(full disclosure: Sean Ekins is CSO at Phoenix Nest and consults with JJB as well as the Hereditary Neuropathy Foundation and Hannah’s Hope Foundation).
SE: Today I am happy to introduce Jill Wood. Jill, can you please tell us a bit about your background and what you do?
JW: I graduated from Oregon State University with a BS in retail management and apparel design. I am a rare disease patient advocate as my son Jonah was diagnosed with Sanfilippo syndrome in 2010. I co-founded Jonah’s Just Begun (JJB) a non-profit with my husband Jeremy Weishaar, to raise awareness and support those with Sanfilippo. I have been working on this 24/7 ever since. Last year I formed a company called Phoenix Nest to perform and fund research and development with our academic partners as well as ultimately commercialize treatments for this disease. I am also an active advocate for rare and ultra-rare diseases volunteering with the Rare Disease Legislative Advocates.
SE: Perhaps you can explain what Sanfilippo syndrome is please?
JW: Sanfilippo Syndrome is an ultra rare disease which can be described by four subtypes: A, B, C, and D. Jonah has Sanfilippo Syndrome subtype C, or Mucopolysaccharidosis III C is an autosomal recessive lysosomal storage disease (an ultra rare disease -14 Type C patients in the US) caused by deficiency of the enzyme heparan sulfate acetyl CoA: -glucosaminide N-acetyltransferase, (HGSNAT) responsible for degradation of heparan sulfate, a repeating carbohydrate generally found attached to proteoglycans.
Sanfilippo children look normal at birth but as the disease progresses the children develop mild coarse features and hair. They present with chronic sinus and ear infections attributing to speech delays. Other symptoms are: diarrhea, brittle teeth, bone deformities, enlarged tonsils, upper respiratory infections, seizures and hepatosplenomegaly. The disease progresses to increasing behavioral disturbances . Children ultimately become immobile and unresponsive, often requiring wheelchairs. They ultimately stop eating on their own and feeding tubes are required to prolong their lives. An affected child with Sanfilippo Syndrome type C commonly lives into their late twenties early thirties. There is no FDA approved treatment.
SE What is an ultra-rare disease
JW: Rare diseases are defined as those that affect fewer than 200,000 (prevalence less than or equal to 67/100,000, US) or fewer than 50,000 (prevalence 1/2000, UK). An ultra-rare disease affects substantially fewer patients, less than or equal to 6000 (prevalence 2/100,000, US). Unfortunately there is no official recognition of ultra-rare diseases.
SE: How rare is Sanfilippo Syndrome?
JW: Sanfilippo Syndrome is ultra rare..There are actually no figures for the USA but its 1 case per 280,000 live births in Northern Ireland, 1 per 66,000 in Australia, and 1 per 50,000 in the Netherlands.
There are probably 600 children with Type A, 300 with Type B, 80 with Type C and 80 with Type D in the USA.
SE: How many rare diseases are there and of those which have treatments?
JW: The National Organization for Rare Disorders (NORD) and state that there are only 250 treatments for the nearly 7,000 rare disorders, impacting 25-30 million Americans, while in contrast the FDA describes over 400 drugs and biologics developed for rare diseases.
SE: What research is going on for Sanfilippo syndrome?
JW: There are a couple of Clinical Trials For Sanfilippo Type A: Shire has a trial “Extension of Study HGT-SAN-055 Evaluating Administration of rhHNS in Patients With Sanfilippo Syndrome Type A (MPS IIIA.)”. Lysogene has a trial “Intracerebral Gene Therapy for Sanfilippo Type A Syndrome”.There are other companies pursuing Gene Therapy such as Esteve Biotech, “Novel gene therapy treatment for Sanfilippo Syndrome type A’, UniQure, “Novel gene therapy treatment for Sanfilippo Syndrome type B” and Abeona “Novel gene therapy treatment for type A and B”. Some are looking at Lentiviral Enhanced HSCT. An alternative to AAV and enzyme replacement therapy for MPSIII A&B. Brian Bigger at Manchester University in the UK is working on a AAV10 for Sanfilippo type C.
