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As enthusiasm for dumping ice on one another fades with autumn and October brings pervasive pink, I wish that attention would turn to families confronting diseases not as well known as ALS and breast cancer.
HOW RARE IS RARE?
According to the National Organization for Rare Disorders, “rare disease” in the U.S. means affecting fewer than 200,000 people. These conditions number about 6,800, collectively affecting nearly 30 million Americans or 1 in 10 people.
Many are single-gene diseases. That means that the chance of more than one family member being affected is quite high (see Mendel's first law). Unlike those, most (>90%) cases of ALS and breast cancer aren’t inherited as single-gene traits, but are sporadic. Mutations happen during a person’s lifetime in somatic cells, perhaps due to an environmental trigger. A family with one member who has ALS wouldn't have as great a chance as it affecting another as a family with Huntington disease, for example.
With so many causes of rare diseases, comparing statistics is an apples-and-oranges exercise. But I collected a few anyway, for prevalence (the percentage of a population with a particular disease at a given time).
Breast cancer (all types) affects 122 in 100,000 people. ALS (all types) affects 3.9 per 100,000. Absolute numbers are more meaningful for the rarest of the rare. For example fewer than 100 people worldwide are known to have giant axonal neuropathy, which is similar to ALS in a young child. But unlike ALS, the chance of a sibling of an affected child also inheriting the condition is 1 in 4.
Thanks to exome sequencing, even "one-of-a-kind" individuals with strange constellations of symptoms that defy shoehorning into known diagnoses are becoming understood. The exome kids are tantalizing to journalists, like the recent New Yorker article "One of a Kind".
But so very many diseases aren't chosen for the New Yorker, or don't have a Lou Gehrig or Joan Lunden materialize.
WHAT DO RARE DISEASE FAMILIES THINK?
I had mixed feelings about the ice bucket challenge (henceforth “IBC”) for ALS, noting how very few people have read my posts about ALS, compared to important posts like how Dan Brown screwed up genetics in his latest bestseller. So I polled the rare disease families I’ve covered at DNA Science about the IBC, and struck a nerve. They share awe at the brilliance of it, joy at how much was raised for ALS, surprise, and a bit of envy.
”People associated with other diseases became really upset, probably because they wished they had thought of it. It took on a life of its own, and then it just abruptly stopped when people became tired of watching endless videos, and that caused a backlash,” said Ilyce Randell, president and co-founder of Canavan Research Illinois. The organization's major fundraiser celebrates son Max's birthday -- he'll turn 17 later this month. I’ve been to two of them. (Canavan prevalence: about 10 in 100,000.)
Laura King Edwards is running races in all 50 states to raise awareness and funds for infantile Batten disease, which has robbed her younger sister Taylor of her sight, mobility, speech, and ability to eat. Laura took the IBC and attempted to extend its reach.
“I did try to post some more educational/advocacy-related links on the Taylor’s Tale Facebook and Twitter pages. Those posts didn’t get much response. People didn’t want information with meat to it - they wanted to watch entertaining videos of their friends. That’s where our challenge comes in - how to identify strategies that are sustainable. Because if I know anything, it’s that the fight against rare disease won’t be won overnight,” she said. (Prevalence of all forms of Batten disease is 2 to 4 of every 100,000).
The IBC seemed to have gotten under the skin, in one way or another, of everyone I contacted.
“We didn't pay much attention to it, and did not accept the challenge from anyone. We kept the focus on our goal,” said Jennifer Pletcher, whose daughter Finley has Leber congenital amaurosis (LCA; visual loss) caused by mutation in the RDH12 gene. “Some people actually did the challenge and donated to our foundation, which was cool,” she added, pointing out that October is Blindness Awareness month. Prevalence of her daughter’s condition: a tenth of the 2-3 per 100,000 who have any of the 22 genetic forms of LCA.
RARE GENETIC DISEASES: TO LUMP OR NOT TO LUMP?
Ilyce Randell echoes Jennifer Pletcher’s focus on her family’s disease. This isn’t being selfish, it’s using genetic logic. While rare disease umbrella organizations are enormously helpful in sharing information and strategies, funding clinical trials is a different challenge.
