One of the most unique aspects of the Rare Disease Clinical Research Grants is the mandate to collaborate with a patient advocacy group. “We have noticed that, in order to have a successful research program for rare diseases, we need the involvement of patient advocacy groups. These groups are essential to help with patient recruitment and to act as liaisons between researchers and the group’s constituency of patients and their families,” Dr. Groft said.
In fact, a Coalition of Patient Advocacy Groups has been formed as an arm of the Rare Disease Clinical Research Network.
“The role of advocacy groups has really matured over the last several years,” Dr. Gropman said. “I work closely with an amazing advocacy group in the Urea Cycle Disorders Consortium. They have gone from a grassroots support of families to major partners in research.”
Dr. Gropman credits the group with raising important clinical questions that only those living with affected individuals might be aware of, educating patients and their families about the importance of participation in clinical trials, as well providing financial support and finding philanthropic partners.
“Patient advocates have a vested interest in moving the clinical research process along,” she said.
Another new initiative to facilitate funding for rare diseases is the R.A.R.E. (Rare Disease Advocacy, Research, and Education) Project’s Global Genes Fund, a Web site in development that aims to serve as a clearinghouse for rare disease philanthropy.
“As long as the rare disease community works in their separate disease silos, we can only get so far. ... If we can bring the community together and not focus on an individual disease, we can create a unifying campaign and rare diseases then becomes a huge public health issue, larger than the U.S. AIDS community and equal to that of breast cancer,” said Nicole Boice, founder and president of R.A.R.E.
One part of the Global Genes Fund, which is set to launch in the second quarter of 2011, will showcase innovative scientific research projects that individuals or businesses can contribute to, in donations as small as $25. Initially, Ms. Boice expects to focus on 10-20 research projects.
“As the platform grows and is successful at securing funding, this will catalyze this type of innovative funding,” she said.
Using Neurogenetics in Practice
Genetic testing can be helpful for diagnosing some neurologic disorders, but there is a “bewildering” maze of tests available, Dr. Gropman said. Vendors have put together pre-determined panels for whole exome sequencing of some disorders, such as spinal cerebellar ataxia or disorders associated with mental disabilities.
“Using a panel, you can test for a number of different genes simultaneously, but you cannot separate them,” she said.
Also coming to market are “designer” panels that allow clinicians to pick and choose which genes to target, but they require knowing a priori which mutation to focus on.
“While the technology has exploded, knowing which test to order can be baffling for many clinicians who do not have extensive backgrounds in genetics. If we find a variant but don’t know its significance, it opens up a diagnostic conundrum,” Dr. Gropman said. The field is still in flux, so many other questions must be resolved, such as how to deal with difficult or unanticipated results and whether technology and interpretation need to be standardized.
Genotyping is not just a black-and-white issue, according to Dr. Huentelman. In addition to the knowledge of a patient’s mutation status, genotyping results must also take into consideration the risk of developing clinical symptoms and the ethical and pragmatic issues that knowledge raises for patients and physicians.
As a first step, neurologists should begin educating themselves about the new technologies, potential applications, and shortcomings, by attending sessions on neurogenetics at annual professional meetings or more specialized conferences. While commercial vendors may provide varying degrees of advice about test selection, creating a professional relationship with a geneticist or genetic counselor might provide access to the most up-to-date information and options.
“You need someone fully entrenched in the field of human genetics,” said Dr. Huentelman, who advocates creating a genetics team to sort through the maze of data that can be generated by a genetic analysis.
As a specialist in translational medicine, Dr. Huentelman focuses on understanding the genetic cause of disease and then translating this information into new diagnostic tests and therapeutics. While new DNA sequencing methods are quickly making the first goal a reality, accomplishing the second goal still remains “hopes and dreams,” he said. The ultimate goal of genetic mapping is to personalize medicine by shifting clinical practice from that based on clinical symptoms to that tailored to an individual’s genetic make-up, but broad gaps in knowledge remain. The hope is to develop pharmaceuticals to correct the deficiency caused by a particular mutation or to use genetic testing to preselect patients who might benefit from a particular therapy, similar to the ongoing work on apolipoprotein E genotype status and Alzheimer’s disease.