Small Molecule Research is also ongoing in several groups: Andrea Ballabio- TIGEM in Italy is working on Cellular Clearance, activation of TFEB (Transcription Factor EB). Alexey Pshezhetsky, Montreal Canada is pursuing Chaperone therapies for the missense mutation in Type C. and Pharmacological treatment to address pathophysiology of synaptic function for Sanfilippo C. Alessandro Fraldi, TIGEM in Italy is working on Lysosomal targeting in MPSIIIC. Daniel Grinberg University of Barcelona, Spain is looking at enzymatic increase with small molecules for the nonsense and splice site mutations. Brian Bigger is also studying Genistein a Substrate Optimizing Therapy. BioMarin has a Substrate Optimizing Therapy project too.
SE: So it would appear that most of the research for Sanfilippo syndrome is happening outside the USA?
JW: Yes, this is a problem for us as we have tried to submit NIH grants to fund researchers outside the USA and inside the USA. But the reviewers of such grants (based in the USA) appear to question the NIH rules in our justification for such research outside the USA. It means we have to continue to raise funds with our HANDS partners (Sanfilippo Barcelona, Spain; Sanfilippo France; Sanfilippo Portugal and JLK Sanfilippo Research Foundation) to fund most of this research.
We will submit a grant with Dr. Patricia Dickson and her colleagues at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center so we will see how this fares.
SE: What other competitive sources of funding have you tried?
In December 2012 we entered a proposal in the “BeHeard rare disease challenge” run by Assay Depot and the Rare Genomics Institute (http://raregenomics.org/) to generate a Knock out (KO) mouse for Type D. Sanfilippo Syndrome subtype D, or Mucopolysaccharidosis III D is an autosomal recessive lysosomal storage disease caused by the deficiency of the enzyme N-acetylglucosamine-G-sulfate sulfatase which is needed to break down the glycosaminoglycan heparan sulfate. We think that out of the 4 types of Sanfilippo, type D is in the best position for an effective treatment. Type D is also a relatively mild form of the disease compared to Types A, B and C. It is hypothesized that with just a small increase in enzymatic activity, the disease could be drastically improved. A mouse model of the disease and a better understanding of the brain pathology of the disease, will assist us in developing a treatment. It is JJB’s aim to champion Type D research (alongside that of Type C), using our consortium of investigators to test treatments that we are already funding for type C and translate them and test them for type D. We recently learned that we were successful and had won the KO mouse development prize! The press release came out from Taconic who will kindly develop the mouse and donate it to us.
We actually submitted two proposals and we won part of what we had requested to help support our collaborations to find small molecule treatments for Type C. The judges awarded us the CDD Vault prize, so we are looking forward to putting that into action with our scientists and getting them to share their results securely!!
SE: What other approaches do you use to fund research?
We have many fundraisers organized by ourselves and our dear friends which include 2 wine tasting events, 2 Charity Bazaars, Bunco Parties, Walk-a-than, Golfing events, online fundraisers and donations through the JJB website. Besides these fundraisers we are fortunate to have supporters who do extraordinary things like Erik DeAngelis who is doing a sponsored triathlon in November and the actor Jonny Lee Miller who raised money and awareness for the disease via crowdfunding for his sponsored ultramarathon.
SE: When I met you first at Partnering for Cures in 2011 I was impressed with how much you had done in such a short space of time as someone with little scientific background. Can you summarize what you have done for JJB because I think this will inspire other parents when they receive a diagnosis that their child has a rare disease?
JW: You have to understand I have no scientific background, not even a little bit !!
