Udai Pandey, associate professor at the Children’s Hospital of Pittsburgh in Pennsylvania, was awarded an MDA research grant totaling $300,000 over three years to identify new drugs for ALS (amyotrophic lateral sclerosis) caused by a mutation in the FUS gene.

Please describe your current research.

We are interested in understanding the basic mechanisms of FUS-mediated ALS and are working to identify drugs that can suppress symptoms associated with ALS. Our MDA-funded ongoing studies are critical for translating a pool of drug hits into therapeutic candidates that can be tested in animal models of FUS-ALS.

We recently performed a large small molecule screen using a library of 400,000 drugs in a yeast model of FUS-mediated neurodegeneration and identified about 80 drugs that strongly suppress toxicities associated with FUS. We are proposing to follow up on these positive compounds in a fly model of FUS as well as in nerve cells created from ALS patient stem cells. Currently, there are no drugs available specifically for FUS ALS patients and our proposed pre-clinical studies are likely to help in identifying drugs for clinical trials.

Is this your first MDA grant?

This is my first MDA research grant. I completed my postdoctoral training with the support of an MDA career developmental grant award. MDA support has been critical and a driving force for establishing our ALS research program.

What is your focus within the ALS field, and why is it important?

We are interested in understanding the molecular mechanisms of FUS-mediated ALS. We’ve developed cellular and animal models to determine how pathogenic mutations in FUS cause motor neuron degeneration.

A FUS mutation can lead to an aggressive and juvenile form of ALS. This protein is similar to another ALS-causing RNA binding protein TDP-43. This area is important as it can help in understanding how defective RNA metabolism leads to motor neuron degeneration.

What is the expected outcome of this research?

We expect to develop robust cellular and animal models that would be useful for studying basic ALS mechanisms.

How will your research lead to treatments and cures?

Our small molecule screening project could help in identifying drugs that might be useful for testing in vertebrate ALS models and ultimately in human clinical trials.

Does your work have any potential implications for other disease fields?

Degeneration of motor neurons has been observed in several human neurological diseases. Whatever we learn from our studies may have potential implication for other neurological disease fields.

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