New Methods, Funding Propel Neurogenetics

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 aimed at facilitating funding for rare diseases is the R.A.R.E. (Rare Disease Advocacy, Research, and Education) Project's Global Genes Fund. The organization's Web site, which is in development, 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.”

Using Neurogenetics in Practice

Genetic testing can be helpful for diagnosing some neurologic disorders, but a “bewildering” maze of tests is available, Dr. Gropman said. Vendors have put together predetermined 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.

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.

None of the sources contacted for this article had any relevant financial disclosures.

DNA sequencing 'is great for rare diseases or to gain a foothold in a disease that has been hard to understand….'

Source DR. HUENTELMAN

Brain MRI scans of a child with microcephaly, polymicrogyria, and schizencephaly (left) and brain scans of a healthy child (right).

Source Courtesy Dr. Murat Gunel