So I first searched the web and found PubMed and then found some of the key researchers in the field. One of these was Dr. Alexey Pshezhetsky (Canada). By September 2010 JJB made the first grant to Alexey Pshezhetsky for his work on chaperone therapy. I also met the clinician Dr.Wendy Chung who offered to advise JJB, from there we built our scientific advisory board (SAB). This consisted of Wendy Chung (Columbia/Presbyterian), Maryam Banikazemi (Columbia/Presbyterian), Robert Steiner (OHSU), Greg Pastores (NYU) and Sandra Ctarina Concicao Alves (INSA, Portugal.). The SAB gave JJB a plan of action: build the patient population, get the Natural History Study under way and identify the science for Sanfilippo. We built our patient population by immediately networking with the other Mucopolysaccharidosis (MPS) organizations, creating a website (https://jonahsjustbegun.org/), blog (http://jonahsjustbegun.blogspot.com/), and Facebook page (http://www.facebook.com/pages/Jonahs-Just-Begun-Foundation-to-Cure-Sanfilippo-Inc/132452613432013). I then went on a media blitz appearing on several local NYC news stations and National Program; Good Morning America. Articles in the Daily News and Metro News brought JJB the TV coverage. From the media exposure I found a handful more Sanfilippo type C cases. The like-minded parents came together and formed JJB’s director’s board. Since the patient population is so small in the US (18) JJB branched out and went global. The first patient population meeting took place in France, where I met with Portuguese, French and Spanish families. Together the families with the aid of translators, laid out a game plan. Jeremy and I on the advice of the SAB started attending genetic conferences focused on Lysosmal Storage Disease’s. The conferences gave us a chance to meet and connect with world leading scientists investigating Sanfilippo: besides Dr. Alexey Pshezhetsky we also met Dr. Brian Bigger (UK), Dr. Frits Wijburg (Netherlands), Dr.Simon Jones (UK), Dr. Andrea Ballabio (TGIM), Dr. Alessandro Fraldi (TGIM), Dr. Daniel Grinberg (Barcelona), Dr. Haiyan Fu (OH), Dr. Ed Wraith (UK), Dr.Gregor Wegrzyn (Poland), Dr. John Hopwood (Australia) and Dr. Steven Walkley (Albert Einstin). I also established relationships with prominent clinicians following Sanfilippo children: Dr. Maria Escolar, Dr. Elsa Shapiro and Dr. Chet Whitley.
In April of 2011, JJB hosted a patient population meeting in NY. I identified three scientists focused on MPSIIIC that were ready and willing, chaired by JJBs NY SAB members: Dr. Wendy Chung, Dr. Myriam Banikazemi and Dr. Greg Pastores. In attendance were several parents from Europe and the US. My clinician Dr. Maria Escolar joined as well. Together they brain stormed on appropriate, feasible and timely treatment options for MPSIIIC. With Chaperone therapy already in the works for common missense mutations, they focused on the common splice site mutations found in our European friends. For a universal approach they all agreed that gene therapy with an AAV would be our closest option that would benefit all MPSIIIC children. While I waited for the Type C mouse model to colonize. JJB drafted a contract with Dr. Alexey Pshezhetsky and Dr. Brian Bigger to start the work for the first ever treatment of MPSIIIC, Gene Therapy. By October 2011 the mice were ready. With the help of JJB’s sister foundations we began funding a gene therapy. I have also been working on raising funds for a Natural History Study. JJB has identified a P.I. Paul Levy at Childrens Hospital of Montifore. Over the course of three years between traveling Europe and the US connecting investigators and families, JJB has managed to raise over $500,000. This has gone to funding chaperone research, gene therapy, novel nanopartical vectors, iSP Neuronal MPSIIIC model and a study on our Splice-Site Mutations. Other monies have been allocated to JJB’s patient population meetings and helping other Sanfilippo families receive care from Sanfilippo specialists.