Testing a treatment for a single-gene disease requires participants who share mutations in the same gene. Finley's LCA is due to mutation in a different gene than the one that is mutant in Corey Haas, the boy at the heart of my book The Forever Fix: Gene Therapy and the Boy Who Saved It.
Campaigning to treat all forms of LCA, or all forms of Batten disease, is useful in addressing shared concerns, but might dilute the financial power in getting a phase 1/2 clinical trial off the ground, or support the daunting cost of a phase 3 trial necessary for FDA approval for marketing.
“Fundraising/awareness campaigns are more effective when we do not try to unite every similar disease. Parents of children affected by Canavan who raise money and direct it to a blanket organization are often times not helping advance research for their own child. We are raising money for the only researcher who has ever worked with living Canavan patients in a clinical setting. But there are families raising money for ’research’ for ‘allied diseases,’ organizations that do not even fund her work. When it comes to curing my son I’m not in a true alliance with any other disease because all funding is scarce, and different diseases are competing for the same federal funds,” shared Ilyce.
And that competition is fierce. Just two days ago, the U.S. Food and Drug Administration (FDA) announced “awards of 15 grants worth more than $19 million to boost the development of medical device, drug, and biological products for patients with rare diseases.” Six are going to cancers, 2 to infectious diseases, 4 to others that aren’t inherited, and of the 3 that are, two are for sickle cell disease and one for cystic fibrosis – classic textbook genetic diseases. “You have an easier time asking for money for something people have heard of,” said Ilyce.
Glenn O’Neill is more enthusiastic than most about the IBC, perhaps because his family’s efforts to “save Eliza” from Sanfilippo syndrome also went viral, before the ice buckets descended . They adapted the “challenge” part of the ice bucket craze.
“On August 12th we started our #Sing2Lines to stop Sanfilippo challenge based on Eliza's love of music and the fact that she can still sing. You post a video of yourself singing 2 lines of any song, and challenge 5 friends, to give Eliza and other children a voice, and a chance at life,” Glenn told me.
They’ve sung their way to more than $75,000 with thousands of entries, including one from actress Andie MacDowell .
PAYING FUNDRAISERS
For the rarest of the rare, the rarest of the rare, fundraising efforts are usually family-run, all volunteer. This is not often the case for more common conditions. When any disease organization calls for a donation, it’s a good idea to ask how much of what you donate actually goes to research or patient support. Or check out Charity Navigator.
A caller for a large breast cancer organization had the misfortune of getting my husband on the phone last October. Larry volunteers for several not-for-profits, and he immediately interrupted the script to ask whether said organization paid the people who made the phone calls. Yes, they did.
“But breast cancer is so common! You must know someone who has it!” insisted the paid caller.
“If it’s so common, why can’t you get volunteers to make the phone calls?”
Laura King Edwards weighed in with “Pink for One Heck of a Price Tag” two years ago, noting that the NFL shelled out $5 million on ads and paraphernalia for their breast cancer awareness blitz. “If I could write a $5 million check to the world’s best Batten disease experts, I believe in my heart that they’d give us a treatment that works,” she wrote.
Others chimed in on the cost of fundraising issue.
“For Finley's Fighers- 100% goes to research. We don't have overhead cost or paid employees. We rely on sponsors for our events and all other costs come out of the family's pockets,” said Jennifer Pletcher.
Kristin Smedley, who has two sons with the CRB1 form of LCA, agrees. “I let my supporters know that our fundraising does not pay salaries, it does not pay for office space, it does not pay for public relations firms to get me on TV. We are all volunteers here working out of our kitchens.” Their annual event, Bike the Basin, raises enough funds to sponsor an annual research meeting – I had the pleasure to attend the first one and the next one is later this month.
I’m not insensitive to the challenges of cancer. I had it. And I watched my mother undergo treatment for metastatic breast cancer. But an entire month of “raising awareness” for breast cancer? Who hasn't heard of it? And who is being ignored as a result?
IN AWE OF JACEY
Of all of the inspiring rare disease family members I’ve “met” during my writing journeys, the most spellbinding is Jacey Mukka. She turns 22 later this month; she didn’t think she’d live past 21.
