rare disease

At the beginning of the year, we were all holding our breath for the future of PacBio. And by all, I mean all. It seems everyone has been rooting for this sequencing technology company.

And why? It’s simple. Pretty much everyone is in agreement that they have the highest quality reads on the market.

So why was their future in question? This could have been asked of many famous companies at one time or another. Apple computer faced their dark days. Disney overcame initial failure. A company’s success in the market does not always align perfectly with the quality of their product. There are other variables.

PacBio at the end of this year is a different company. They have raised two rounds of financing. They have released their Sequel IIe, and they have a new CEO, Christian Henry. From August to November, their stock tripled in price. So what happened? And what is Christian’s new vision for the company?

The main takeaway today is that Christian believes in PacBio’s existing core story: long reads will take science, medicine, and the world to new heights. He thinks this story has been undersold and plans to change that.

There’s an urgency about Stephen Kingsmore. Which is not to say he’s in a rush.

He’s the CEO of the Rady’s Children’s Genomics Institute. He and his team have two world records to their name for the incredible speed of diagnosing a rare disease using whole genome sequencing. The latest is 19.5 hours.

Dr. Kingsmore feels they can even shave time off that. They’re shooting for a new record of somewhere around 12 hours.

"Seriously ill babies don’t have time. They need tests now. Why should whole genome sequencing be different than any other diagnostic test? This is not for intellectual purposes." Says Stephen on today's program.

We’ve heard arguments for whole genome sequencing becoming standard of care before on Mendelspod, but none with this clarity or urgency. The bottom line is this: whole genome sequencing is already standard of care at Rady Children’s, says Stephen, but with an asterisk. The costs are still high, and the team still has work to do to make the argument to payers.

The sequencing center serves hospitals in all four counties of Southern California and is building partnerships around the country. Dr. Kingsmore predicts they will be a model for children's hospitals nationwide.

Mary Norton is a perinatologist and clinical geneticist at UCSF who says that in the age when we are diagnosing ever more rare diseases, adding to the carrier screening panel can be a good thing, but it’s complicated.

But it can be a good thing.

But it’s complicated.

Traditionally carrier screening was limited to ethnic groups, Mary tells us at the beginning of today’s interview, but has now been expanded to what’s called universal screening. The question for OB/Gyns like her is calling the limits on the panel. And it’s not just docs, labs or scientists who are savvy as to the latest conditions studied. Today’s patients expect the full treatment. Explaining that more is not always better can be a tough sell.

It's our special look back over the entire decade which has Nathan and Laura firing on all fours. Not only do we discover their genomic highlights of the last ten years--ups and downs-- they also pull out their special "future glasses" and come up with a provocative list for the next ten. You don't want to miss this.

But first, we do cover December and that kerfuffle over the George Church dating app. And the genomics of income--really? Did you go for that?

Theral, Nathan, and Laura for an extended broadcast. Happy 2020!

You’re a mother, and life is typical. You’re also a pediatrician. Then one day you hear that your daughter is autistic. OK. Then you get the news that, no, it’s not autism but a very rare disease called Sanfilippo Syndrome. From your training as a pediatrician you quickly think back and remember the MPS rare diseases, but nothing else prepares you for what’s ahead.

Meet today’s guest, Cara O’Neill, who shortly after she learned the real diagnosis of her daughter, Eliza, together with her husband Glenn founded the Cure Sanfilippo Foundation out of their house by launching a viral video. Today the organization includes fifty families and funds research into treatments for the disease, including a gene therapy. Their daughter was patient number one.

Not only does the foundation work on a cure and other meaningful therapies, such as a program based on regenerative medicine, but they are also working to improve diagnosis. Currently diagnostic tests for Sanfilippo are not in any newborn screening panels. This is partly because the tests are just being developed, but there is activism work to do on the political front as well. States are not allowing the tests that are developed be included because there are no approved therapies.

“Requiring a therapy to institute newborn screening is ridiculous,” says Cara.

She knows many families who have three children by the time they know about their first child having the disease because of the problem of diagnostic delay.

“Maybe their first child gets diagnosed at age five. Then they have two more children and find out, gosh, they are affected too. They could have had more informed family planning decisions available to them had they known earlier.”

The MPS Society is a rare organization. Not just because it is an umbrella for the rare diseases that have in common lysosomal storage malfunction. But because it is one of the largest rare disease organizations in the world.

Terri Klein is the CEO leading the MPS Society. She says the group has over three thousand members on their roster. This brings some strength and resources in an area where low numbers intensifies an uphill battle.