I have connected with parents and clinicians at several MPS conferences. Geneva, UK (twice) France, Portugal, Vegas, Italy, Spain, New York, and held mini patient population meetings. I have attended conferences such as Genetic Alliance, Partnering for Cures, WORLD and ASHG. I have also had two speaking engagements at Columbia/Presbyterian where I shared with an auditorium full of med students my story and efforts to drive science and raise awareness for Sanfilippo Syndrome. Similarly in 2012 at Partnering for cures I presented with you in New York. I also presented at the 2012 Global Genes summit.
To date, JJB and our HANDS partners have initiated 5 preclinical research projects and work closely with 7 laboratories in Canada and across Europe. We have made small grants to academic researchers ($20,000) that have been helpful as they provide seed funding for projects (e.g. to fund a postdoc) that can then lead to securing larger grants. For example, JJB initiated chaperone therapy using the first ever knock out mouse for Type C (also funded by the Canadian Institutes of Health Research), which has given us invaluable insight into the disease progression.
SE: When we first met I think the second thing that you impressed upon me was the sense of urgency, the clock was ticking to help Jonah. As scientists removed so far from the patient I think we miss out on that but every day you get to experience a rare disease and see how it impacts your family. What do you think we should be doing as scientists to help you?
JW:For a start we need to keep raising the profile of rare diseases so the funding situation can improve. Compared to the money, resources and the decades of research that has gone into drug discovery for multi-gene defect diseases like Alzheimer’s disease (2010 NIH funding $469 million), Multiple Sclerosis (2011 NIH funding $122 million) and Parkinson’s Disease (2011 NIH funding $151 million), relatively little has been invested in the USA for Sanfilippo syndrome research compared to these diseases. And of course compared to funding for Cancer and HIV/AIDS, rare disease funding pales in comparison.
Second, I think getting more scientists involved in the basic research behind rare diseases would be a good thing. The increased visibility of rare diseases from mid-size biotechs and big pharma’s getting involved, the controversy over funding such treatments and some high profile successes (Vertex and their cystic fibrosis treatment) have all served to raise awareness. This is our moment in the limelight and if we do not seize it and do something positive with it we will just be another footnote in the history of drug discovery and development (like combinatorial chemistry, systems biology and biomarkers!).
SE: The third impression of JJB (perhaps rare diseases in general) was that you would be a direct beneficiary of a more collaborative approach to drug discovery.
JW: Yes as a parent, I can do and say things that perhaps another scientist would have difficulty with. As a desperate parent I can impact legislators to provide more funding for the NIH and FDA. I can be forward, I can suggest people work together, share what they are doing and collaborate. We all want to see some success. I want to cure Jonah and his friends, the scientist wants to publish and have priority, I want to help them be successful. I am an advocate for the scientists as much as the disease because without them there would be really no hope. As a parent I keep my rare disease community informed, inspire them to fight and encourage them to participate in registries, NHS and trials.
SE: And yet, you strike me as someone that could roll up your sleeves and get in the lab, have you ever felt like you wanted to do that to literally make the science move faster?
I daydream about what my scientists are doing in the lab everyday. I don’t see myself looking through a microscope analyzing the synaptic functions of a mouse brain. But I would make coffee runs for the team, answer the phones for them, go grocery shopping for them… Whatever they needed I’d do it. This past June I met up with several European MPSIII families for our annual PPM. Our PI’s at the Telethon Institute in Italy hosted us. We were given a tour of IGEM’s lab, I can’t even begin to describe how awesome it was to see my P.I’s. Alessandro Fraldi and Andrea Ballabio’s work space and meat their entire lab members. The experience was priceless, now I can actually visualize these men and women at work for our kids Monday-Friday 8 hours a day. We left our scientists with pictures of our children to hang up in the lab, it feels good knowing that they see me son’s smiling face everyday at work.
SE: You are a small organization which literally is run from your kitchen in Brooklyn how did you get involved in lobbying Congress on rare diseases?
JW: A friend introduced me to Julia Jenkins at RDLA, she invited me to get involved to have language added to Prescription Drug User Fee Act (PADUFA). The legislation was introduced to Congress as the “ULTRA -act” and then a revised version “FAST” was introduced 1st March 2012. The points that I specifically lobbied to have added to PADUFA, will accelerate FDA approval for clinical trials for rare diseases.
