipeptides transfer injury to both neighboring cells but also to neurons downstream in synaptic circuits using complementary in vitro and in vivo approaches.

Molecular Pathways Leading to Dysfunction at the Neuromuscular Junction in ALS

ALS is currently an incurable paralytic disorder that is caused by motor neuron cell death, which are cells that send impulses to the muscles and control all movements throughout the body.

This loss of communication between the motor neurons and the muscles is one of the hallmarks of ALS. Little is known about the mechanisms by which the many genetic mutations uncovered in ALS lead to an impaired neuromuscular junction. We employ a variety of cellular and animal models to identify the pathogenic mechanisms that lead to this loss of motor neuron-muscle connectivity, with the goal of identifying intervention therapies to maintain muscle strength in patients.

Weinberg ALS Center Research Team

Weinberg ALS Center Research Team


Make An Appointment

Appointments are available every Friday for patients with a confirmed diagnosis of ALS. Diagnostic services are also available. If you have been told you have ALS, or have been asked to see an ALS specialist for a possible diagnosis, we can help. Please call the Jefferson Weinberg ALS Program Manager, Kate Monahan at 215-503-4294 or 215-955-8800.

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Find out how you can support Thomas Jefferson University and Hospitals to make a difference in the research and treatment of ALS.