Originally published on January 18, 2013.

Cure SMA is dedicated to creating a treatment and cure for Spinal Muscular Atrophy by funding and advancing a comprehensive research program, including drug discovery programs to make practical new therapies.   Dr. Rubin’s project at Harvard University is the first of three drug discovery awards that will be given by Cure SMA in the next few months.

Description of Cure SMA Funded Project: 

A patient derived motor neuron screen to identify novel SMA Therapeutics.

Objective: To identify novel SMA therapeutics by using patient-derived motor neurons for drug discovery and preclinical testing.

Research Strategy: The researchers have made induced pluripotent stem cells from Type I and Type II SMA patient skin biopsies, and produced large numbers of motor neurons that can be used to model SMA. They will use these motor neurons in a screen for drugs that increase SMN levels. The researchers will test the candidate drugs in a 35 cell line panel that includes motor neurons from different patients and different SMA types.

Significance: By using human motor neurons to screen for new SMA drugs, the researchers hope to identify compounds that can increase functional SMN levels in the cell type most affected by the disease. They will prioritize compounds that are already approved for use so they can move through the development pipeline more quickly. The researchers will test the candidate compounds across a panel of SMA patient-derived cells so that they can identify drugs that are effective across many genetic backgrounds and disease severities. The researchers hope that this innovative approach will lead to the discovery of drugs that are mechanistically unique so that they may be used in addition to the therapies that are currently being developed. These cell lines can also help assess existing SMA drug candidates.
This current award to the Rubin lab in The Department of Stem Cell and Regenerative Biology at Harvard University is for one year for $150,000 with the goal of conducting cell-based screening in human motor neurons for new SMN inducing drug candidates. Subsequent funding to advance any newly identified molecules towards an Investigational New Drug application with the FDA will be evaluated by our TAC through our next planned funding cycle in Preclinical SMA Drug Development in 2014.

The SMA Drug Pipeline: 

We now have 13 SMA drug programs in development, including 3 in clinical trials. This pipeline has expanded from just 4 programs 5 years ago. Cure SMA has funded half of all the ongoing drug programs for SMA. Our research approach funds programs at early stages, and then partners with companies to take them through clinical trials. Supporting multiple programs gives different approaches for a SMA therapy, which increases the chances of success and accelerates the timeline to a treatment and cure.

Dr. Rubin’s Profile:

Who are you?
I received my PhD in Neuroscience from The Rockefeller University and completed postdoctoral fellowships in Pharmacology from Harvard Medical School and in Neurobiology from Stanford University School of Medicine. I have worked both in academia and in industry, first as a Project Leader at Athena Neurosciences (now Elan Pharmaceuticals) and later as Chief Scientific Officer of Curis, a Cambridge biotechnology company. At Curis, I directed a project that identified the first small molecule hedgehog antagonists. One of these, Erivedge, was recently approved by the FDA to treat advanced basal cell carcinoma

What is your current role in SMA Research?
I am currently Professor of Stem Cell and Regenerative Biology at Harvard University and Director of Translational Medicine at the Harvard Stem Cell Institute. Much of my effort is devoted to identifying therapeutics for orphan neural disorders such as Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis, using new kinds of stem cell-based screens. My lab also explores different chemical biology approaches for manipulating cell fate. Some of this work has been published recently in Cell, Cell Stem Cell, Nature Chemical Biology, Developmental Biology, and Science.

Also, working on the project is Dr. Maureen Lynes in the Rubin Laboratory. Dr. Lynes received her PhD in Cellular and Molecular Physiology at Tufts Medical School, and joined the Rubin laboratory as a post-doctoral fellow in 2011.  Since joining the lab, she been interested in using SMA patient iPS cells as a tool for identifying SMA therapeutics as well as for studying SMA pathogenesis.

Funding for New Drug Discovery Programs

Cure SMA has been investing in and advancing drug research since 2000. The goal of drug discovery funding at Cure SMA is to build a large and diverse therapeutic pipeline to maximize the chances for success in finding a treatment for SMA. Cure SMA has been involved in funding half of all the ongoing SMA drug programs to date. New awards in the current round will focus on providing critical funding for early-exploratory projects assessing novel therapeutic approaches for SMA.

The Cure SMA research funding philosophy is based on expert and independent oversight of research projects. This approach ensures that Cure SMA funds only the most promising research, and that funded projects are run in a professional and efficient manner under the guidance of world-class experts.