Then I joined RDLA and 200 rare disease advocates in Washington, DC to honor Rare Disease Day this past February. We had five main goals:
- Educate patient advocates about the legislative and appropriations process
- Inform Congress about rare diseases and the many different needs of the patient community
- Build lasting relationships with members of Congress and their staff
- Ensure that the needs of rare disease patients are considered in future legislation and policy
- Empower patient advocates to take an active role in the democratic process
SE: I think you represent a triple threat: part citizen scientist, part advocate and part entrepreneur, which role do you enjoy most?
None of them. I don’t want to be doing this. This isn’t the life I had planed for me and my family. I want to be like most everyone else, taking my kids to swim practice, helping them on their homework, saving for their college educations. Yet here I am, I have to save my son’s life and now hundreds of other Sanfilippo families are counting on me as well.
SE: You inspired Alex Clark and myself to develop the ODDT mobile app. How have you embraced technologies and social media.
JW: I am an active user of social media (Twitter, Facebook and email blasts) asking supporters of JJB to call their congress person, to support the rare disease caucus and other important agendas of the rare disease community. We even had a flashmob to celebrate rare disease day. I will pretty much do anything we can to increase visibility for the cause and all of these social media and various technologies play their part. I do think the scientists I work with lag behind in using social media, perhaps mobile technologies like ODDT could change that, but in the meantime the patients and parents can benefit from data and important links on the rare diseases being more easy to find.
SE: What has JJB been doing in recent months?
We’re currently working with other Sanfilippo organizations to collectively launch a patient registry with PatientCrossroads for all types of Sanfilippo, which will help us identify patients with the disease. In addition we will also launch the MPSIIIC natural history study at The Children’s hospital of Montefiore, which will help us characterize the disease in patients. We have been working with a new web designer to maximize our visibility, using social media. We’re gearing up for Jonny Lee Miller’s 2nd ultra-marathon that he is running to help raise funds for our medical research. Jonny uses Twitter to send people to our site and his crowdrise fundraiser. We’re busy promoting Jonny’s run and Erik’s triathlon. Now that our science is moving full speed ahead I can breathe easier on that part. Now it’s time to focus on raising funds to keep that science going.
SE: I recognized a similar ability in yourself and two other parent / patient advocates I had met through you. You are all well respected by the scientists you work with as a peer, is this something we will see more often, parents driving the science?
Lori Sames (Hannah’s Hope Fund), Allison Moore (Hereditary Neuropathy Foundation) are my peers and have been working in rare diseases for longer. Both of them started their not for profits before I did. We do share a common bond, we all immerse ourselves in the fundraising, the science and networking with the groups that are going to help our causes and efforts to find treatments. I hope we can pass this desire for more knowledge on our diseases on to others and inspire them too. A diagnosis of a rare disease for themselves or a child is definitely a life changing experience but we can make a positive difference, we can raise money so we will ultimately know more about these diseases.
I hope more parents / advocates can get involved with the science because we offer a unique perspective, we humanize the science and with us around I think the scientists communicate more clearly what they are doing. I think they also see us as a much needed potential source of funding and support. We certainly do tell all our networks about exciting science we see very quickly, so their science has an audience that is eagerly awaiting the next publication.
SE: You recently became an author of a scientific paper with Allison and Lori and myself, how does that feel as a first time author?
When Jonah was first diagnosed I spent hours searching through Pubmed. I still check it weekly. To have my name come up on a google search is like… being famous. I earned my title “citizen scientists.” lol
SE: That’s probably as good as any way to conclude, I want to thank you for sharing your inspiring experiences as a parent, a citizen scientist, a co-founder of a scientific foundation and a CSO of a rare disease company and very much look forward to hearing more from you in the future.
Thank you .