Jacey has juvenile Huntington disease (JHD). With prevalence 5% that of the adult version of HD, which is only 5.7 cases per 100,000, there isn’t much interest. Clinicaltrials.gov lists only one trial, from the European Huntington’s Disease Network, that tracks kids who have symptoms, rather than still-healthy at-risk individuals who’ve inherited the mutation.
For another apples-to-oranges comparison, I entered “glioma,” the type of brain cancer that’s just received 3 of the 15 grants from FDA, into clinicaltrials.gov: 1,439 hits.
Jacey’s dad and little sister Karli passed away from HD; Jacey’s older sister has it too. Jacey is very ill, but I don’t want to dwell on her body here. Details are in another post. Instead, I’d like to share her thoughts.
“I promised myself when I was younger I would die before my little sister, I would die before my father, I would die if I ever got the temper of my father or started hurting people.” But that didn’t happen. Karli died at age 13, in 2010. Jacey remembers.
“Reality still hadn't hit, until the nurse came in. She said to come say goodbye. No it's not possible, it can't be. I went into her room and I saw her lips were blue. Mom and Erica snuggled up to her and she took her last breath. She was free. It hurt worse then I thought ever possible, just hold her bunny and curl up on the couch and cry until you run out of tears, and cry even after that. We gave Daddy her pink rabbit and he held it as tight as he could, and then he died 2 months later.”
Jacey started jhdkids.com after hearing families talk about having children even though a parent has the HD mutation, because “the child wouldn't get sick until it was older and by then they'd have a cure.” Jacey sends hugs and books to the friends she's made, and raises funds to help them get through life, one day at a time. The website is full of facts, stories, and ideas. And it is vital, if only to a few, because no one’s dumping ice to draw attention to JHD.
I wish the ice bucket challenge had brought more recognition to the hundreds of rare genetic diseases that lie so under-the-radar. Far more lasting than the ICB is Facebook, where I hear daily from my “families.” Facebook connects the individual efforts that are so vital to conquering the single-gene diseases, one at a time.
This post originally appeared at DNA Science.
HOW RARE IS RARE?
According to the National Organization for Rare Disorders, “rare disease” in the U.S. means affecting fewer than 200,000 people. These conditions number about 6,800, collectively affecting nearly 30 million Americans or 1 in 10 people.
Many are single-gene diseases. That means that the chance of more than one family member being affected is quite high (see Mendel's first law). Unlike those, most (>90%) cases of ALS and breast cancer aren’t inherited as single-gene traits, but are sporadic. Mutations happen during a person’s lifetime in somatic cells, perhaps due to an environmental trigger. A family with one member who has ALS wouldn't have as great a chance as it affecting another as a family with Huntington disease, for example.
With so many causes of rare diseases, comparing statistics is an apples-and-oranges exercise. But I collected a few anyway, for prevalence (the percentage of a population with a particular disease at a given time).
Breast cancer (all types) affects 122 in 100,000 people. ALS (all types) affects 3.9 per 100,000. Absolute numbers are more meaningful for the rarest of the rare. For example fewer than 100 people worldwide are known to have giant axonal neuropathy, which is similar to ALS in a young child. But unlike ALS, the chance of a sibling of an affected child also inheriting the condition is 1 in 4.
Thanks to exome sequencing, even "one-of-a-kind" individuals with strange constellations of symptoms that defy shoehorning into known diagnoses are becoming understood. The exome kids are tantalizing to journalists, like the recent New Yorker article "One of a Kind".
But so very many diseases aren't chosen for the New Yorker, or don't have a Lou Gehrig or Joan Lunden materialize.
WHAT DO RARE DISEASE FAMILIES THINK?
I had mixed feelings about the ice bucket challenge (henceforth “IBC”) for ALS, noting how very few people have read my posts about ALS, compared to important posts like how Dan Brown screwed up genetics in his latest bestseller. So I polled the rare disease families I’ve covered at DNA Science about the IBC, and struck a nerve. They share awe at the brilliance of it, joy at how much was raised for ALS, surprise, and a bit of envy.
