Clinical Research

Our Clinical Research

The mission of the SMA Foundation is to accelerate the development of a treatment for SMA. The SMA Foundation works to accomplish this mission, in part, by funding clinical research. We are enthusiastic about the recent progress that has been made in drug discovery for SMA and are working to prepare for imminent clinical trials for potential SMA therapeutics.

Our Clinical Research page contains the following sections:

• Information for the newly diagnosed

• What you should know about participating in clinical trials

• What clinical trials are available or approching for SMA?

• Clinical research projects of the SMA Foundation

• Pediatric Neuromuscular Clinical Research Network (PNCR)

• SMA Natural History Study

• SMA Biomarkers Study

• BforSMA Study
• SMN ELISA

• International Coordinating Committee for Clinical Trials in SMA (ICC)

INFORMATION FOR THE NEWLY DIAGNOSED

• Our website has several resources that newly diagnosed patients and their families may find helpful.Our Frequently Asked Questions page includes information on the genetics of SMA, the spectrum of disease severity, the SMN2 gene and its importance in the development of treatments for SMA, and other general information about the disease and links to relevant websites.

• The Family Guide to the Consensus Statement on the Standard of Care for Spinal Muscular Atrophy outlines current expert opinion on the standard of care for people living with SMA and enables patients to be proactive about obtaining the level of SMA-specific care they need or want.

• SMA Overview: An Introduction for SMA Families and other presentations designed by the SMA Foundation to help families better understand the science of SMA and some of the therapeutic strategies currently under development.

• Our glossary of SMA terminology may also be of assistance to patients and families navigating our website as well as the scientific and clinical literature on SMA.

• Additional resources for the newly diagnosed:

• Other SMA Organizations

• Families of SMA
• Fight SMA
• MDA

• Clinical Trials Listing

• Clinicaltrials.gov

• Clinical Information

• Breathing Basics: Respiratory Care for Children with SMA from Families of SMA
• Caring Choices: For Parents of Infants Newly Diagnosed with SMA Type 1 from Families of SMA

• Pediatric Neuromuscular Clinical Research Network

• Columbia University Medical Center SMA Clinic
• The Children’s Hospital of Philadelphia Neuromuscular Program
• Children’s Hospital Boston SMA Clinic

WHAT YOU SHOULD KNOW ABOUT PARTICIPATING IN CLINICAL TRIALS

What does the process of developing a new medical treatment entail?

The medical research process begins with a basic investigation of how a therapeutic intervention (drug or other treatment) might work for a particular disease. Early on, the intervention may be tested in human cells and/or animals. Studies are carried out by researchers in academic or industry labs and are published in peer-reviewed journals.
	After studies in cells and animals provide sufficient evidence that a particular intervention is likely to be a safe and effective treatment for a disease, the company or organization developing the therapeutic intervention files an application with the Food and Drug Administration (FDA) to obtain permission to begin testing in human subjects though a clinical trial.

What is a clinical trial?
Clinical trials are studies conducted using human participants and designed to explore and answer questions related to a disease and to examine potential new therapies. Clinical trials that examine potential new therapies are generally categorized into a series of carefully designed phases:

• Phase I trials – initial studies to determine the safety and pharmacologic actions of drugs in humans, and the side effects associated with increasing doses; in some cases can also be used to gain early evidence of effectiveness.  Healthy participants and/or patients may be recruited for this phase of clinical trials.

• Phase III trials – expanded trials which take place after preliminary data from Phases I and II suggesting drug effectiveness has been obtained and are intended to gather additional information to evaluate the overall benefit-risk relationship of the drug.  After Phase III is completed, a New Drug Application (NDA) or Biologic License Application (BLA) can be submitted to the FDA for approval of the drug for marketing. 

How can I find out more about pediatric clinical trials?
For general information about pediatric clinical trials, the National Institutes of Health has created a family-friendly website, “Children & Clinical Studies”. The site presents interviews with children, parents and physicians who have worked together on clinical trials. Questions addressed include: Will my child benefit from the study? What if I want to say no? What happens when the study ends? 

Why are clinical trials important?
Carefully conducted clinical trials are the most efficient and safest way to determine whether a treatment works in patients and learn more about how to improve health. 

Why participate in a clinical trial?
Patients who participate in clinical trials have an active role in their medical care and a chance accessing potential treatments. Patients enrolled in clinical trials also make an important contribution to the field of medicine, since information learned from clinical trial participants can be used to help others.

How can patients participate in clinical trials?
As a patient or a parent the decision to participate in a clinical trial should be thoroughly evaluated. For more information about clinical trials, including a more complete explanation of what they are, questions to consider and ask before participating in a trial, and information about studies involving a specific disease, please visit http://www.clinicaltrials.gov/ and http://www.ciscrp.org/. Clinicaltrials.gov was developed by the National Library of Medicine and is a service of the National Institute of Health (NIH). The Center for Information & Study on Clinical Research Participation (CISCRP) is a non-profit organization focused on educating and informing the public about clinical research participation.

What clinical trials are available or approching for SMA?

Please visit the clinical trials website and search for ‘spinal muscular atrophy’ in the ‘Search for Clinical Trials’ search engine to find more information about enrolling or ongoing clinical trials in SMA.

In addition, the following SMA clinical trials networks may be able to provide additional information about upcoming trials and how you can enroll.
 
Clinical Trial Networks in the United States:

• AmSMART 
• PNCR Network 
• Project Cure

Clinical Trial Networks in Europe:

• Treat-NMD

CLINICAL RESEARCH PROJECTS OF THE SMA FOUNDADTION

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 Network is the University of Rochester.  The SMA Foundation has been involved in organizing and funding the PNCR since its inception and has sponsored the SMA Natural History Study and other PNCR-facilitated clinical research studies.

Goals of the PNCR

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 in need 
• 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

By preparing these clinical sites for therapeutic clinical trials, the PNCR aims for maximal efficiency in clinical trial recruitment and conduct, enabling rapid evaluation of new potential SMA therapeutics.

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.

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:

• Expanded Hammersmith Functional Motor Scale
• CHOP-INTEND
• 6-Minute Walk Test protocol for ambulatory SMA patients
• MRI, DEXA in SMA
• In-home pulmonary and motor function monitoring
• Gravity Neutral Orthotic design and evaluation for SMA
• Electrical Impedance Myography (EIM) in SMA

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.

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.

SMA BIOMARKER STUDY

BforSMA Study

On March 25, 2010, the SMA Foundation announced the completion of the Pilot Study for Biomarkers for SMA, or BforSMA Study, which 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 be measure normal biological processes, pathological processes relating to an illness, or pharmacologic responses to a treatment or therapeutic. The information collected in the BforSMA study can be used to help identify biomarkers of disease severity for SMA and can potentially be used in future clinical trials.

• 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 the disease is caused by a deficiency in SMN protein, it is thought that disease symptoms could be mitigated by a therapeutic that is able to increase SMN 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.

INTERNATIONAL COORDINATING COMMITTEE FOR CLINICAL TRAILS IN SMA (ICC)

The ICC is a volunteer committee composed of stakeholders from the spinal muscular atrophy (SMA) community – patients, families, advocates, physicians and other caregivers – 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 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 addition, the Standard of Care Subcommittee of the ICC researched and developed a set of guidelines for patient care. This project resulted in publication of the Consensus Statement on Standard of Care for SMA  in Child Neurology and was followed up by the development and publication of the Family Guide to the Consensus Statement.