FSMA-Funded Stem Cell Research

FSMA is investing in stem cell research for SMA, and we have made significant progress with our funding.  Cellular transplant therapy is the one possible approach that could result in replacement of motor neurons lost during disease course.  Other approaches are more likely to prevent or stabilize motor neuron loss.    Motor neuron replacement is at the leading forefront of current scientific knowledge, and as such is also quite high risk.   However, this approach allowing for the possibility of replacing lost motor neurons holds great promise for the patients and families in our community. 

Please click here to read the current status of the program in a our recent Drug Discovery Compass.

To advance stem cells to human clinical trials, several types of data is requred:

• efficacy data showing this approach works for SMA
• safety data assessing risk of human exposure
• qualty assurance data showing implementation of standardized clinical grade manufacturing 

Our collaboration team, including  the laboratory of Dr. Keirstead at The University of California, Irvine (UCI), the laboratory of Dr. Kerr at Johns Hopkins, and California Stem Cell, Inc (CSC) is currently working on obtaining all three types of data. Progress in each is described below.

Please click here to see a synopsis of this project by Dr. Hans Keirstead at the University of California, Irvine.

Our past investment in stem cell research, which was devoted to efficacy studies, helped produce two important findings:

• Proof-of-concept experiments showing motor neurons from mouse embryonic stem cells provided therapeutic benefit in a rodent model of motor neuron disease from the Kerr lab (Annals of Neurology, July 2006, 60: 32-44).
• The successful production of motor neurons made from human embryonic stem for therapeutic use in humans from the Keirstead lab (See Figure 1).

In early 2007, FSMA continued our commitment to this program by funding two additional grants to both the Kerr and Keirstead laboratories.  The Keirstead lab received a two-year grant to analyze the previously generated source of high purity motor neurons to prove they behave like actual motor neurons and are fit for use in human clinical trials.  The Kerr lab also received a 2-year grant to demonstrate that the human motor neurons generated in the Keirstead lab provide therapeutic benefit in a large animal model of motor neuron disease.

In a collaboration between Families of SMA, Hans Keirsteand, and CSC, the pivotal animal safety study, required to support an IND application to the FDA to begin clinical trials, was completed in October 2008.

The experiments assessed the safety of motor neuron progenitors derived from human stem cells after transplantation. Data analysis is in the final stages and should be complete by the end of June 2009. There  were no negative outcomes of this safety study, leading to the conclusion that motor neuron replacement should be a safe strategy in the treatment  of diseases such as SMA characterized by motor neuron loss.  These safety studies are the critical step in advancing stem cell therapy into human trials for SMA. 

Finally, CSC has developed methods for the manufacture of clinical grade human motor neurons from human embryonic stem cells.

CSC employs scalable manufacturing protocols to produce and supply the large population of clinical-grade motor neuron progenitors required for the pivotal studies and future human clinical trials.  Therefore, we currently have the team in place to make progress in obtaining both the efficacy and safety data required to move towards human testing.

It is the intent of CSC  to gain approval to begin FDA-approved clinical trials for the use of these cells in development of a cell replacement therapy for SMA Type I.

CSC has recenlty held a pre-IND meeting with the FDA, keeping the project on track for a formal Investigational New Drug (IND) application to begin a Phase I/IIA clinical trial in SMA Type I.  In addition, this stage of the project has included the hiring of a Medical Director and a Clinical Research Coordinator at CSC. The two new positions will be responsible for coordinating the preparation of the above IND application and for overseeing and monitoring the resulting clinical trials. The financial support for these positions came from a grant to CSC from Families of SMA through the generous support of the Dhont Family Foundation. 

See a recent press release by FSMA and CSC discussing the FDA pre-IND meeting.

See the recent press release by FSMA, UCI, and CSC announcing our partnership to advance stem cell therapy in our news section.

Families of SMA understands that the use of stem cells is a controversial subject. As an organization, FSMA is committed to pursuing the most promising treatment possibilities. However, we also understand that ethical and religious issues remove stem cells as an option for some of our families and donors. For that reason, any donor to FSMA may restrict their donation to non-stem-cell-related research. To do this simply indicate - not for stem cell research - when you make your donation.