Challenges abound as researchers search for rare disease treatments


Doctors may go years without seeing a rare disease -- also known as an orphan disease -- but they affect 30 million Americans.

There are about 7,000 diverse diseases classified as rare in America alone, which according to the United States Government, means that less than 200,000 individuals have this particular disorder at one given time. On Feb. 28, advocates are putting the spotlight on rare diseases during Rare Disease Day and promoting the message of "Rare Disorders without Borders," to aid in the international effort to work together to battle these conditions.

The U.S. currently has more than 420 medications approved to treat various rare diseases. While legislation has provided incentives to encourage pharmaceutical companies and sponsors to research rare diseases, much stands in the way of finding cures for these illnesses.

Motivating research

Today, about 20 medications are approved to treat rare diseases annually, and about one-third of brand new drugs the agency approves are for these uncommon conditions, Anne Pariser, associate director for rare diseases at the Food and Drug Administration, told Last year, 13 brand new drugs were approved for 14 different indications and an additional 12 existing medications were approved to treat various rare diseases.

"There's an aggressive push over rare disease research, and researchers have much more tools in their toolbox," Michael Kelly, the chief scientific officer of Cure Duchenne, said to Kelly was a former pharmaceutical executive who served as president and U.S. site head for Renovis, Inc. and held senior positions at Amgen, Wyeth (Pfizer) and Wellcome (GlaxoSmithKline).

"We've also seen both large pharmaceuticals and small get interested. The pharmaceutical industry has changed in the last few years, and orphan diseases have become an important part of their portfolio," he added.

There's more at stake than saving these patients: Looking into these uncommon diseases has already been shown to create a pathway for treating and curing some of our most prevalent ailments.

For example, Nobel Prize-winning research about a rare, genetic condition has lead to groundbreaking information about how to fight high cholesterol. Michael Brown and Joseph Goldstein were researching familial hypercholesterolemia -- an inherited condition that causes high levels of low density lipoprotein (LDL) cholesterol from birth -- when they won the Nobel Prize in Physiology or Medicine in 1985. They discovered that 20 percent of all heart attack survivors had one of three single gene-determined types of inherited high cholesterol disease, and one heterozygous form of familial hypercholesterolemia (meaning only one of the inherited genes was mutated) was found in 1 out of every 25 heart attack victims.

Through their research, they were able to discover a pathway of how cholesterol is absorbed in the cells, providing invaluable information for anyone who is battling high cholesterol, Dr. William Gahl, clinical director of the National Human Genome Research Institute (NHGIRI) and director of the National Institutes of Health's Undiagnosed Disease Program, told

The U.S. recognized the potential rare disease research could have on other illnesses, and Congress approved the Orphan Drug Act in 1983. The legislation states that if an organization can prove through animal models and clinical data that a particular drug is promising for a specific rare disease, it can receive tax credits toward future clinical trials. This includes the ability to write-off some of the research and development (RND) costs. It also includes a waiver for fees associated with submitting a medication to the FDA for marketing approval, which can average $1.9 million per drug.

One of the most lucrative parts of the act for pharmaceutical companies is that if their medication is approved, they get seven years of market exclusivity. No other drug can go to market for that disease, unless it is proven that a newer, not similar, medication is better at treating the disease.

In the decade before the act, only 10 medications were approved to treat rare diseases. Today, the FDA currently receives about 300 requests a year for developmental medications to be designated for rare diseases, and about 70 percent receive that approval, the agency aid.

In addition, a number of patient advocacy groups for rare disorders petitioned Congress to fund the Rare Disease Clinical Research Network in 2003. Ten million dollars was given to the NIH Office of Rare Diseases Research to establish a network of scientists who were researching various illnesses.

Prior, there had always been a struggle to find enough rare disease patients in one area for a clinical trial because the incidence rate was so low. Now, companies could just tap into a database of hundreds of patients who have full histories and have been placed on the same protocols, ready to enter clinical trials.

"Drug companies have been historically less interested in investing money to develop drugs because of the expense of doing that and the return on patients," Dr. Mark Batshaw, the chief academic officer for Children's National Medical Center and the professor and chair of the department of pediatrics at The George Washington University School of Medicine and Health Services, which are both in Washington, told "With the Orphan Drug Act and the Rare Disease Clinical Research Network, drug companies are now looking at the global market rather than just the U.S. market."

Batshaw's group was among the first 10 research centers funded through the initiative. His research focuses on urea cycle disorders.

When people usually eat protein, it is broken down into amino acids, which help form hormones that maintain the body's well-being. Components that are not required, like nitrogen and ammonia, are metabolized with enzymes primarily in the liver and released through the urine. Someone who has a urea cycle disorder, however, has an enzyme defect that causes ammonia to accumulate in the body. It becomes very toxic to the brains of young children and can cause death.

Through the funding, Batshaw was able to pool together 15 sites that were studying urea cycle disorders, including 12 in the U.S., one in Canada and two in Europe. Before the consortium was formed, the largest study involved 23 patients. Now, they have over 600 patients representing 20 percent of all the people identified with urea cycle disorders.

"You can cut down the cost of getting a drug to market for a rare disorder if you have a consortium that includes many sites," Batshaw explained. "If you have a large enough number of individuals to perform the study and if all those individuals are following a single clinical guideline and followed longitudinally over a period of time, it cuts costs enormously."