Clinical Resources
The mission of the SMA Foundation is to accelerate the development of a treatment for SMA. Fulfilling this mission means bridging gaps among research efforts from academia, industry, and government, developing research tools, and making these tools available to the SMA community.
We are pleased to provide information on the following projects and resources to support clinical research and clinical trials in SMA. Links to research tools, data sets and reagents are provided under the following topics:
We are pleased to provide information on the following projects and resources to support clinical research and clinical trials in SMA. Links to research tools, data sets and reagents are provided under the following topics:
| Click Here to Find Out More About the Advancing SMA Education and Awareness Program on October 2! |
THE PEDIATRIC NEUROMUSCULAR CLINICAL RESEARCH NETWORK (PNCR)
 | The PNCR is a network of three clinical sites – Columbia University Medical Center (CUMC), Children’s Hospital Boston (CHB), and The Children’s Hospital of Philadelphia (CHOP)– located in the northeastern United States. In addition to these clinics, the data coordinating center for the PNCR is the University of Rochester. The SMA Foundation has been involved in organizing and funding the PNCR Network since its inception and has sponsored the SMA Natural History Study and other PNCR-facilitated clinical research studies. |
The primary objective of the PNCR Network is to assemble a team of SMA clinical experts in the Northeast, and to build and maintain an active relationship with SMA patients through clinical care and research visits in order to prepare for therapeutic clinical trials in SMA. The Network clinics specifically aim to:
- Offer standardized, comprehensive care for patients that will help to achieve the best possible health outcomes and reduce variability in upcoming clinical trials
- PNCR clinics offer patients access to clinicians in a range of specialties involved in medical care for SMA, including: neurology, pediatrics, genetics, psychiatry, pulmonary, nutrition, pediatric nursing, orthotics, respiratory therapy, physical therapy, occupational therapy, orthopedics and neurosurgery
- Integrate clinical research with care to build a patient base and a pool of SMA families interested in participating in clinical research
- Develop an equipment loan closet, making used wheelchairs and other assistive devices – along with technician services to repair and adjust equipment – available to patients and families who need them
- Educate young clinicians and other healthcare professionals about multidisciplinary care aspects of SMA through direct supervision of medical students, residents, and fellows and presentations at professional meetings
- Support patients and families by organizing educational support groups, sponsoring SMA Day meetings for families, creating new educational materials, updating content for clinical research websites, and publishing periodic newsletters
PNCR Network Tissue Repositories
The PNCR Network also has a Molecular Genetics Core at Columbia University that analyzes genetic samples from patients and maintains a database of molecular genetic results. Furthermore, Columbia University has established a biorepository to store a collection of cell lines and tissue samples from patients with SMA. The repository serves to collect, preserve, and distribute tissues to qualified scientific investigators who are interested in the care and treatment of patients with SMA.
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Photo credit: Chris Henderson, PhD, Columbia University Motor Neuron Center |
Outcome Measure Development
The PNCR Network, along with the International Coordinating Committee on SMA Clinical Trials (ICC), has been working to develop and validate new outcome measures for SMA. Outcome measures are tests that can be used to quantitatively demonstrate the effect of a particular treatment or therapeutic intervention. PNCR clinical sites have made important contributions to the development of the following:
BforSMA Study
On March 25, 2010, the SMA Foundation announced the completion of the Biomarkers for SMA, or BforSMA, pilot study, having discovered over 400 candidate biomarkers for SMA. This community effort involved over 120 study subjects and clinical teams at 18 hospitals across the US and Canada (see map below).
