The objective of these educational materials is to prepare you for what could be one of the biggest decisions of your, or your child’s, life - whether to enroll in a clinical study of an investigational drug or gene therapy. Please click on the icons below to learn more information.
We hope you find resources here to help you make the best decision for yourself or for your child. Please email
The list on the right column of this page (at bottom on a narrow device) includes the active & enrolling clinical studies.
Gene Therapy Educational Materials
The lessons below were developed in collaboration with Salem Oaks. Each lesson will open in a new tab in the Salem Oaks website.We recommend that you view the lessons in sequence. The information builds on each lesson and subsequent lessons refer to information in previous lessons. You will need to set up an account in the Salem Oaks website when you view the first lesson. There is no charge to engage in the gene therapy education. Please send any questions to
Sets the stage with some fundamentals about small molecule drugs and gene therapy approaches to treating Friedreich’s ataxia.
Compares the general risks and benefits of drug and gene therapy clinical studies.
A video of parents receiving the unexpected diagnose of Duchenne Muscular Dystrophy for their son and being presented with the option of enrolling him in a gene therapy clinical trial.
Presents the key concepts of the informed consent process for a gene therapy clinical trial.
Presents tools for how to work through your decision-making to arrive at the course of action that is best for you or for your child regarding gene therapy clinical trial participation.
Basics of Drug Development
You, your child or someone else you love has Friedreich's ataxia. Maybe you found out a year ago, maybe five, maybe you found out yesterday. Most likely by now you've read everything you could possibly read on the subject.
Or, possibly, you are still frantically researching. Despite the significant progress that has been made on the road to finding answers and solutions for FA, there still is no silver bullet, no “get out of jail free” card. And this is an incredibly vibrant and passionate research community, committed to finding treatments and ultimately a cure. So what's the hold-up? Why is it taking so long?
For any disease, whether cancer, muscular dystrophy or Friedreich's ataxia, there are phases of research that scientists must go through to understand a disease and discover potential treatments, as well as a series of steps before a drug or treatment can be prescribed to a patient. In this journey, the number one priority is to ensure patient safety. To be successful, each phase or step demands significant resources—financial, human and organizational. And the highest levels of scrutiny are required in order to ensure a safe and effective outcome. These activities must be done carefully, methodically, usually with several being done at the same time as scientists explore multiple treatment avenues. They explore drugs to slow or stop the underlying disease as well as drugs or interventions to reverse the disease. Additionally, a disease such as Friedreich's ataxia could benefit from the use of different drugs, each addressing specific aspects of the disease. If different drugs are used together, you might hear this referred to as the “cocktail” approach or the combined therapy approach.
Section contributed by Kristi Wright in collaboration with FARA. Kristi is the author of The Basker Twins in the 31st Century. 75% of all royalties from this novel are donated to FA research.
+ What We Understand
Fortunately, scientists have pretty much nailed down the cause for Friedreich's ataxia. Since 1863, when the condition first was described by physician Nicholas Friedreich, scientists have learned a great deal about Friedreich's ataxia. In 1996, they identified the gene responsible for the disease; they've cloned it and decoded its sequence; they've looked hard at the protein the gene produces and the function of that protein. Because of basic research conducted, researchers now know a lot about the causes of FA:
- Both parents have to be carriers of the mutated gene in order for a child to inherit the disease (recessive inheritance).
- The protein frataxin (previously unknown) is severely decreased in FAers (because of the gene mutation).
- Frataxin functions in a specific part of the cell called the mitochondria—the part of the cell responsible for energy production. Many individuals with FA will confirm that they have decreased energy and that they fatigue easily.
- Part of frataxin's job in the mitochondria involves iron and the formation of iron-sulfur clusters that are critical to the energy production process. Some scientists have found abnormally high levels of iron in the mitochondria of heart tissue and parts of the brain in people with FA.
- With much less frataxin protein around to do its job with iron handling and the formation of iron-sulfur clusters, the mitochondria of FAers produce far less energy and far more “free radicals” otherwise known as “oxidative stress” which can damage the mitochondria and eventually even kill the cell.
All of this knowledge is crucial in helping scientists come up with theories about how to treat or possibly cure the disease.
+ Developing the Research Questions
Once the cause is identified, then scientists can develop research questions or possible explanations (hypotheses) regarding potential treatments or even a cure. Current research questions for FA are aimed at:
- How to raise frataxin levels, by adding frataxin or by manipulating the gene
- How to lower iron levels in the mitochondria
- How to decrease “oxidative stress” and/or increase mitochondrial energy production
Scientists first test hypotheses using FA tissue and cells in laboratory test equipment, and when they have a discovery, this is incredibly exciting. However, a major breakthrough in research does not immediately translate into a treatment for a patient. Instead, it triggers a whole set of next steps to test the discovery and its application for humans. Some discoveries won't translate to treatments, but this is not a loss. With every discovery, important knowledge is gained about the disease and often new discoveries move forward faster due to such research.
