The researchers have observed abnormalities of motor axon growth and myelination in SMA patient autopsy tissue and SMA mice. The primary research question is what is the basis of this abnormal axonal development in SMA? They hypothesize that impaired axonal development is due to SMN deficiency in both in motor neurons and Schwann cells and the objective of the project is to establish whether SMN deficiency in Schwann cells is an important contributor to SMA disease manifestations. Schwann cells are the principle glia or support cells of motor neurons in the peripheral nervous system (PNS).
The researchers plan to analyze the morphology and gene expression profiles of axons, Schwann cells, and myelin in severe SMA mice and in SMA mice where SMN expression has been selectively increased in motor neurons. They will then generate and analyze novel SMA mice in which SMN has been selectively restored to Schwann cells. Finally, they will evaluate the combination of SMN expression in both motor neuron and Schwann cells.
Earlier this year, FSMA's Advisory Boards met to evaluate new research funding for 37 basic research grant applications and 7 drug discovery projects for SMA. The organization is planning to award $1.4 Million in new research funding over the next few months. This new round of research funding will be allocated into three areas: 1) Basic Research to understand the disease and provide ideas for drug making, 2) Drug Discovery to develop new SMA therapies, and 3) Clinical Research to help test new drugs effectively and to improve care for patients.
This grant to Dr. Sumner at Johns Hopkins University will help us understand the exact nature of the defects in the both the spinal cord and in the periphery in SMA. This will help answer the key basic research question of what tissues are affected by reduced SMN protein?
The basic research that Families of SMA has funded, through 145 research grants to 75 institutions around the world, has delivered major discoveries:
-We know the cause of SMA. Which means we can develop treatments that correct the underlying cause of the disease rather than just reduce symptoms.
-We identified a back-up gene for SMA. Which means we have a straightforward drug target already in the body: a built-in switch for new therapies to work on.
Using this knowledge, we now have 3 clinical trials testing new SMA therapies, and an additional 10 programs in earlier stages of the drug development pipeline.