The PNCR Network, along with the International Coordinating Committee on SMA Clinical Trials (ICC), has been working to develop and validate new outcome measures for SMA. Outcome measures are tests that can be used to quantitatively demonstrate the effect of a particular treatment or therapeutic intervention. PNCR clinical sites have made important contributions to the development of the following:
- CHOP-INTEND (CHOP)
- MRI, DEXA in SMA (CUMC)
- In-home pulmonary and motor function monitoring (CUMC)
- Gravity Neutral Orthotic design and evaluation for SMA (CUMC)
- Electrical Impedance Myography (EIM) in SMA (CHB)
- If you are interested in learning more about these and other outcome measures for SMA, you may also find the following sites useful:
SMA Natural History Study
The PNCR Network helped to characterize the SMA patient population and increase understanding of the stages of disease progression through their 24-month+ SMA Natural History Study. Results of this study will assist in discovery research and clinical trial planning. Learning more about a disease like SMA through such a study will also enable clinicians to more easily evaluate the effectiveness of a potential therapeutics. While SMA natural history studies have been performed by other groups in the past, conducting one in a setting that offers comprehensive, multidisciplinary care is important, since the level of care that groups of patients receive can impact the natural progression of the disease.
During the Natural History Study, patients were evaluated regularly at one of the clinical sites – every two months for the first six months, every 3 months for the next 6 months, and every 6 months thereafter. Each visit was free of charge for the research participants. Patients underwent a number of evaluations to assess muscle strength, motor function, muscle mass, respiratory function, motor unit number, and quality of life. Results of the Natural History Study are presently being analyzed and links to relevant publications will be posted here as soon as possible.
INTERNATIONAL COORDINATIONG COMMITTEE FOR CLINICAL TRIALS IN SMA (ICC)
The ICC is a volunteer committee composed of stakeholders from the spinal muscular atrophy (SMA) community who have agreed to work together to address the opportunities and challenges associated with effectively organizing clinical trials of potential new treatments for SMA. The SMA Foundation is one of the four main funding organizations of the ICC. The mission of the ICC is to facilitate the conduct of fast, efficient and successful clinical trials in SMA that lead to new treatments, and ultimately improve care for people living with SMA. ICC members work to fulfill the mission, in part, by improving or developing new outcomes measures for SMA. In recent months, members of the ICC have published papers on two new functional measures for SMA, the Six-Minute Walk Test and the CHOP-INTEND .
Other accomplishments of the ICC since its inception in 2004 include the following:
The PNCR Network helped to characterize the SMA patient population and increase understanding of the stages of disease progression through their 24-month+ SMA Natural History Study. Results of this study will assist in discovery research and clinical trial planning. Learning more about a disease like SMA through such a study will also enable clinicians to more easily evaluate the effectiveness of a potential therapeutics. While SMA natural history studies have been performed by other groups in the past, conducting one in a setting that offers comprehensive, multidisciplinary care is important, since the level of care that groups of patients receive can impact the natural progression of the disease.
During the Natural History Study, patients were evaluated regularly at one of the clinical sites – every two months for the first six months, every 3 months for the next 6 months, and every 6 months thereafter. Each visit was free of charge for the research participants. Patients underwent a number of evaluations to assess muscle strength, motor function, muscle mass, respiratory function, motor unit number, and quality of life. Results of the Natural History Study are presently being analyzed and links to relevant publications will be posted here as soon as possible.
INTERNATIONAL COORDINATIONG COMMITTEE FOR CLINICAL TRIALS IN SMA (ICC)
The ICC is a volunteer committee composed of stakeholders from the spinal muscular atrophy (SMA) community who have agreed to work together to address the opportunities and challenges associated with effectively organizing clinical trials of potential new treatments for SMA. The SMA Foundation is one of the four main funding organizations of the ICC. The mission of the ICC is to facilitate the conduct of fast, efficient and successful clinical trials in SMA that lead to new treatments, and ultimately improve care for people living with SMA. ICC members work to fulfill the mission, in part, by improving or developing new outcomes measures for SMA. In recent months, members of the ICC have published papers on two new functional measures for SMA, the Six-Minute Walk Test and the CHOP-INTEND .