Of course, the research community needs funding to move forward with both the scientific research necessary to develop the right research questions as well as perform experiments to test against hypotheses. That's one of the reasons why even though there may be countless research questions, they aren't all tested at the same time or at the same speed. Every opportunity takes time, money and resources.
+ Drug Discovery & Development
FARA currently supports a type of basic research called high-throughput screening where scientists develop laboratory-based cell models for screening lots of compounds (hundreds of thousands of compounds) to identify “hits.” For example, one model screens compounds to find drugs that can improve the energy production problem in FA. Usually, this type of screening leads to many hits (a hundred or more.) Then scientists narrow them through more focused experiments. The end goal is to have a few potential drug targets that advance to the next phase of research which, often, is testing in FA specific cell and animal models.
With animal model testing, of course, the better the animal model, the better the test. Scientists have developed FA models in mice, worms and flies, for example. Some of these animals have frataxin protein deficiencies that cause the neurological symptoms of FA, while others have the cardiological symptoms. Still others have genetic mutations on the FA gene that are almost identical to the human mutations so they are excellent models for testing drugs that might be able to address the gene mutation itself.
Several illustrations of this approach are currently available in FA research. In one such case, scientists are treating FA mice – the ones that have genetic mutations very similar to human FA patients – with HDAC inhibitors (Histone Deacetylase inhibitors) which appear to increase frataxin protein levels significantly. In addition to monitoring what happens to the frataxin levels, scientists are looking for improvements in the FA mice and any adverse events or side-effects of the drug. In another case, scientists are making synthetic frataxin protein and attempting to deliver it to the right places in the cells of the FA mice that have neurological symptoms and those that have cardiological symptoms. These scientists, too, are looking for evidence of benefit and any sign of adverse effect.
These animal model screening tests are not always used but can be very helpful in selecting the very best drug candidates with which to proceed to the next step in drug development – safety testing in healthy animals.
Developing new drugs is very tricky. Most of the initial drugs that are found at the discovery phase don't make it to humans because drugs need to pass certain tests. For example, the performance of some drugs will decrease after introduction into humans because they are poorly compatible with our internal environment. Other drugs, while tolerated in cell models and some animal models, may be very hazardous to humans and cause great harm. To maximize the results of the initial discovery drug, researchers work with specialized scientists, called medicinal chemists, to create or identify a variety of related drugs that are similar to the discovery drug, but differ slightly in their chemical nature and structure. Then they test the series of drugs in cell models, animal models and healthy animals. The goal at this point is to maximize the likelihood of success early and to find a lead candidate drug that works best with the fewest side-effects.
+ Safety Testing
Safety testing in healthy animals is required by the FDA in order to show that the drug is unlikely to be hazardous to humans. This is federal law. This testing is usually required in two species of animals (for example, dogs and rats). The testing questions are: 1) How does the animal's body process the drug (absorb, distribute, metabolize, and excrete it), and 2) Do the animals show any signs of toxicology (adverse side effects) and, if so, at how high a dose?+ Drug Formulation & Quality Control
One critical decision is how the drug will be taken by the patient. Is this going to be a pill, and if so will it be chewable or a capsule or a gel tab or some other form? Will it be injectible? Or a patch? These important decisions are based on the chemical properties of the drug and how it is best absorbed by the body and metabolized.
The drug must be produced according to regulatory guidelines related to production that ensure purity and safety. Let's assume a pharmaceutical company has received grants to produce a new drug in large enough quantities to proceed with clinical trials. It's critical that the new drug be produced with the highest of quality control measures. Manual inspection of the drug must be replaced with a more automated approach. There are a series of regulatory guidelines that include safety tests and measures to ensure that when you manufacture the drug it is the same from batch to batch with no impurities. The FDA has published standards for testing new drugs and these standards need to be adhered to via a series of tests. Later the test results are presented to the FDA to demonstrate that the drug has been adequately tested before human trials are proposed.
+ Putting Together a Clinical Trials Team
Finally, researchers are ready to move into human trials which begin with Phase I clinical trials for a new drug. Or maybe a drug has made it through Phase I and is on to Phase II, III, or IV. Each clinical trial requires a team of scientists, organizations (pharmaceutical companies, research organizations, universities, etc.) and patients to get the job done. And from those various organizations there are researchers, study doctors, study registered nurses (RNs) and nurse practitioners, trial coordinators, study pharmacists, data managers, statisticians, and data and safety monitors. These key players must collaborate and have access to the appropriate level of funding to ensure a successful clinical trial.
+ The Clinical Trial
The collaborative team works together to identify the research question to be answered by a particular trial—i.e. what do we want to learn from giving this drug to FA patients? For instance, with the Phase I clinical trial, the primary questions were about dosage and safety: “What's the highest amount of the drug that can be taken without harmful side effects in children, teenagers, and adults with Friedreich's ataxia?” The researchers use all of the data and findings from earlier lab steps to set up the study.