Her job, she says, is to find those researchers out there working on the various MPS diseases--Hunter’s, Sanfillippo syndrome and about a dozen others--and make sure any and all science toward understanding, therapy and cures gets shared and developed. She "connects the dots" between research, funding, trial experts, parents and patients. Beyond the science and medicine, Terri says about half of her budget goes to care of patients.

So what is the state of existing therapies for these diseases now, and how close are we today to gene editing and gene therapy cures?

Terri has been instrumental in the creation of ConnectMPS, a very successful disease registry for MPS patients. What are her thoughts on how to make rare disease registers more impactful?

“I think the field has just really come to life over the last five or seven years. We’ve got all this sequence data. We’ve got the population data. We’ve got gene editing. I’ve been at this thirty plus years, and we haven’t had a culmination of technology and data like this before. I think everyone has to be excited in some way or other.”

Lon Cardon has lived through a few ups and downs in our field and remembers well the days when mention of his own area, statistical genetics, was the quickest way to kill a dinner conversation. The hype cycle has come full swing, and his days of pessimism have turned to full on optimism. Theral takes a couple stabs at it, but Lon’s giddiness is hard won.

Surely there are challenges, Theral argues. Have we become drunk on sequencing, as a recent guest commented? And what are the practical challenges Lon faces with big data? Aren’t there real hurdles?

We had some challenges of our own with Theral’s mic malfunctioning. But we're optimistic--the backup mic worked. We come in at around 23 1/2 minutes.

Presenting BioMarin’s new Chief Scientific Officer.

Matt Might came knocking on the door of genomic medicine out of pure necessity. After a four year diagnostic odyssey that led them to Duke University, Matt and his wife, Cristina, finally found out through exome sequencing that their son, Bertrand, was suffering from a rare disease known as NGLY1 deficiency. That was three years ago.

In today’s interview, we focus on what Matt did after he received this diagnosis. Through various means, mostly involving the internet, he has been able to connect with the parents of thirty seven other children with the same rare disease. As the group of patients grows, so do the options for studying the disease and for developing a therapy.

Since the president launched his Precision Medicine Initiative, we've heard from a new round of critics that genomics research just isn’t paying off. Matt’s story contradicts these criticisms.

In fact, he comes right out and says he’s on a campaign "to end the phrase, ‘non actionable.’” To Matt--who’s career has been in computer engineering--science is medicine. Matt’s connection with the rare disease community was kicked off with a personal blog he wrote that went viral, Hunting Down My Son’s Killer. Matt says with Google, blogging, and social media parents everywhere can do science. 

Prior to recording this interview, Matt was at the White House for a couple weeks helping out with the president’s new initiative. What is his take on that, and, as an outsider, what is the number one thing he would change about biomedical research?

Guest:

Liz Horn, PhD, Patient Advocate Bio and Contact Info

Listen (8:22) What is biobanking?

Listen (4:05) Sample collection and the diagnostic odyssey

Listen (5:45) Security and privacy concerns

Listen (2:46) The bigger picture

Patients with rare diseases are constantly pestered with sample collection. Blood and tissue samples are required for many different kinds of testing, and often the specialist clinicians or researchers do not connect and share with each other. Biobanks are an emerging solution for aggregating patient samples for research. As Dr. Liz Horn says in this interview, biobanks and disease registries have become an invaluable resource for both patients and those treating and studying them.

For more info, get the free eBook from Rare Genomics Institute

"Rare Disease Horizons: The Hope of New Research and Technology" is underwritten by the Rare Genomics Institute.

Guest: Mike Snyder, PhD, Director, Center for Genomics & Personalized Medicine, Stanford

Bio and Contact Info

Listen (6:30) What are the important omics other than genomics?

Listen (6:22) Now studying hundreds of millions of markers to get the complete picture

Listen (3:30) How can a patient benefit from this research?

Listen (1:38) What is the biggest research challenge?

Listen (3:23) Other omics already having an impact on cancer treatment

Genomics is often just the beginning to understanding any disease. There are many other biological mechanisms which are part of understanding disease pathways. Dr. Mike Snyder is perhaps the most biologically tracked man in the world. As part of a research project, he is regularly combing through his own biology, looking at over hundreds of millions of biomarkers on an ongoing basis. This includes his DNA, his proteins, his epigenome, and his microbiome among other ‘omes. Dr. Snyder gives an overview of the various omics which come in to play when understanding the complexity of the human body and disease.

For more info, get the free eBook from Rare Genomics Institute

"Rare Disease Horizons: The Hope of New Research and Technology" is underwritten by the Rare Genomics Institute.