Other accomplishments of the ICC since its inception in 2004 include the following:
- Supported publication and dissemination of:
- Consensus Statement on Standard of Care for SMA; 2007, Child Neurol Wang et al. 22 (8): 1027
- Learning to walk: Challenges for spinal muscular atrophy clinical trials , The International Coordinating Committee (ICC) for SMA Subcommittee on SMA Clinical Trial Design, Kaufmann, P. Muntoni, F., 2007 Neuromuscul Disord. 17: 499 – 505
- Advanced reliability studies for various strength and functional outcome measures
- Established an independent Oversight Committee and community funding for the International SMA Registry at Indiana University
- Convened the SMA Summit on Drug Development in Bethesda, MD (September 2007) with over 100 attendees with industry, government, and clinical research arenas
- Achieved NINDS NPTUNE project allocation for SMA
- Supported TREAT-NMD activities in Europe; facilitated dialog regarding harmonization of registry and clinical trial efforts
- Met with European Medicines Agency and Food and Drug Administration on SMA topics
BforSMA Study
On March 25, 2010, the SMA Foundation announced the completion of the Biomarkers for SMA, or BforSMA, pilot study, having discovered over 400 candidate biomarkers for SMA. This community effort involved over 120 study subjects and clinical teams at 18 hospitals across the US and Canada (see map below).
A biomarker is an indicator of a biologic state, disease process or drug response often used in drug development. It can be used to measure normal biological processes, pathological processes relating to an illness, or pharmacologic responses to a treatment or therapeutic. Biomarkers can be directly related to clinical endpoints. The information collected in this study will be used to help identify biomarkers of disease severity for SMA. The information can be useful in designing future SMA clinical studies.
The need to have SMA biomarkers identified for upcoming therapeutic clinical trials motivated the SMA Foundation to initiate the BforSMA Study. The primary study objective was to identify candidate blood and urine biochemical markers that correlate with disease severity as determined by the Modified Hammersmith Functional Motor Scale across a range of Type I, Type II and Type III children with SMA. The study also had several secondary objectives:
- To determine if there are biomarkers from Types I-III SMA patients that correlate with SMA type, age at disease onset, 10-meter Timed Walk Test (ambulatory subjects only), pulmonary function, feeding and nutritional assessments, SMN protein level, SMN transcript level or SMN2 copy number
- To determine if identified candidate biomarkers are associated with the disease state through comparison of SMA specimens with control volunteer specimens
- To determine if there are potential biochemical pathways that may represent targets for therapeutic intervention in SMA
- Children with type I SMA (n=15)
- Children with type II SMA (n=45)
- Children with type III SMA (n=40)
- Unaffected children (n=20) matched the gender and age distribution expected in the SMA cohorts.
The study identified more than 400 candidate biomarkers. The unexpectedly rich list of candidate markers creates the basis for many future studies including the confirmation of a panel of potential markers, a focused look at metabolic questions in SMA patients and the generation of new hypotheses about pathophysiology of SMA. A manuscript for publication is in development. Next steps in confirming and validating these candidate biomarkers are currently being pursued in conjunction with contract research organizations, academic collaborators, and industry partners. The Foundation intends to have a shorter list of plasma protein biomarkers and assays able to measure them by the end of 2010.
The SMA Foundation extends its thanks and appreciation to the patients and families who participated in the BforSMA study.
SMN ELISA
Since SMA is caused by reduced levels in SMN protein, it is believed that disease symptoms could be mitigated by a therapeutic that is able to increase SMN protein production. For years, clinicians and scientists have found it difficult to accurately measure SMN from patient cells. To address this problem, the SMA Foundation developed an ELISA assay able to accurately measure the amount of SMN in leukocytes obtained from patient blood. The Foundation is now working to develop an SMN ELISA kit and make it accessible to the SMA research community.
The SMA Foundation extends its thanks and appreciation to the patients and families who participated in the BforSMA study.
SMN ELISA
Since SMA is caused by reduced levels in SMN protein, it is believed that disease symptoms could be mitigated by a therapeutic that is able to increase SMN protein production. For years, clinicians and scientists have found it difficult to accurately measure SMN from patient cells. To address this problem, the SMA Foundation developed an ELISA assay able to accurately measure the amount of SMN in leukocytes obtained from patient blood. The Foundation is now working to develop an SMN ELISA kit and make it accessible to the SMA research community.
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