”People associated with other diseases became really upset, probably because they wished they had thought of it. It took on a life of its own, and then it just abruptly stopped when people became tired of watching endless videos, and that caused a backlash,” said Ilyce Randell, president and co-founder of Canavan Research Illinois. The organization's major fundraiser celebrates son Max's birthday -- he'll turn 17 later this month. I’ve been to two of them. (Canavan prevalence: about 10 in 100,000.)
Laura King Edwards is running races in all 50 states to raise awareness and funds for infantile Batten disease, which has robbed her younger sister Taylor of her sight, mobility, speech, and ability to eat. Laura took the IBC and attempted to extend its reach.
“I did try to post some more educational/advocacy-related links on the Taylor’s Tale Facebook and Twitter pages. Those posts didn’t get much response. People didn’t want information with meat to it - they wanted to watch entertaining videos of their friends. That’s where our challenge comes in - how to identify strategies that are sustainable. Because if I know anything, it’s that the fight against rare disease won’t be won overnight,” she said. (Prevalence of all forms of Batten disease is 2 to 4 of every 100,000).
The IBC seemed to have gotten under the skin, in one way or another, of everyone I contacted.
“We didn't pay much attention to it, and did not accept the challenge from anyone. We kept the focus on our goal,” said Jennifer Pletcher, whose daughter Finley has Leber congenital amaurosis (LCA; visual loss) caused by mutation in the RDH12 gene. “Some people actually did the challenge and donated to our foundation, which was cool,” she added, pointing out that October is Blindness Awareness month. Prevalence of her daughter’s condition: a tenth of the 2-3 per 100,000 who have any of the 22 genetic forms of LCA.
RARE GENETIC DISEASES: TO LUMP OR NOT TO LUMP?
Ilyce Randell echoes Jennifer Pletcher’s focus on her family’s disease. This isn’t being selfish, it’s using genetic logic. While rare disease umbrella organizations are enormously helpful in sharing information and strategies, funding clinical trials is a different challenge.
Testing a treatment for a single-gene disease requires participants who share mutations in the same gene. Finley's LCA is due to mutation in a different gene than the one that is mutant in Corey Haas, the boy at the heart of my book The Forever Fix: Gene Therapy and the Boy Who Saved It.
Campaigning to treat all forms of LCA, or all forms of Batten disease, is useful in addressing shared concerns, but might dilute the financial power in getting a phase 1/2 clinical trial off the ground, or support the daunting cost of a phase 3 trial necessary for FDA approval for marketing.
“Fundraising/awareness campaigns are more effective when we do not try to unite every similar disease. Parents of children affected by Canavan who raise money and direct it to a blanket organization are often times not helping advance research for their own child. We are raising money for the only researcher who has ever worked with living Canavan patients in a clinical setting. But there are families raising money for ’research’ for ‘allied diseases,’ organizations that do not even fund her work. When it comes to curing my son I’m not in a true alliance with any other disease because all funding is scarce, and different diseases are competing for the same federal funds,” shared Ilyce.
And that competition is fierce. Just two days ago, the U.S. Food and Drug Administration (FDA) announced “awards of 15 grants worth more than $19 million to boost the development of medical device, drug, and biological products for patients with rare diseases.” Six are going to cancers, 2 to infectious diseases, 4 to others that aren’t inherited, and of the 3 that are, two are for sickle cell disease and one for cystic fibrosis – classic textbook genetic diseases. “You have an easier time asking for money for something people have heard of,” said Ilyce.
Glenn O’Neill is more enthusiastic than most about the IBC, perhaps because his family’s efforts to “save Eliza” from Sanfilippo syndrome also went viral, before the ice buckets descended . They adapted the “challenge” part of the ice bucket craze.
“On August 12th we started our #Sing2Lines to stop Sanfilippo challenge based on Eliza's love of music and the fact that she can still sing. You post a video of yourself singing 2 lines of any song, and challenge 5 friends, to give Eliza and other children a voice, and a chance at life,” Glenn told me.
They’ve sung their way to more than $75,000 with thousands of entries, including one from actress Andie MacDowell .
