When Hollywood film producer Gordon Gray and his wife Kristen found out several months ago that their two young daughters had a fatal neurodegenerative disorder called Batten disease, they immediately started calling doctors and other families affected by this extremely rare disease to learn more about it.
"As a mother, it was hard because unfortunately a lot of these families do not have children that are still living and hearing those stories early on was devastating because we do not want that to be our reality," Kristen said.
The couple's daughters, Charlotte, age 4, and Gwenyth, 20 months, were diagnosed with a form of Batten disease called late infantile NCL, which affects children between 2 and 4 years old and causes blindness, loss of muscle coordination and seizures. Children usually die between ages 8 and 12. There are currently no treatments that slow or reverse the progression of any form of the disease.
Charlotte started having difficulty with coordination and remembering words when she was 2½ years old. After nearly two years searching for an explanation, doctors finally learned that she had inherited mutations in one of the genes, called CLN6, that is responsible for Batten disease. Gwenyth carries the same defective copies of the gene as her older sister.
Foundation created to fund research
In an attempt to change their devastating reality, the Grays created the Charlotte and Gwenyth Gray Foundation to raise $12 million to fund research on developing treatments for Batten disease. They are using social media -- Facebook, Instagram and Twitter -- to get the word out. Numerous celebrities, including Rihanna, Mark Wahlberg and Jessica Alba, have picked up the cause and asked for donations through their Facebook pages.
"We need to help to accelerate the research because we are in a race for time," Kristen said.
But how long does it usually take to develop a molecule that might only have been tested in the lab into a treatment? How quickly can research deliver a cure for Batten disease, which afflicts about two to four out of every 100,000 people born in the United States?
In the course of educating themselves about Batten disease, the Gray family started talking with scientists at Sanford Research, a non-profit research organization in South Dakota. The disease is so rare, and attracts so little biomedical research attention, that they could not find experts in their home state of California, Kristen said. There have only been two other families in the United States that were diagnosed with the same form of Batten disease as the Gray's daughters.
One of the research teams at Sanford, led by Jill Weimer, is now working with the Gray family, along with a family in Israel affected by the same form of Batten disease, to search for small molecule drugs that could treat it, at least in cells in a petri dish. Weimer and her colleagues are currently growing cells from the Gray daughters' blood -- even cells grown outside of the body show telltale signs of Batten disease -- and testing panels of synthetic drugs to identify one that might reverse the damage in cells.
"Our hope is that next week, Jill calls us to say it seems to be working and we can go through whatever we need to do to (get this to) our daughters," Kristen said.
Searching for the magic molecule
In reality, there is no way to know how many molecules will have to be tested to find one that has the desired effect, said David Pearce, president of Sanford Research, who has been studying Batten disease for about 15 years. The researchers are, however, choosing molecules wisely based on what they think may be going awry in the disease, including molecules with anti-inflammatory properties.
Once there is a molecule that looks promising, the time it takes to start testing it in clinical trials in people, including possibly the Gray daughters, "could be anywhere from one to five years," Pearce said.
The protracted time frame is due to the fact that researchers would first have to show that the small molecule is effective in treating lab animals, such as mice, with Batten disease. Fortunately, this step could be expedited because mice have already been bred that carry mutations responsible for the same form of the disease as the Gray daughters have. (It can take about a year to make a genetically engineered mouse from scratch.)
Finally, it can take about a year to get approval from the Food and Drug Administration to start testing the drug in clinical trials with people. In this case, a couple of things could work in their favor, Pearce said. In his experience, the FDA has approved trials for rare diseases a bit more quickly, possibly because the agency acknowledges that not many, or no treatments are currently available. In addition, some of the small molecules that Weimer's group is testing are already approved for other diseases, so their safety in humans has been studied, which could speed along new clinical trials.
Another path to experimental drugs
The estimate of one to five years to bring a new drug from experiments in cells to studies in people sounds reasonable, said Peter L. Saltonstall, president and CEO of the National Organization for Rare Disorders (NORD), which represents patients and families with rare diseases. However, it could take even longer than usual to begin a clinical trial on Batten disease because there are so few patients who have the disease, he added.
Another way that patients can get access to experimental drugs faster is to apply through the FDA for compassionate use, Saltonstall said. In this case, patients may be able to start taking a drug as long there is some data showing it is safe in people -- for example, if the molecule was already approved and being used for another disease, and possibly even before clinical trials start.
For other rare diseases, families have started groups, such as Parent Project Muscular Dystrophy, that have been very successful at connecting patients to treatments and clinical research, Saltonstall said. And these organizations were established before the days of social media, which is only going to help, he added.
"The Grays can get a significant leap forward because of the access they have to people who could put money into this kind of initiative," Saltonstall said.
Reaching out through social media
The crowdfunding approach that the Grays have taken -- in their case, asking a large group of people, through social media and other communications, to donate $1 for their foundation -- has taken off in the last several years.
In the case of rare diseases, the fundraisers are often parents of children who are affected, but they can also be the researchers working toward a cure, said Nick Dragojlovic, a postdoctoral fellow at the University of British Columbia Faculty of Pharmaceutical Sciences who studies the role of crowdfunding in drug development. The money raised can either go to basic science research or clinical studies, as in the case of the GoFundMe campaign "Saving Eliza" for a four-year-old girl who has a fatal genetic disease called Sanfilippo Syndrome.
Although crowdfunding campaigns have successfully raised the funds for clinical trials, they have not as yet led to new medications on the market, Dragojlovic said. "This is perhaps not surprising, given the long development timelines in drug development and the fact that crowdfunding for research is a relatively new trend," he added.
The money that the Charlotte and Gwenyth Gray Foundation raises could go to a number of basic science initiatives, Kristen said, including the work at Sanford Research on cell-based experiments as well as a research program in New Zealand studying Batten disease in sheep.
"The money that we raise is not going to help just our children, it will help other families that have CLN6 (mutations), and in the broader scope, Batten disease and other neurological diseases," Kristen said.