Originally published on February 27, 2014.

Cure SMA is leading the way to a world without SMA by advancing a comprehensive research program, of which basic research is a key component.  Cure SMA has awarded 79 basic grants for a total of $9,507,612 in the past 10 years. Drs. Laurent and Lutz from Jackson Laboratory will receive $90,000 to support a collaborative project at three centers to explore the use of electrophysiological endpoints in drug testing in mice.

Multi-Center Electrophysiological Evaluation of Clinically Relevant Phenotypes in SMA Mouse Models

Objective: Electrophysiology measures the activity of the motor nerves controlling the muscles by non-invasive methods like skin-adhesive electrodes. We will show that these techniques, frequently used on patients, can also reliably identify the disease progression in SMA mouse models.
Research Strategy: Our multicenter collaboration will consist of providing three research centers with groups of virtually identical mice, all modeling SMA. The three centers will measure in parallel the electrophysiological signals on these mice and compare data. The three centers include: 1) Dr. Laurent Bogdanik at The Jackson Laboratory, 2) W. David Arnold, MD at The Ohio State University, and 3) Seward Rutkove, MD at Beth Israel Deaconess Medical Center / Harvard Medical School.
Significance: Standard research procedures will be provided to the research community to allow for the comparison of different therapeutic strategies in SMA mouse models, across different institutes. Current mouse models lack symptoms that can be easily measured and resemble patient symptoms. By establishing a procedure to measure neuronal activity, this project will offer a powerful and clinically relevant way to follow symptoms in mice.

Meet Dr. Laurent:

Who are you?
My very first research endeavor was to understand how nerves and muscles communicate using the fruit fly as a model. I met with the patients and families of the foundation supporting my work, and I could feel their sense of urgency to find therapies. This made me worry that fruit flies were too different from humans, to allow for a rapid translation of research findings into potential cures. Moving to the Jackson Laboratory, I started to research on mice, whose genes, muscles, and nerves are very similar to ours. I was able to dissect the molecular mechanisms at play in various human conditions, such as myasthenic syndromes or peripheral neuropathies.  Mice are an essential step in the long process of drug development, but sometimes mice with mutations similar to disease-causing mutations did not have the same symptoms as the patients. Thus, questions arise on whether they are really “up to the job”, which commanded me to spend more energy to improve our mouse models.

How did you first become involved with SMA research?
The Jackson Laboratory is the host for an impressive “Repository” of research mice originating from laboratories across the word. Among these are many mouse models for SMA.  Working for the Director of the Repository, Dr. Cathleen Lutz on SMA, a research topic dear to her heart, it became clear that SMA mouse models should be our priority.  With the advent of the first genetic therapies, appropriate pre-clinical models were needed to answer many questions. 

What is your current role in SMA research?
We created a new mouse model with a later onset of the disease than the models already available, to better study type II/III SMA. In order to focus on symptoms similar to the clinical presentation of SMA, I developed an electrophysiology system, similar to the ones used in the clinic, that records the communication between nerves and muscles, impaired in SMA. With renowned SMA clinicians, Drs. Seward Rutkove and William Arnold, we are now determining the best ways to perform and analyze these recordings in mice, to study the progression of the disease and efficacy of potential drugs.

2014 Cure SMA Research Mission and Funding

The overall mission at Cure SMA is a world without SMA. Making this happen requires scientific research investments. Thus, our main research goal at Cure SMA is to accelerate the discovery of an effective treatment and cure for SMA by funding and advancing a comprehensive research program, including:
•    Basic Research to reveal the best ways of making SMA drugs,
•    Drug Discovery to make new drugs,
•    Developing Clinical Trial infrastructure to help test new drugs, and
•    Clinical Care Research to improve the quality of life in SMA patients.

In addition to the basic research funding announced in this edition of Compass, Cure SMA will invest in more research in 2014 to advance our vision of a world without SMA. Please be on the lookout for two upcoming Requests for Proposals (RFPs) for additional research funding from Cure SMA in 2014 in the following research areas: 1) Drug Discovery – Overseen by the Translational Advisory Council, and 2) Clinical Care – Overseen by the Medical Advisory Council.