By Jonathan Briggs
Michael Boss, Athena Diagnostics vice president of operations says, “you have to go where the discoveries are.” Athena offers more than 80 tests for neurological disorders.
For more than 10 years, Athena Diagnostics, a specialty reference laboratory in Worcester, Mass., has been developing sophisticated, high-quality diagnostic tests for rare neurological diseases. Its dozens of specialized tests help physicians diagnose and characterize conditions such as peripheral neuropathy, epilepsy, dementia, movement disorders, motor neuron disorders, mental retardation, neuromuscular disorders, neurometabolic disorders and paraneoplastic syndrome.
The company was started as Genica Pharmaceuticals in 1989 after Lou Kunkel, Ph.D., of Children’s Hospital in Boston discovered the gene responsible for Duchenne Muscular Dystrophy. Genica offered tests that involved a muscle biopsy and analysis for levels of the protein, ‘dystrophin.’ Now a subsidiary of Elan Corp., of Dublin, Athena Diagnostics offers more than 80 neurological tests.
Today, Athena adds new tests through consultation with clinicians, researchers and patient advocacy groups. It also performs testing on common disorders such as Alzheimer’s disease. “On the whole, we built the business by bringing out and adding tests for fairly rare disorders. You have to go where the discoveries are,” said Michael Boss, vice president of operations.
For example, much of the genetic testing Athena does is for patients with peripheral neuropathy. The most common cause of inherited peripheral neuropathy is a disorder called Charcot-Marie-Tooth (CMT) disease, which affects an estimated 150,000 Americans. Athena introduced the first genetic test for CMT about seven years ago and has continued to add other tests for the disorder since then. Often new tests mean new technology.
“We’re not focused on a single technology,” Boss said. “We do the development ourselves or work with experts to develop whatever technology is appropriate for a neurological test. So we have a range of technologies that it would be quite unusual to find in most labs of our size, or even those considerably larger. For example, we have a viral neutralization assay to identify Multiple Sclerosis patients who have developed antibodies to beta-interferon therapy. The test is based on a cell-culture viral neutralization bioassay that would be very unusual for a clinical lab to run. But we felt it would be important to offer this test.”
Examples of new Athena tests include SCA10 for spinocerebellar ataxia; DRPLA (Dentatorubralpallidoluysian atrophy also known as Haw River Syndrome) a degenerative CNS disorder; CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a genetic test for a form of stroke. A new CV2 auto-antibody test helps identify patients who may have occult malignancies.
For Boss, the most exciting news is that Athena is making its first entrée into an area outside neurology with its PKDx test, a genetic analysis used to diagnose polycystic kidney disease. In April, Athena became the first laboratory to offer direct DNA analysis of the two genes responsible for the majority of autosomal dominant polycystic kidney disease (ADPKD), Boss said. In addition to pioneering the clinical area of kidney disease, the PKD test is a change for Athena in that it addresses one the most common inherited disorders in the United States. An estimated 600,000 people suffer from PKD, but its prevalence did not make developing the test any easier.
Mike Jocson and Jeanette Vanderpoel perform restriction digestion for CMT1A assay.
Although the two genes involved in the disorder were identified years ago, “there were impediments to turning it into a clinical diagnostic test,” Boss said. “Both genes are very large and complex. Certainly PKD1 is the largest gene being analyzed in a clinical diagnostic test. Also, because there are many copies of the PKD1 gene that are very similar, it is difficult to distinguish the active gene from the inactive copies in the human genome.”
There are two forms of APKD. About 85 percent of patients have PKD1 and the rest have PKD2. Developing a reliable DNA test to identify the genes responsible for each type was important because PKD1 is more serious and often leads to the need for renal transplantation.
Athena worked with researchers from John Hopkins University, Albert Einstein College of Medicine and Yale University. PKD testing requires analysis of 61 exons spanning more than 16 kb (16,000 base pairs) of genetic code. A large region on the PKD1 gene is replicated more than four times on the same chromosome. This homologous region renders standard diagnostic techniques ineffective because routine PCR amplification and hybridization detect all replicated regions and not all of them are important.
Unlike other molecular diagnostic assays where mutations cluster in certain easily analyzed gene segments, the mutations in the PKD1 and PKD2 genes occur throughout the gene. There are no hot spots or clusters. To overcome this, Athena uses a combination of technologies. The Athena PKDx test first uses long-range PCRs to sort out the non-functional homologous regions of the PKD1 gene to ensure that only the proper sequence is analyzed.
In addition to diagnosing PKD, the test screens potential kidney donors. PKD causes about 20 percent of all end-stage renal disease. Transplant is the only treatment for ESR patients. Since organs donated by a living relative are most likely to provide a successful transplant and because PKD is a genetic disorder, it is important to know if a potential donor has PKD. Diagnostic methods such as ultrasound do not always provide definitive results. By determining the PKD status of a potential donor, the PKDx test aims to decrease the number of patients waiting for a cadaver kidney.
Facing complexity with education
Educating clinicians is among the most important jobs at Athena. Many neurological disorders have similar clinical presentations and, consequently, are difficult to diagnose. Because so many Athena tests are highly complex, the company strives to educate physicians about its tests and the disorders they diagnose. Toward this end, the company sponsors grand rounds and provides literature and information on the tests, how to use them, and the technologies involved. Information on its Web site (www.athenadiagnostics.com) is supplemented by Internet “Neuro” and “Nephro” casts that update clinicians on developments.
“A few of the tests we do are also done in other labs, but these tests are our specialty. I think we do them particularly well. In every case we work with the leader in the world, and we continually update them. If I or a member of my family needed one of these tests, I would certainly have it done here,” said Boss.
Jonathan Briggs is a freelance writer based in Tijeras, N.M.