PAYING FUNDRAISERS
For the rarest of the rare, the rarest of the rare, fundraising efforts are usually family-run, all volunteer. This is not often the case for more common conditions. When any disease organization calls for a donation, it’s a good idea to ask how much of what you donate actually goes to research or patient support. Or check out Charity Navigator.
A caller for a large breast cancer organization had the misfortune of getting my husband on the phone last October. Larry volunteers for several not-for-profits, and he immediately interrupted the script to ask whether said organization paid the people who made the phone calls. Yes, they did.
“But breast cancer is so common! You must know someone who has it!” insisted the paid caller.
“If it’s so common, why can’t you get volunteers to make the phone calls?”
Laura King Edwards weighed in with “Pink for One Heck of a Price Tag” two years ago, noting that the NFL shelled out $5 million on ads and paraphernalia for their breast cancer awareness blitz. “If I could write a $5 million check to the world’s best Batten disease experts, I believe in my heart that they’d give us a treatment that works,” she wrote.
Others chimed in on the cost of fundraising issue.
“For Finley's Fighers- 100% goes to research. We don't have overhead cost or paid employees. We rely on sponsors for our events and all other costs come out of the family's pockets,” said Jennifer Pletcher.
Kristin Smedley, who has two sons with the CRB1 form of LCA, agrees. “I let my supporters know that our fundraising does not pay salaries, it does not pay for office space, it does not pay for public relations firms to get me on TV. We are all volunteers here working out of our kitchens.” Their annual event, Bike the Basin, raises enough funds to sponsor an annual research meeting – I had the pleasure to attend the first one and the next one is later this month.
I’m not insensitive to the challenges of cancer. I had it. And I watched my mother undergo treatment for metastatic breast cancer. But an entire month of “raising awareness” for breast cancer? Who hasn't heard of it? And who is being ignored as a result?
IN AWE OF JACEY
Of all of the inspiring rare disease family members I’ve “met” during my writing journeys, the most spellbinding is Jacey Mukka. She turns 22 later this month; she didn’t think she’d live past 21.
Jacey has juvenile Huntington disease (JHD). With prevalence 5% that of the adult version of HD, which is only 5.7 cases per 100,000, there isn’t much interest. Clinicaltrials.gov lists only one trial, from the European Huntington’s Disease Network, that tracks kids who have symptoms, rather than still-healthy at-risk individuals who’ve inherited the mutation.
For another apples-to-oranges comparison, I entered “glioma,” the type of brain cancer that’s just received 3 of the 15 grants from FDA, into clinicaltrials.gov: 1,439 hits.
Jacey’s dad and little sister Karli passed away from HD; Jacey’s older sister has it too. Jacey is very ill, but I don’t want to dwell on her body here. Details are in another post. Instead, I’d like to share her thoughts.
“I promised myself when I was younger I would die before my little sister, I would die before my father, I would die if I ever got the temper of my father or started hurting people.” But that didn’t happen. Karli died at age 13, in 2010. Jacey remembers.
“Reality still hadn't hit, until the nurse came in. She said to come say goodbye. No it's not possible, it can't be. I went into her room and I saw her lips were blue. Mom and Erica snuggled up to her and she took her last breath. She was free. It hurt worse then I thought ever possible, just hold her bunny and curl up on the couch and cry until you run out of tears, and cry even after that. We gave Daddy her pink rabbit and he held it as tight as he could, and then he died 2 months later.”
Jacey started jhdkids.com after hearing families talk about having children even though a parent has the HD mutation, because “the child wouldn't get sick until it was older and by then they'd have a cure.” Jacey sends hugs and books to the friends she's made, and raises funds to help them get through life, one day at a time. The website is full of facts, stories, and ideas. And it is vital, if only to a few, because no one’s dumping ice to draw attention to JHD.
I wish the ice bucket challenge had brought more recognition to the hundreds of rare genetic diseases that lie so under-the-radar. Far more lasting than the ICB is Facebook, where I hear daily from my “families.” Facebook connects the individual efforts that are so vital to conquering the single-gene diseases, one at a time.
This post originally appeared at DNA Science.