Dosing is never random and testing is always thorough. Once the correct dose is determined in the Phase I trial, a Phase II trial further examines safety and can begin to ask how effective this drug is in a larger group of FA patients at a particular dose. If Phase II results prove statistically significant, a Phase III trial is undertaken. Phase III trials compare the new treatment against the standard of care, or a placebo if no standard of care exists. Essentially, the standard of care is the best proven treatment course available. Patients are randomly assigned to get the new treatment or the standard/ placebo, and these groups are compared against one another. If the comparison shows that the new treatment is safe and has good results, an application will be filed with the FDA to approve the drug. Phase IV clinical trials are sometimes conducted after the drug is approved for sale and are also called Post Marketing Surveillance Trials. They may be required by the FDA or conducted by the drug company. Two examples of Phase IV clinical trials include looking at possible problems in taking the drug with other drugs, and exploring the use of the drug in populations that were not eligible for earlier phases of the clinical trial.
Each phase requires more resources, more organizations involved, and typically it takes longer to complete each additional phase.
+ Importance of Good Trial Design
It is critical that the clinical trial be set up for success. These are very expensive and time consuming endeavors and nearly impossible to recreate. They are emotional for the patients and their families. The last thing anyone wants is to rush through the set up and end up with a clinical trial that doesn't move Friedreich's ataxia research forward. A crucial activity is the design of how the trial will be conducted as well as the primary questions and measures to be monitored. Questions that must be considered include:
- How old should the FA patient be?
- What types of tests will adequately answer the research question?
- Do we have quantitative tests and measures that will demonstrate statistically significant improvement?
The trial plans must be written up so that they can be reviewed and approved by internal review committees and the FDA. These reviews are intended to ensure patient safety and trial appropriateness. Finally, it's critical that staff be trained on the accurate implementation of the trial and the recording of data. The FDA verifies that you have targeted sound laboratory data and quality control is complete. Institutional committees such as a research committee double-check that the hypothesis is based on good science. The Institutional Review Board checks that the study ensures patient safety and that it is accurately and thoroughly explained in the informed consent.
+ Measuring the Results
Every disease requires natural history data and consistent measures to ensure that clinical studies move the research forward. FARA and MDA have invested significant money and resources to ensure that FA has a strong database that documents the clinical symptoms and progression of FA and evaluates specific tests or measures, such as a neurological scale, timed walk, speech, vision, and quality of life measures.
For FA, outcome measures include a 9-Hole Peg Test (9HPT), timed 25-Foot Walk (T25FW), Low-Contrast Letter Acuity test (LCLA), International Cooperative Ataxia Rating Scale (ICARS), and Friedreich's Ataxia Rating Scale (FARS).
Work continues on metrics and biomarkers. Researchers continue to look for quantifiable ways to measure the status of a person's FA as accurately and precisely as possible. When a clinical trial asks if a drug is making a patient's FA better, there must be a way to measure this quantitatively. In addition to the functional rating scales, there are significant research initiatives to find good biomarkers for FA. A biomarker is usually a blood or urine test that correlates with whether the disease is getting better, getting worse, or staying the same. Biomarkers are important because they are unbiased, quantitative ways to measure disease and the effectiveness of treatments. Good biomarkers allow scientists to decide more efficiently which drugs are most promising to advance to later phases of clinical trials.
+ Key Partnerships
Through all these stages, partnerships are essential—partnership with a pharmaceutical company or drug development company is required to optimize development of a new drug and produce the drug in sufficient quantities so that clinical tests with humans can proceed. Organizations, such as FARA, offer grants to companies in order to facilitate the drug development process. Some of the pharmaceutical companies we work with are smaller companies with fewer resources available to them. They can develop the drug to a certain point, but they need help with funding the drug development for a specific compound and to develop FA therapeutics. For instance, FARA and the MDA have given grants to the basic scientists who discovered HDAC inhibitors for FA and to Repligen (a pharmaceutical company) that did the early development work for HDAC inhibitors in FA. Also, FARA and the National Institutes of Health (NIH) have provided support to Edison Pharmaceuticals for the development of drugs that improve mitochondrial function.
Each of the organizations involved provide important expertise. The discovery scientist has very specialized knowledge that leads to the identification of good candidates for drugs, but he or she may not have the expertise required to take a candidate and potentially turn it into a drug that the FDA might approve. The pharmaceutical company is perfectly honed to develop drugs but may lack expertise in a particular disease, especially a rare disease like Friedreich's ataxia. And the pharmaceutical company also needs help in gaining access to the patient community.
FARA participates in these critical partnerships at multiple levels, by providing:
- Financial resources
- Access and representation to the patient community (for example, the FARA Patient Registry)
- The linking between the researchers and the pharmaceutical companies
- The critical infrastructure required for clinical research (Patient Registry, ataxia scales and clinical measures, Collaborative Clinical Research Network of FA centers, etc.)
- Advocacy for Friedreich's ataxia—the motivation and drive to keep researchers, larger funders such as the NIH, and companies moving as quickly as possible
- Representation of the patient community in meetings with the regulatory agencies
- General advocacy for orphan diseases
